A simple approach to estimate daily loads of total, refractory, and labile organic carbon from their seasonal loads in a watershed

Treesearch

Ying Ouyang; Johnny M. Grace; Wayne C. Zipperer; Jeff Hatten; Janet Dewey

2018-01-01

Loads of naturally occurring total organic carbons (TOC), refractory organic carbon (ROC), and labile organic carbon (LOC) instreams control the availability of nutrients and the solubility and toxicity of contaminants and affect biological activities throughabsorption of light and complex metals with production of carcinogenic compounds....

Ductile mandrel and parting compound facilitate tube drawing

NASA Technical Reports Server (NTRS)

Burt, W. R., Jr.; Mayfield, R. M.; Polakowski, N. H.

1966-01-01

Refractory tubing is warm drawn over a solid ductile mandrel with a powder parting compound packed between mandrel and the tubes inner surface. This method applies also to the coextrusion of a billet and a ductile mandrel.

Friction and wear of radiofrequency-sputtered borides, silicides, and carbides

NASA Technical Reports Server (NTRS)

Brainard, W. A.; Wheeler, D. R.

1978-01-01

The friction and wear properties of several refractory compound coatings were examined. These compounds were applied to 440 C bearing steel surfaces by radiofrequency (RF) sputtering. The refractory compounds were the titanium and molybdenum borides, the titanium and molybdenum silicides, and the titanium, molybdenum, and boron carbides. Friction testing was done with a pin-on-disk wear apparatus at loads from 0.1 to 5.0 newtons. Generally, the best wear properties were obtained when the coatings were bias sputtered onto 440 C disks that had been preoxidized. Adherence was improved because of the better bonding of the coatings to the iron oxide formed during preoxidation. As a class the carbides provided wear protection to the highest loads. Titanium boride coatings provided low friction and good wear properties to moderate loads.

Synthesis, Structure, and Properties of Refractory Hard-Metal Borides

NASA Astrophysics Data System (ADS)

Lech, Andrew Thomas

As the limits of what can be achieved with conventional hard compounds, such as tungsten carbide, are nearing reach, super-hard materials are an area of increasing industrial interest. The refractory hard metal borides, such as ReB2 and WB4, offer an increasingly attractive alternative to diamond and cubic boron nitride as a next-generation tool material. In this Thesis, a thorough discussion is made of the progress achieved by our laboratory towards understanding the synthesis, structure, and properties of these extremely hard compounds. Particular emphasis is placed on structural manipulation, solid solution formation, and the unique crystallographic manifestations of what might also be called "super-hard metals".

Clinical and Electrocardiographic Characteristics of Electrical Storms Due to Monomorphic Ventricular Tachycardia Refractory to Intravenous Amiodarone.

PubMed

Murata, Hiroshige; Miyauchi, Yasushi; Hayashi, Meiso; Iwasaki, Yu-Ki; Yodogawa, Kenji; Ueno, Akira; Hayashi, Hiroshi; Tsuboi, Ippei; Uetake, Shunsuke; Takahashi, Kenta; Yamamoto, Teppei; Maruyama, Mitsunori; Akutsu, Koichi; Yamamoto, Takeshi; Kobayashi, Yoshinori; Tanaka, Keiji; Atarashi, Hirotsugu; Katoh, Takao; Shimizu, Wataru

2015-01-01

Few reports are available on the characteristics of electrical storms of ventricular tachycardia (VT storm) refractory to intravenous (IV) amiodarone. IV-amiodarone was administered to 60 patients with ventricular tachyarrhythmia between 2007 and 2012. VT storms, defined as 3 or more episodes of VT within 24 h, occurred in 30 patients (68±12 years, 7 female), with 12 having ischemic and 18 non-ischemic heart disease. We compared the clinical and electrocardiographic characteristics of the patients with VT storms suppressed by IV-amiodarone (Effective group) to those of patients not affected by the treatment (Refractory group). IV-amiodarone could not control recurrence of VT in 9 patients (30%). The Refractory group comprised 5 patients with acute myocardial infarctions. Although there was no difference in the VT cycle length, the QRS duration of both the VT and premature ventricular contractions (PVCs) followed by VT was narrower in the Refractory group than in the Effective group (140±30 vs. 178±25 ms, P<0.01; 121±14 vs. 179±22 ms, P<0.01). In the Refractory group, additional administration of IV-mexiletine and/or Purkinje potential-guided catheter ablation was effective. IV-amiodarone-refractory VT exhibited a relatively narrow QRS tachycardia. The narrow triggering PVCs, suggesting a Purkinje fiber origin, may be treated by additional IV-mexiletine and endocardial catheter ablation.

Melatonin and childhood refractory epilepsy--a pilot study.

PubMed

Paprocka, Justyna; Dec, Renata; Jamroz, Ewa; Marszał, Elzbieta

2010-09-01

The aim of the study was to assess diurnal melatonin secretion in children with refractory epilepsy (N=74) as compared to children without epileptic seizures (N=37) and to compare melatonin secretion in children with focal and generalized refractory epilepsy. In the study group 4 subgroups were defined: children with focal symptomatic epilepsy, focal cryptogenic epilepsy, generalized symptomatic epilepsy, and generalized cryptogenic epilepsy. Melatonin level was measured every 3 hours using the RIA method. Analysis of diurnal melatonin secretion indicated a lower level of the hormone in patients with refractory epilepsy. The daily rhythm of melatonin secretion in the study group was maintained, with a peak shift of melatonin secretion especially visible in the subgroup with generalized symptomatic refractory epilepsy in the age group between 6 months and 3 years of age. The hypothesis may be formed that a lowered level of melatonin in the study group in relation to the comparison group is the consequence of the natural course of epilepsy or is influenced by antiepileptic drugs.

The friction and wear properties of sputtered hard refractory compounds

NASA Technical Reports Server (NTRS)

Brainard, W. A.

1978-01-01

Several refractory silicide, boride, and carbide coatings were examined. The coatings were applied to type 440C steel surfaces by radio-frequency sputtering. The friction and wear properties of the coatings were found to be related to stoichiometry and impurity content of the bulk coating as well as the degree of interfacial adherence between coating and substrate. Bulk coating stoichiometry could to a large extent be controlled by the application of a negative bias voltage during deposition. Adherence was promoted by the formation of an oxidized layer at the interface. Deliberate preoxidizing of the 440C produced enhanced adherence for many compounds which are related to the formation of a mixed oxide transition region.

40 CFR 442.2 - General definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., organic chemicals including: alcohols, aldehydes, formaldehydes, phenols, peroxides, organic salts, amines..., glycerines, and organic polymers; refractory organic compounds including: ketones, nitriles, organo-metallic...

Emission spectrometric arcing procedure with minimal effect of chemical form of sample. [performed on refractory metal matrix composites

NASA Technical Reports Server (NTRS)

Gordon, W. A.

1975-01-01

Matrix effects related to the chemical form of analyzed materials were studied. An arc in argon was used which was buffered with silver chloride. The effect of chemical form was minimal for a variety of metals, oxides, and carbides representing the most refractory compounds and thermally stable metal-containing molecules. Only four of the most refractory materials known showed significant emission depressions due to incomplete volatilization in the arc system. These results are discussed in terms of vapor pressures of the solid materials placed on the anodes and dissociation reactions of the molecules in the gaseous environment.

Biodesulfurization of refractory organic sulfur compounds in fossil fuels.

PubMed

Soleimani, Mehran; Bassi, Amarjeet; Margaritis, Argyrios

2007-01-01

The stringent new regulations to lower sulfur content in fossil fuels require new economic and efficient methods for desulfurization of recalcitrant organic sulfur. Hydrodesulfurization of such compounds is very costly and requires high operating temperature and pressure. Biodesulfurization is a non-invasive approach that can specifically remove sulfur from refractory hydrocarbons under mild conditions and it can be potentially used in industrial desulfurization. Intensive research has been conducted in microbiology and molecular biology of the competent strains to increase their desulfurization activity; however, even the highest activity obtained is still insufficient to fulfill the industrial requirements. To improve the biodesulfurization efficiency, more work is needed in areas such as increasing specific desulfurization activity, hydrocarbon phase tolerance, sulfur removal at higher temperature, and isolating new strains for desulfurizing a broader range of sulfur compounds. This article comprehensively reviews and discusses key issues, advances and challenges for a competitive biodesulfurization process.

Gas atomization synthesis of refractory or intermetallic compounds and supersaturated solid solutions

DOEpatents

Anderson, Iver E.; Lograsso, Barbara K.; Ellis, Timothy W.

1994-01-01

A metallic melt is atomized using a high pressure atomizing gas wherein the temperature of the melt and the composition of the atomizing gas are selected such that the gas and melt react in the atomization spray zone to form a refractory or intermetallic compound in the as-atomized powder particles. A metallic melt is also atomized using a high pressure atomizing gas mixture gas wherein the temperature of the melt and the ratio of a reactive gas to a carrier gas are selected to form powder particles comprising a supersaturated solid solution of the atomic species of the reactive gas in the particles. The powder particles are then heat treated to precipitate dispersoids in-situ therein to form a dispersion strengthened material.

Combined application of alginate dressing and human granulocyte-macrophage colony stimulating factor promotes healing in refractory chronic skin ulcers.

PubMed

Huang, Guobao; Sun, Tangqing; Zhang, Lei; Wu, Qiuhe; Zhang, Keyan; Tian, Qingfen; Huo, Ran

2014-06-01

The aim of the present study was to evaluate the clinical therapeutic effect of the combined application of alginate and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the healing of refractory chronic skin ulcers. A single center, three arm, randomized study was performed at Jinan Central Hospital (Jinan, Shandong, China). A total of 60 patients with refractory chronic skin ulcers, which persisted for >1 month, were enrolled and randomly assigned into one of the following three groups: alginate dressing/rhGM-CSF group (group A), rhGM-CSF only group (group B) and conventional (vaseline dressing) group (group C). The wound area rate was measured, granulation and color were observed and pain was evaluated. The data were summarized and statistical analysis was performed. The results demonstrated that group A exhibited a significantly faster wound healing rate and lower pain score compared with the other groups (P<0.01). In conclusion, the combined application of alginate dressing and rhGM-CSF for the treatment of refractory chronic skin ulcers demonstrated significant advantages. It promoted the growth of granulation tissue, accelerated re-epithelialization and also effectively reduced wound pain, and thus improved the quality of life for the patient. This suggests that the combined application of alginate and rhGM-CSF may be an effective therapeutic strategy for the clinical treatment of refractory chronic skin ulcers.

[Pharmacologic action profile of crataegus extract in comparison to epinephrine, amirinone, milrinone and digoxin in the isolated perfused guinea pig heart].

PubMed

Joseph, G; Zhao, Y; Klaus, W

1995-12-01

Using isolated perfused guinea pig hearts experiments were performed to investigate the influence of crataegus extract LI 132 (Faros 300, CRA) in comparison to other inotropic drugs--epinephrine (adrenaline, ADR), amrinone (AM), milrinone (MIL) and digoxin (DIG)--on different functional parameters, with special emphasis on the effective refractory period of the myocardium. The simultaneous registration of appropriate parameters allowed to relate the effect on the refractory period to the inotropic, chronotropic, dromotropic and coronary actions of these compounds at each concentration level. All substances--with the exception of CRA--shortened the effective refractory period concentration-dependently besides their known other functional effects (max.: 1 x 10(-5) mol/l ADR by 38%, 7 x 10(-7) mol/l DIG by 26%, 1 x 10(-4) mol/l MIL by 13% and 5 x 10(-4) mol/l AM by 1.6%). Related to the positive inotropy the shortening was most effective under MIL (1.32 ms/mN), followed by AM (0.65 ms/mN), DIG (0.40 ms/mN) and ADR (0.28 ms/mN). On the contrary, CRA produced a prolongation of the effective refractory period by maximally 10% resp. by 2.54 ms/mN. Thus, the pharmacologic profile of CRA differs from that of other inotropic compounds mainly in this parameter (with potentially reduced arrhythmogenic risk).

Gas atomization synthesis of refractory or intermetallic compounds and supersaturated solid solutions

DOEpatents

Anderson, I.E.; Lograsso, B.K.; Ellis, T.W.

1994-11-29

A metallic melt is atomized using a high pressure atomizing gas wherein the temperature of the melt and the composition of the atomizing gas are selected such that the gas and melt react in the atomization spray zone to form a refractory or intermetallic compound in the as-atomized powder particles. A metallic melt is also atomized using a high pressure atomizing gas mixture gas wherein the temperature of the melt and the ratio of a reactive gas to a carrier gas are selected to form powder particles comprising a supersaturated solid solution of the atomic species of the reactive gas in the particles. The powder particles are then heat treated to precipitate dispersoids in-situ therein to form a dispersion strengthened material. 9 figures.

Photocatalytic Oxidation of Oil Contaminated Water Using TiO2/UV

NASA Astrophysics Data System (ADS)

Vargas Solla, Monica; Romero Rojas, Jairo

2017-04-01

Currently, oil is one of the most used energy sources all around the world, for example to make motor engines work. That prevailing usage of oil is the reason why water sources are under serious pollution risks with compounds that are hard to remove, such as hydrocarbons. There are a few water treatment processes known as Advanced Oxidation Processes, which search for a way to treat polluted water with toxic refractory compounds, to make its reuse more feasible and to avoid or at least appease the injurious effects of pollution over ecosystems. A heterogeneous photocatalysis water treatment technology, sorted as an Advanced Oxidation Process, which is intended to treat refractory compound polluted water by the use of TiO2 and UV light, is presented in this investigation. The evidence about its efficiency in hydrocarbon removal from used motor oil polluted water, since it is an extremely important pollutant due to its complexity, toxicity and recalcitrant characteristics, is also presented through COD, Oil and Grease and Hydrocarbons analysis.

Molecular-level dynamics of refractory dissolved organic matter

NASA Astrophysics Data System (ADS)

Niggemann, J.; Gerdts, G.; Dittmar, T.

2012-04-01

Refractory dissolved organic matter (DOM) accounts for most of the global oceanic organic carbon inventory. Processes leading to its formation and factors determining its stability are still largely unknown. We hypothesize that refractory DOM carries a universal molecular signature. Characterizing spatial and temporal variability in this universal signature is a key to understanding dynamics of refractory DOM. We present results from a long-term study of the DOM geo-metabolome in the open North Sea. Geo-metabolomics considers the entity of DOM as a population of compounds, each characterized by a specific function and reactivity in the cycling of energy and elements. Ten-thousands of molecular formulae were identified in DOM by ultrahigh resolution mass spectrometry analysis (FT-ICR-MS, Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry). The DOM pool in the North Sea was influenced by a complex interplay of processes that produced, transformed and degraded dissolved molecules. We identified a stable fraction in North Sea DOM with a molecular composition similar to deep ocean DOM. Molecular-level changes in this stable fraction provide novel information on dynamics and interactions of refractory DOM.

THERMAL DECOMPOSITION OF URANIUM COMPOUNDS

DOEpatents

Magel, T.T.; Brewer, L.

1959-02-10

A method is presented of preparing uranium metal of high purity consisting contacting impure U metal with halogen vapor at between 450 and 550 C to form uranium halide vapor, contacting the uranium halide vapor in the presence of H/sub 2/ with a refractory surface at about 1400 C to thermally decompose the uranium halides and deposit molten U on the refractory surface and collecting the molten U dripping from the surface. The entire operation is carried on at a sub-atmospheric pressure of below 1 mm mercury.

The efficacy and safety of pomalidomide in relapsed/refractory multiple myeloma in a "real-world" study: Polish Myeloma Group experience.

PubMed

Charlinski, Grzegorz; Grzasko, Norbert; Jurczyszyn, Artur; Janczarski, Mariusz; Szeremet, Agnieszka; Waszczuk-Gajda, Anna; Bernatowicz, Paweł; Swiderska, Alina; Guzicka-Kazimierczak, Renata; Lech-Maranda, Ewa; Szczepaniak, Andrzej; Wichary, Ryszard; Dmoszynska, Anna

2018-06-08

Patients with relapsed/refractory multiple myeloma (RRMM) have poor prognosis. Pomalidomide is an immunomodulatory compound that has demonstrated activity in MM patients with disease refractory to lanlidomide and bortezomib. Participants of clinical trials are highly selected populations; therefore, the aim of this study was to present observations from real practice that might provide important information for practitioners. We analyzed retrospectively 50 patients treated with pomalidomide in 12 Polish sites between 2014 and 2017. Median age was 63 years, median time since diagnosis 4.5 years and median number of prior regimens 4. The overall response rate was 39.1%. Median progression-free survival (PFS) and overall survival (OS) were 10.0 and 14.0 months, respectively. Previous treatment with immunomodulatory drugs, bortezomib or stem cell transplant had no impact on PFS and OS. Most frequent grade 3/4 treatment-emergent adverse events were hematologic (neutropenia 24.0%, thrombocytopenia 10.0%, anemia 8.0%). Most common grade 3/4 non-hematologic toxicities were respiratory tract infection (14.0%) and neuropathy (4.0%). This real-world data have confirmed that pomalidomide is an active drug in RRMM and support results of published clinical trials and other real-world studies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Comparison of cytokines and prooxidants/antioxidants markers among adults with refractory versus well-controlled epilepsy: A cross-sectional study.

PubMed

Ethemoglu, Ozlem; Ay, Halil; Koyuncu, Ismail; Gönel, Ataman

2018-06-15

This study aims to investigate the serum adiponectin, interleukin (IL)-6 and oxidative stress in epilepsy patients who are refractory or non-refractory to treatments. The study comprised 31 refractory epilepsy, 29 well-controlled epilepsy patients and control group including 29 healthy individuals. The serum adiponectin, IL-6, total antioxidant status (TAS), total oxidant status levels (TOS) and oxidative stress index (OSİ) were determined. The mean serum adiponectin and TAS levels were significantly lower in the refractory epilepsy patients than in the healty controls, and mean IL-6, TOS and OSİ levels were significantly higher. The serum adiponectin, IL-6, TAS, TOS and OSI levels were not significantly different between the well-controlled epilepsy patients and the healthy controls. The mean serum IL-6 and oxidative stress levels in refractory epilepsy patients were higher and the serum adiponectin level was lower than the healthy control group. These findings may be associated with an increased risk of seizures, atherosclerosis and cardiovascular disease in refractory epilepsy patients. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Refractory inclusions in the Ornans C30 chondrite

NASA Technical Reports Server (NTRS)

Davis, A. M.

1985-01-01

Several types of metedorites contain unusual objects 10 micrometers to 2 centimeters across that are enriched in refractory elements such as calcium, aluminum and titanium. These objects, commonly known as refractory inclusions, are most abundant in the meteorites known as carbonaceous chondrites. The refractory inclusions that have been found in the Ornans metedorite, a member of a little-studied group of carbonaceous chondrites are described. Some refractory inclusions in Ornans resemble those found in other meteorites, while others are unlike any seen before. The unusual inclusions in Ornans contain minerals with extraordinary enrichments in highly refractory elements.

Synthesis of refractory materials

DOEpatents

Holt, Joseph B.

1984-01-01

Refractory metal nitrides are synthesized during a combustion process utilizing a solid source of nitrogen. For this purpose, a metal azide is employed. The azide is combusted with a transition metal of the IIIB, IVB group, or a rare earth metal, and ignited to produce the refractory material.

Synthesis of refractory materials

DOEpatents

Holt, J.B.

Refractory metal nitrides are synthesized during a combustion process utilizing a solid source of nitrogen. For this purpose, a metal azide is employed. The azide is combusted with a transition metal of the IIIB, IVB group, or a rare earth metal, and ignited to produce the refractory material.

A study on the efficacy of rebamipide for patients with proton pump inhibitor-refractory non-erosive reflux disease.

PubMed

Adachi, Kyoichi; Furuta, Kenji; Miwa, Hiroto; Oshima, Tadayuki; Miki, Masaharu; Komazawa, Yoshinori; Iwakiri, Katsuhiko; Furuta, Takahisa; Koike, Tomoyuki; Shimatani, Tomohiko; Kinoshita, Yoshikazu

2012-06-01

Reflux symptoms in patients with non-erosive reflux disease (NERD) cannot be easily controlled by treatment with proton pump inhibitors (PPI). The anti-inflammatory function of rebamipide may be effective for protecting the esophageal mucosa. This prospective randomized multicenter placebo-controlled study was performed to clarify the efficacy of rebamipide for NERD patients whose reflux symptoms were refractory to PPI treatment. One hundred forty-nine patients were enrolled on the basis of a QUEST score of over 6 and absence of endoscopically proven esophageal mucosal breaks. All the patients were initially administered 15 mg of lansoprazole for 4 weeks, and the symptoms were then assessed using QUEST and GSRS. PPI-refractory patients were randomly assigned to administration of rebamipide or placebo t.i.d. for 4 weeks. Three of the 149 patients were lost to follow-up, and 60 among the remaining 146 patients were found to be PPI-refractory. Among these PPI-refractory patients, 31 were randomly assigned to a rebamipide group and 29 to a placebo group. At the end of drug administration, the QUEST and GSRS scores did not differ between the rebamipide and placebo groups, although a significantly higher proportion of patients in the rebamipide group showed amelioration of abdominal pain and diarrhea. Administration of rebamipide cannot effectively control reflux symptoms in NERD patients whose symptoms are refractory to PPI therapy.

Novel, broad-spectrum anticonvulsants containing a sulfamide group: pharmacological properties of (S)-N-[(6-chloro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]sulfamide (JNJ-26489112).

PubMed

McComsey, David F; Smith-Swintosky, Virginia L; Parker, Michael H; Brenneman, Douglas E; Malatynska, Ewa; White, H Steve; Klein, Brian D; Wilcox, Karen S; Milewski, Michael E; Herb, Mark; Finley, Michael F A; Liu, Yi; Lubin, Mary Lou; Qin, Ning; Reitz, Allen B; Maryanoff, Bruce E

2013-11-27

Broad-spectrum anticonvulsants are of considerable interest as antiepileptic drugs, especially because of their potential for treating refractory patients. Such "neurostabilizers" have also been used to treat other neurological disorders, including migraine, bipolar disorder, and neuropathic pain. We synthesized a series of sulfamide derivatives (4-9, 10a-i, 11a, 11b, 12) and evaluated their anticonvulsant activity. Thus, we identified promising sulfamide 4 (JNJ-26489112) and explored its pharmacological properties. Compound 4 exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically induced, and chemically induced seizures. Mechanistically, 4 inhibited voltage-gated Na(+) channels and N-type Ca(2+) channels and was effective as a K(+) channel opener. The anticonvulsant profile of 4 suggests that it may be useful for treating multiple forms of epilepsy (generalized tonic-clonic, complex partial, absence seizures), including refractory (or pharmacoresistant) epilepsy, at dose levels that confer a good safety margin. On the basis of its pharmacology and other favorable characteristics, 4 was advanced into human clinical studies.

Novel, Broad-Spectrum Anticonvulsants Containing a Sulfamide Group: Pharmacological Properties of (S)-N-[(6-Chloro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]sulfamide (JNJ-26489112)

PubMed Central

McComsey, David F.; Smith-Swintosky, Virginia L.; Parker, Michael H.; Brenneman, Douglas E.; Malatynska, Ewa; White, H. Steve; Klein, Brian D.; Wilcox, Karen S.; Milewski, Michael E.; Herb, Mark; Finley, Michael F. A.; Liu, Yi; Lubin, Mary Lou; Qin, Ning; Reitz, Allen B.; Maryanoff, Bruce E.

2014-01-01

Broad-spectrum anticonvulsants are of considerable interest as antiepileptic drugs, especially because of their potential for treating refractory patients. Such “neurostabilizers” have also been used to treat other neurological disorders, including migraine, bipolar disorder, and neuropathic pain. We synthesized a series of sulfamide derivatives (4–9, 10a–i, 11a, 11b, 12) and evaluated their anticonvulsant activity. Thus, we identified promising sulfamide 4 (JNJ-26489112) and explored its pharmacological properties. Compound 4 exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically-induced, and chemically-induced seizures. Mechanistically, 4 inhibited voltage-gated Na+ channels and N-type Ca2+ channels, and was effective as a K+ channel opener. The anticonvulsant profile of 4 suggests that it may be useful for treating multiple forms of epilepsy (generalized tonic-clonic, complex partial, absence seizures), including refractory (or pharmacoresistant) epilepsy, at dose levels that confer a good safety margin. On the basis of its pharmacology and other favorable characteristics, 4 was advanced into human clinical studies. PMID:24205976

Analysis of Organic Compounds in Mars Analog Samples

NASA Technical Reports Server (NTRS)

Mahaffy, P. R.; Brinckerhoff, W. B.; Buch, A.; Cabane, M.; Coll, P.; Demick, J.; Glavin, D. P.

2004-01-01

The detailed characterization of organic compounds that might be preserved in rocks, ices, or sedimentary layers on Mars would be a significant step toward resolving the question of the habitability and potential for life on that planet. The fact that the Viking gas chromatograph mass spectrometer (GCMS) did not detect organic compounds should not discourage further investigations since (a) an oxidizing environment in the near surface fines analyzed by Viking is likely to have destroyed many reduced carbon species; (b) there are classes of refractory or partially oxidized species such as carboxylic acids that would not have been detected by the Viking GCMS; and (c) the Viking landing sites are not representative of Mars overall. These factors motivate the development of advanced in situ analytical protocols to carry out a comprehensive survey of organic compounds in martian regolith, ices, and rocks. We combine pyrolysis GCMS for analysis of volatile species, chemical derivatization for transformation of less volatile organics, and laser desorption mass spectrometry (LDMS) for analysis of elements and more refractory, higher-mass organics. To evaluate this approach and enable a comparison with other measurement techniques we analyze organics in Mars simulant samples.

Temperature Dependent Electrical and Micromechanical Properties of Lanthanum Titanate with Additions of Yttria

NASA Technical Reports Server (NTRS)

Goldsby, Jon C.

2003-01-01

Lanthanum titanate (La2Ti2O7) a layered distorted perovskite (1) with space group Pna2(sub 1) has been shown to have potential as a high temperature piezoelectric (2). However this highly refractory oxide compound must be consolidated at relatively high temperatures approximately 1400 C. Commercial La2Ti207 powders were mechanically alloyed with additions of Y2O3 to lower the consolidation temperature by 300 C and to provide post processing mechanical stability. Temperature dependent electrical, elastic and anelastic behavior were selected as nondestructive means of evaluating the effects of yttria on the properties of this ferroceramic material.

40 CFR 62.1500 - Identification of Plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... mercury emission standards, and shutdown provisions for mass burn refractory MWC units. (3) Revision to... FR 63313, Dec. 6, 2001; 70 FR 9229, Feb. 25, 2005] Metals, Acid Gases, Organic Compounds and Nitrogen...

Preservation of nutritional-status in patients with refractory ascites due to hepatic cirrhosis who are undergoing repeated paracentesis.

PubMed

Sorrentino, Paolo; Castaldo, Giuseppe; Tarantino, Luciano; Bracigliano, Alessandra; Perrella, Alessandro; Perrella, Oreste; Fiorentino, Francesco; Vecchione, Raffaela; D' Angelo, Salvatore

2012-04-01

Refractory ascites in liver-cirrhosis is associated with a poor prognosis. We performed a prospective study to investigate whether aggressive nutritional-support could improve outcomes in cirrhotic patients. Cirrhotic patients undergoing serial large-volume paracentesis for refractory-ascites were enrolled and randomized into three groups. Group A received post-paracentesis intravenous nutritional-support in addition to a balanced oral diet and a late-evening protein snack, group B received the same oral nutritional-protocol as the first group but without parenteral support, and group C (the control group) received a low-sodium or sodium-free diet. Clinical, anthropometric and laboratory nutritional parameters and biochemical tests of liver and renal function were reported for 12 months of follow-up. We enrolled 120 patients, who were randomized into three groups of equal size. Patients on the nutritional-protocol showed better preservation of clinical, anthropometric and laboratory nutritional parameters that were associated with decreased deterioration of liver function compared with patients on the low-sodium or sodium-free diet (group C). Groups A and B had lower morbidity and mortality rates than the control group (C). Mortality rates were significantly better in patients who were treated with parenteral-nutritional-support than for the other two groups. In patients who were on the nutritional-protocol, there was a reduction in the requirement of taps for the treatment of refractory ascites. Post-paracentesis parenteral-nutritional-support with a balanced oral diet and an evening protein snack appears to be the best care protocol for patients with liver-cirrhosis that has been complicated by refractory-ascites. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Carotenoids are the likely precursor of a significant fraction of marine dissolved organic matter

PubMed Central

Arakawa, Neal; Aluwihare, Lihini I.; Simpson, Andre J.; Soong, Ronald; Stephens, Brandon M.; Lane-Coplen, Daniel

2017-01-01

The ocean’s biota sequester atmospheric carbon dioxide (CO2) in part by producing dissolved organic matter (DOM) that persists in the ocean for millennia. This long-term accumulation of carbon may be facilitated by abiotic and biotic production of chemical structures that resist degradation, consequently contributing disproportionately to refractory DOM. Compounds that are selectively preserved in seawater were identified in solid-phase extracted DOM (PPL-DOM) using comprehensive gas chromatography (GC) coupled to mass spectrometry (MS). These molecules contained cyclic head groups that were linked to isoprenoid tails, and their overall structures closely resembled carotenoid degradation products (CDP). The origin of these compounds in PPL-DOM was further confirmed with an in vitro β-carotene photooxidation experiment that generated water-soluble CDP with similar structural characteristics. The molecular-level identification linked at least 10% of PPL-DOM carbon, and thus 4% of total DOM carbon, to CDP. Nuclear magnetic resonance spectra of experimental CDP and environmental PPL-DOM overlapped considerably, which indicated that even a greater proportion of PPL-DOM was likely composed of CDP. The CDP-rich DOM fraction was depleted in radiocarbon (14C age > 1500 years), a finding that supports the possible long-term accumulation of CDP in seawater. By linking a specific class of widespread biochemicals to refractory DOM, this work provides a foundation for future studies that aim to examine how persistent DOM forms in the ocean. PMID:28959723

DEEP DESULFURIZATION OF DIESEL FUELS BY A NOVEL INTEGRATED APPROACH

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

Xiaoliang Ma; Uday Turaga; Shingo Watanabe

2004-05-01

The overall objective of this project is to explore a new desulfurization system concept, which consists of efficient separation of the refractory sulfur compounds from diesel fuel by selective adsorption, and effective hydrodesulfurization of the concentrated fraction of the refractory sulfur compounds in diesel fuels. Our approaches focused on (1) selecting and developing new adsorbents for selective adsorption of sulfur or sulfur compounds in commercial diesel fuel; (2) conducting the adsorption desulfurization of model fuels and real diesel fuels by the selective-adsorption-for-removing-sulfur (PSUSARS) process over various developed adsorbents, and examining the adsorptive desulfurization performance of various adsorbents; (3) developing andmore » evaluating the regeneration methods for various spent adsorbent; (4) developing new catalysts for hydrodesulfurization of the refractory sulfur existing in the commercial diesel fuel; (5) on the basis of the fundamental understanding of the adsorptive performance and regeneration natures of the adsorbents, further confirming and improving the conceptual design of the novel PSU-SARS process for deep desulfurization of diesel fuel Three types of adsorbents, the metal-chloride-based adsorbents, the activated nickel-based adsorbents and the metal-sulfide-based adsorbents, have been developed for selective adsorption desulfurization of liquid hydrocarbons. All of three types of the adsorbents exhibit the significant selectivity for sulfur compounds, including alkyl dibenzothiophenes (DBTs), in diesel fuel. Adsorption desulfurization of real diesel fuels (regular diesel fuel (DF), S: 325 ppmw; low sulfur diesel fuel (LSD-I), S: 47 ppmw) over the nickel-based adsorbents (A-2 and A-5) has been conducted at different conditions by using a flowing system. The adsorption capacity of DF over A-2 corresponding to an outlet sulfur level of 30 ppmw is 2.8 mg-S/g-A. The adsorption capacity of LSD-I over A-5 corresponding to the break-through point at 5.0 ppmw sulfur level is 0.35 mg-S/g-A. The spent A-5 can be regenerated by using H2 gas at a flowing rate of 40-50 ml/min, 500 C, and ambient pressure. Adsorption desulfurization of model diesel fuels over metal-sulfide-based adsorbents (A-6-1 and A-6-2) has been conducted at different temperatures to examine the capacity and selectivity of the adsorbents. A regeneration method for the spent metal-sulfide-based adsorbents has been developed. The spent A-6-1 can be easily regenerated by washing the spent adsorbent with a polar solvent followed by heating the adsorbent bed to remove the remainder solvent. Almost all adsorption capacity of the fresh A-6-1 can be recovered after the regeneration. On the other hand, a MCM-41-supported HDS catalyst was developed for deep desulfurization of the refractory sulfur compounds. The results show that the developed MCM-41-supported catalyst demonstrates consistently higher activity for the HDS of the refractory dibenzothiophenic sulfur compounds than the commercial catalyst. On the basis of the fundamental understanding of the adsorptive performance and regeneration natures of the adsorbents, the conceptual design of the novel PSU-SARS process for deep desulfurization of diesel fuel is confirmed and improved further.« less

Time-resolved analysis of particle emissions from residential biomass combustion - Emissions of refractory black carbon, PAHs and organic tracers

NASA Astrophysics Data System (ADS)

Nielsen, Ingeborg E.; Eriksson, Axel C.; Lindgren, Robert; Martinsson, Johan; Nyström, Robin; Nordin, Erik Z.; Sadiktsis, Ioannis; Boman, Christoffer; Nøjgaard, Jacob K.; Pagels, Joakim

2017-09-01

Time-resolved particle emissions from a conventional wood stove were investigated with aerosol mass spectrometry to provide links between combustion conditions, emission factors, mixing state of refractory black carbon and implications for organic tracer methods. The addition of a new batch of fuel results in low temperature pyrolysis as the fuel heats up, resulting in strong, short-lived, variable emission peaks of organic aerosol-containing markers of anhydrous sugars, such as levoglucosan (fragment at m/z 60). Flaming combustion results in emissions dominated by refractory black carbon co-emitted with minor fractions of organic aerosol and markers of anhydrous sugars. Full cycle emissions are an external mixture of larger organic aerosol-dominated and smaller thinly coated refractory black carbon particles. A very high burn rate results in increased full cycle mass emission factors of 66, 2.7, 2.8 and 1.3 for particulate polycyclic aromatic hydrocarbons, refractory black carbon, total organic aerosol and m/z 60, respectively, compared to nominal burn rate. Polycyclic aromatic hydrocarbons are primarily associated with refractory black carbon-containing particles. We hypothesize that at very high burn rates, the central parts of the combustion zone become air starved, leading to a locally reduced combustion temperature that reduces the conversion rates from polycyclic aromatic hydrocarbons to refractory black carbon. This facilitates a strong increase of polycyclic aromatic hydrocarbons emissions. At nominal burn rates, full cycle emissions based on m/z 60 correlate well with organic aerosol, refractory black carbon and particulate matter. However, at higher burn rates, m/z 60 does not correlate with increased emissions of polycyclic aromatic hydrocarbons, refractory black carbon and organic aerosol in the flaming phase. The new knowledge can be used to advance source apportionment studies, reduce emissions of genotoxic compounds and model the climate impacts of refractory black carbon, such as absorption enhancement by lensing.

Refractory inclusions with unusual chemical compositions from the Vigarano carbonaceous chondrite

NASA Technical Reports Server (NTRS)

Sylvester, Paul J.; Grossman, Lawrence; Macpherson, Glenn J.

1992-01-01

Neutron activation was used to test ten inclusions, nine Vigarano and one from Leoville, for major and trace elements. Six Vigarano refractory inclusions have refractory element fractionations that are rare or absent in Allende inclusions. Vig 1623-11 has Th/La and Ir/Mo ratios that are lower than those of any Allende Group I or modified Group I inclusions, and Os/La, Ir/La, and Zr/Hf ratios that are among the lowest in those inclusions. The low Os/La, Ir/La, and Ir/Mo ratios seem to require nonrepresentative sampling of condensate phase in the nebula to a degree that is usual for Allende Group I and modified group I inclusions. The nature and origins of the different inclusions are discussed.

Effects of Different Calcium Compounds on the Corrosion Resistance of Andalusite-Based Low-Cement Castables in Contact with Molten Al-Alloy

NASA Astrophysics Data System (ADS)

Adabifiroozjaei, Esmaeil; Saidi, Ali; Monshi, Ahmad; Koshy, Pramod

2011-04-01

Andalusite containing low-cement castables (LCCs) have been used in aluminum casthouses for several decades. CaF2 is commonly added to the refractory to improve its corrosion resistance mainly because of its role in the formation of anorthite (CaAl2Si2O8); the latter has been reported to decrease the penetration of molten aluminum alloys into refractories. This article investigates the effect of the addition of different calcium containing compounds (CaO, CaCO3, CaSO4, CaF2, Clinker white cement, calcia feldspar, wollastonite, and Ca3(PO4)2) on reactions with the refractory constituents to form anorthite as well as the effect of the additives on both the subsequent physical properties and the corrosion resistance of andalusite LCC refractories. Corrosion tests using the Alcoa cup test at temperatures (1123 K [850 °C] for 150 hours and 1433 K [1160 °C] for 72 hours) were conducted to determine the extent of penetration, whereas immersion tests in boiling water were conducted to determine the extent of open porosity in the material. Scanning electron microscopy coupled with energy dispersive spectrometer, optical microscopy, and X-ray diffraction techniques were employed to characterize the phase formations in the materials after the tests. The study demonstrated that both calcia feldspar and clinker white cement had the potential to be used as new additives for decreasing the penetration of molten Al-alloy into the refractory materials. Anorthite formation (in the refractory matrix), along with the absence of glassy phases, were responsible for the improvement in the corrosion resistance of the castables containing calcia feldspar. However, in the sample containing cement, the presence of calcium silicate phases were observed to resist reactions with molten aluminum. The observed results were validated using thermodynamic calculations, which indicated that tricalcium silicates (3CaO.SiO2) and dicalcium silicate (2CaO.SiO2) phases were more resistant than wollastonite (CaSiO3) for applications involving contact with molten aluminum.

Sources and atmospheric processing of size segregated aerosol particles revealed by stable carbon isotope ratios and chemical speciation.

PubMed

Masalaite, A; Holzinger, R; Ceburnis, D; Remeikis, V; Ulevičius, V; Röckmann, T; Dusek, U

2018-05-07

Size-segregated aerosol particles were collected during winter sampling campaigns at a coastal (55°37' N, 21°03'E) and an urban (54°64' N, 25°18' E) site. Organic compounds were thermally desorbed from the samples at different temperature steps ranging from 100 °C to 350 °C. The organic matter (OM) desorbed at each temperature step is analysed for stable carbon isotopes using an isotope ratio mass spectrometer (IRMS) and for individual organic compounds using a Proton Transfer Reaction Time-of-Flight Mass Spectrometer (PTR-MS). The OM desorbed at temperatures <200 °C was classified as less refractory carbon and the OM desorbed at temperatures between 200 °C and 350 °C was classified as more refractory carbon. At the coastal site, we identified two distinct time periods. The first period was more frequently influenced by marine air masses than the second time period, which was characterized by Easterly wind directions and continental air masses. During the first period OM contained a large fraction of hydrocarbons and had a carbon isotopic signature typical of liquid fossil fuels in the region. Organic mass spectra provide strong evidence that shipping emissions are a significant source of OM at this coastal site. The isotopic and chemical composition of OM during the second period at the coastal site was similar to the composition at the urban site. There was a clear distinction in source contribution between the less refractory OM and the more refractory OM at these sites. According to the source apportionment method used in this study, we were able to identify fossil fuel burning as predominant source of the less refractory OM in the smallest particles (D 50  < 0.18 μm), and biomass burning as predominant source of the more refractory OM in the larger size range (0.32 < D 50  < 1 μm). Copyright © 2018 Elsevier Ltd. All rights reserved.

Anti-TNF therapy for juvenile idiopathic arthritis-related uveitis

PubMed Central

Semeraro, Francesco; Arcidiacono, Barbara; Nascimbeni, Giuseppe; Angi, Martina; Parolini, Barbara; Costagliola, Ciro

2014-01-01

Juvenile idiopathic arthritis-related uveitis is the most common type of uveitis in childhood and one of the main causes of visual impairment in children. The introduction of biological treatment has widened the range of therapeutic options for children with uveitis refractory to standard nonbiologic immunosuppressants. Data from clinical trials suggest that both adalimumab and infliximab have demonstrated effectiveness and safety in open-label studies, although no large, randomized, controlled trials have been reported so far. The role of etanercept in treating juvenile idiopathic arthritis-related uveitis is not yet well defined. In our experience, anti-tumor necrosis factor therapy has been shown to be more effective than steroids and/or methotrexate in treating uveitis. Up to now, tumor necrosis factor blocking compounds have been reserved for the treatment of the most severe cases of refractory uveitis, and larger prospective clinical trials are required in order to better assess the safety of these new compounds. PMID:24711694

Anti-TNF therapy for juvenile idiopathic arthritis-related uveitis.

PubMed

Semeraro, Francesco; Arcidiacono, Barbara; Nascimbeni, Giuseppe; Angi, Martina; Parolini, Barbara; Costagliola, Ciro

2014-01-01

Juvenile idiopathic arthritis-related uveitis is the most common type of uveitis in childhood and one of the main causes of visual impairment in children. The introduction of biological treatment has widened the range of therapeutic options for children with uveitis refractory to standard nonbiologic immunosuppressants. Data from clinical trials suggest that both adalimumab and infliximab have demonstrated effectiveness and safety in open-label studies, although no large, randomized, controlled trials have been reported so far. The role of etanercept in treating juvenile idiopathic arthritis-related uveitis is not yet well defined. In our experience, anti-tumor necrosis factor therapy has been shown to be more effective than steroids and/or methotrexate in treating uveitis. Up to now, tumor necrosis factor blocking compounds have been reserved for the treatment of the most severe cases of refractory uveitis, and larger prospective clinical trials are required in order to better assess the safety of these new compounds.

Uranium carbide fission target R&D for RIA - an update

NASA Astrophysics Data System (ADS)

Greene, J. P.; Levand, A.; Nolen, J.; Burtseva, T.

2004-12-01

For the Rare Isotope Accelerator (RIA) facility, ISOL targets employing refractory compounds of uranium are being developed to produce radioactive ions for post-acceleration. The availability of refractory uranium compounds in forms that have good thermal conductivity, relatively high density, and adequate release properties for short-lived isotopes remains an important issue. Investigations using commercially obtained uranium carbide material and prepared into targets involving various binder materials have been carried out at ANL. Thin sample pellets have been produced for measurements of thermal conductivity using a new method based on electron bombardment with the thermal radiation observed using a two-color optical pyrometer and performed on samples as a function of grain size, pressing pressure and sintering temperature. Manufacture of uranium carbide powder has now been achieved at ANL. Simulations have been carried out on the thermal behavior of the secondary target assembly incorporating various heat shield configurations.

Electrochemical Synthesis of Binary and Ternary Refractory Compounds in the System Ti-Si-B from Chloride-Fluoride Melts

NASA Astrophysics Data System (ADS)

Devyatkin, Sergei V.

2007-09-01

Electrochemical synthesis of binary and ternary compounds in the system Ti-Si-B from chloridefluoride melts has been investigated by voltammetry and electrolysis. Electrochemical syntheses of titanium diboride, four titanium silicides (TiSi2, TiSi, Ti5Si4, Ti5Si3), silicon tetraboride and a new ternary compound, Ti5Si3B3, have been found to be one-step processes. The stoichiometry of the deposited compounds has been found to correlate with the bulk concentration of Ti, Si and B ions in the melt.

Long-term outcome of 31 cases of refractory acute promyelocytic leukemia treated with compound realgar natural indigo tablets administered alternately with chemotherapy

PubMed Central

LIU, YANFENG; HE, PENGCHENG; CHENG, XIAOYAN; ZHANG, MEI

2015-01-01

The aim of the present study was to investigate the long-term survival of patients with refractory acute promyelocytic leukemia (APL) that were administered alternately with compound realgar natural indigo tablet (CRNIT) treatment and chemotherapy. In total, 31 patients with refractory APL were administered with CRNIT treatment alternately with chemotherapy. The complete remission (CR) and relapse rates were estimated by bone marrow (BM) examination. The expression of the promyelocytic leukemia-retinoic acid receptor α (PML-RARα) fusion protein and the apoptosis rate in the retinoic acid (RA)-resistant NB4-R1 cell line administered with CRNIT treatment in vitro were measured by western blot analysis and flow cytometry, respectively. The patients were followed up for 12–60 months, with a median follow-up time of 43 months. The total continuous CR rate was 90.32% (28/31), and the duration of response was between 10.3 and 60 months (median, 42.4 months). The total relapse rate was 9.68% (3/31), and the median time of relapse was 13 months (range, 8–27 months). During the treatment with CRNITs, there was no evident BM depression and only limited side-effects were experienced. Additionally, in vitro cell molecular biology results revealed that CRNIT treatment resulted in a marked induction of apoptosis and degradation of the PML-RARα fusion protein. The present results revealed that CRNIT treatment in combination with chemotherapy is an effective and feasible therapy for the treatment of patients with refractory APL. PMID:26622649

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.

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

Refractory Research Group - U.S. DOE, Albany Research Center [Institution Profile

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

Bennett, James P.

2004-09-01

The refractory research group at the Albany Research Center (ARC) has a long history of conducting materials research within the U.S. Bureau of Mines, and more recently, within the U.S. Dept. of Energy. When under the U.S. Bureau of Mines, research was driven by national needs to develop substitute materials and to conserve raw materials. This mission was accomplished by improving refractory material properties and/or by recycling refractories using critical and strategic materials. Currently, as a U.S. Dept of Energy Fossil Energy field site, research is driven primarily by the need to assist DOE in meeting its vision to developmore » economically and environmentally viable technologies for the production of electricity from fossil fuels. Research at ARC impacts this vision by: • Providing information on the performance characteristics of materials being specified for the current generation of power systems; • Developing cost-effective, high performance materials for inclusion in the next generation of fossil power systems; and • Solving environmental emission and waste problems related to fossil energy systems. A brief history of past refractory research within the U.S. Bureau of Mines, the current refractory research at ARC, and the equipment and capabilities used to conduct refractory research at ARC will be discussed.« less

Method of coating graphite tubes with refractory metal carbides

DOEpatents

Wohlberg, C.

1973-12-11

A method of coating graphite tubes with a refractory metal carbide is described. An alkali halide is reacted with a metallic oxide, the metallic portion being selected from the IVth or Vth group of the Periodic Table, the resulting salt reacting in turn with the carbon to give the desired refractory metal carbide coating. (Official Gazette)

The effect of captopril and losartan on the electrophysiology of myocardial cells of myocardial ischemia rats.

PubMed

Shi, Xiangmin; Shan, Zhaoling; Yuan, Hongtao; Guo, Hongyang; Wang, Yutang

2014-01-01

This study aims to investigate the effect of captopril and losartan on the electrophysiology of myocardial cells parameters in ventricular vulnerable period and effective refractory period of myocardial ischemia rats. 96 wistar rats were enrolled in the study and divided into six groups: Captopril myocardial ischemia group, losartan myocardial ischemia group, myocardial ischemia control group, captopril normal group, losartan normal group and normal control group (n=16). We observed morphological changes of myocardial tissue in each group. The cardiac electrophysiological parameters in effective refractory period of each group were measured. Creatine kinase (CK), alanine aminotransferase (GOT), lactate dehydrogenase (LDH), the expression of Cardiotrophin 1 (CT-1) and malonaldehyde (MDA) were detected. Compared the losartan and captopril group with the control group, (P<0.05). Losartan and captopril can shorten the ventricular vulnerable period of the normal group and ischemic group. There was no interaction effect between losartan and captopril group and the acute myocardial ischemia group. The effect of losartan and captopril on time window in ventricular vulnerable period showed that compared with the control group (P<0.05). Losartan and captopril had a significant effect on prolonged effective refractory period of normal and ischemic rats. There was no interaction effect between losartan and captopril group and the acute myocardial ischemia group. Compared with the myocardial ischemia control group, CK, GOT, LDH and MDA decreased in captopril and losartan myocardial ischemia groups (P<0.05). Losartan and captopril had a significant effect on prolonged effective refractory period and shorten ventricular vulnerable period, they can also effectively prevent arrhythmias.

Refractory electrodes for joule heating and methods of using same

DOEpatents

Lamar, David A.; Chapman, Chris C.; Elliott, Michael L.

1998-01-01

A certain group of electrically conductive refractory materials presently known for use in high temperature applications as throat constructions, melter sidewalls, forehearth, stacks, port sills, hot face lining for slagging coal gasifiers, slag runners, and linings for nuclear waste encapsulation furnaces may be used as electrodes permitting joule heating at temperatures in excess of 1200 C. in excess of about 4400 hours even in the presence of transition group element(s). More specifically, the invention is an electrode for melting earthen materials, wherein the electrode is made from an electrically conductive refractory material, specifically at least one metal oxide wherein the metal is selected from the group consisting of chrome, ruthenium, rhodium, tin and combinations thereof.

High temperature solar selective coatings

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

Kennedy, Cheryl E

Improved solar collectors (40) comprising glass tubing (42) attached to bellows (44) by airtight seals (56) enclose solar absorber tubes (50) inside an annular evacuated space (54. The exterior surfaces of the solar absorber tubes (50) are coated with improved solar selective coatings {48} which provide higher absorbance, lower emittance and resistance to atmospheric oxidation at elevated temperatures. The coatings are multilayered structures comprising solar absorbent layers (26) applied to the meta surface of the absorber tubes (50), typically stainless steel, topped with antireflective Savers (28) comprising at least two layers 30, 32) of refractory metal or metalloid oxides (suchmore » as titania and silica) with substantially differing indices of refraction in adjacent layers. Optionally, at least one layer of a noble metal such as platinum can be included between some of the layers. The absorbent layers cars include cermet materials comprising particles of metal compounds is a matrix, which can contain oxides of refractory metals or metalloids such as silicon. Reflective layers within the coating layers can comprise refractory metal silicides and related compounds characterized by the formulas TiSi. Ti.sub.3SiC.sub.2, TiAlSi, TiAN and similar compounds for Zr and Hf. The titania can be characterized by the formulas TiO.sub.2, Ti.sub.3O.sub.5. TiOx or TiO.sub.xN.sub.1-x with x 0 to 1. The silica can be at least one of SiO.sub.2, SiO.sub.2x or SiO.sub.2xN.sub.1-x with x=0 to 1.« less

Rotor termination is critically dependent on kinetic properties of I kur inhibitors in an in silico model of chronic atrial fibrillation.

PubMed

Scholz, Eberhard P; Carrillo-Bustamante, Paola; Fischer, Fathima; Wilhelms, Mathias; Zitron, Edgar; Dössel, Olaf; Katus, Hugo A; Seemann, Gunnar

2013-01-01

Inhibition of the atrial ultra-rapid delayed rectifier potassium current (I Kur) represents a promising therapeutic strategy in the therapy of atrial fibrillation. However, experimental and clinical data on the antiarrhythmic efficacy remain controversial. We tested the hypothesis that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of channel blockade. A mathematical description of I Kur blockade was introduced into Courtemanche-Ramirez-Nattel models of normal and remodeled atrial electrophysiology. Effects of five model compounds with different kinetic properties were analyzed. Although a reduction of dominant frequencies could be observed in two dimensional tissue simulations for all compounds, a reduction of spiral wave activity could be only be detected in two cases. We found that an increase of the percent area of refractory tissue due to a prolongation of the wavelength seems to be particularly important. By automatic tracking of spiral tip movement we find that increased refractoriness resulted in rotor extinction caused by an increased spiral-tip meandering. We show that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of blockade. We find that an increase of the percent area of refractory tissue is the underlying mechanism for an increased spiral-tip meandering, resulting in the extinction of re-entrant circuits.

Rotor Termination Is Critically Dependent on Kinetic Properties of I Kur Inhibitors in an In Silico Model of Chronic Atrial Fibrillation

PubMed Central

Scholz, Eberhard P.; Carrillo-Bustamante, Paola; Fischer, Fathima; Wilhelms, Mathias; Zitron, Edgar; Dössel, Olaf; Katus, Hugo A.; Seemann, Gunnar

2013-01-01

Inhibition of the atrial ultra-rapid delayed rectifier potassium current (I Kur) represents a promising therapeutic strategy in the therapy of atrial fibrillation. However, experimental and clinical data on the antiarrhythmic efficacy remain controversial. We tested the hypothesis that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of channel blockade. A mathematical description of I Kur blockade was introduced into Courtemanche-Ramirez-Nattel models of normal and remodeled atrial electrophysiology. Effects of five model compounds with different kinetic properties were analyzed. Although a reduction of dominant frequencies could be observed in two dimensional tissue simulations for all compounds, a reduction of spiral wave activity could be only be detected in two cases. We found that an increase of the percent area of refractory tissue due to a prolongation of the wavelength seems to be particularly important. By automatic tracking of spiral tip movement we find that increased refractoriness resulted in rotor extinction caused by an increased spiral-tip meandering. We show that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of blockade. We find that an increase of the percent area of refractory tissue is the underlying mechanism for an increased spiral-tip meandering, resulting in the extinction of re-entrant circuits. PMID:24376659

[Impact of topical application of autologous platelet-rich gel on medical expenditure and length of stay in hospitals in diabetic patients with refractory cutaneous ulcers].

PubMed

Li, Lan; Wang, Chun; Wang, Yan; He, Li-Ping; Yang, Yan-Zhi; Chen, Li-Hong; Chen, Da-Wei; Li, Xiu-Jun; Ran, Xing-Wu

2012-09-01

To evaluate the potential financial benefit of topical application of autologous platelet-rich gel (APG) in treating diabetic refractory cutaneous ulcers. A single-center prospective randomized controlled trial was undertaken, with 117 patients with proven diabetic refractory cutaneous ulcers participating in the study. The patients who gave informed consents were randomly assigned into standard care group (n = 58) or standard care plus topical application of APG treatment group (n = 59). The outcome of healing and the medical expenditur and length of stay in the patients were compared between the two groups. The APG-treated group had better healing outcomes than the standard-treated group. The APG-treated group had 84.750 (50/59) complete healing and 98.31% improvement, higher than the 68.97% (40/58) and 75.86%, respectively, in the standard-treated group (P = 0.026). The median length for healing in the APG-treated patients was 36 days, shorter than the 45 days in the standard-treated patients (P = 0.012). The total medical expenditure and length of stay in hospitals were not significantly different between APG-treated patients [yen 38223 (23070-57398); 57 (41-94) days] and standard-treated patients [yen 35070 (24436-53649); 58 (31.75-58.50) days) (P = 0.455 and 0.301 respectively). Spendings on items such as medicine, artificial treatment, materials, interventional operation, surgical procedures, laboratory tests and other auxiliary examination, accommodations, meals, nursing care and debridement and dressing change were similar between the two groups (P > 0.05). There is an advantage for the topical application of APG on diabetic refractory cutaneous ulcers in terms of the healing outcomes. APG is a cost-effective choice for patients with diabetic refractory cutaneous ulcers.

PREPARATION OF PuF$sub 3$

DOEpatents

Benz, R.

1964-03-01

A process for preparing pure plutonium trifluoride is described in which a refractory plutonium compound is contacted with ammonium fluoride in a closed container at a pressure of at least 10 atmospheres and a temperature of about 550 deg C. (AEC)

Physical and Chemical Properties of Anthropogenic Aerosols: An Overview

EPA Science Inventory

Aerosol chemical composition is complex. Combustion aerosols can comprise tens of thousands of organic compounds, refractory brown and black carbon, heavy metals, cations, anions, salts, and other inorganic phases. Aerosol organic matter normally contains semivolatile material th...

Potential of bisbenzimidazole-analogs toward metronidazole-resistant Trichomonas vaginalis isolates.

PubMed

Korosh, Travis; Bujans, Emmanuel; Morada, Mary; Karaalioglu, Canan; Vanden Eynde, Jean Jacques; Mayence, Annie; Huang, Tien L; Yarlett, Nigel

2017-10-01

A bisoxyphenylene-bisbenzimidazole series with increasing aliphatic chain length (CH 2 to C 10 H 20 ) containing a meta- (m) or para (p)-benzimidazole linkage to the phenylene ring was tested for ability to inhibit the growth of metronidazole-susceptible (C1) and metronidazole-refractory (085) Trichomonas vaginalis isolates under aerobic and anaerobic conditions. Compound 3m, 2,2'-[α,ω-propanediylbis(oxy-1,3-phenylene)]bis-1H-benzimidazole, displayed a 5.5-fold lower minimum inhibitory concentration (MIC) toward T. vaginalis isolate 085 than metronidazole under aerobic growth conditions, (26 μm compared to 145 μm). A dose of 25 mg/kg per day for four days of compound 3m cured a subcutaneous mouse model infection using T. vaginalis isolates 286 (metronidazole susceptible) and 085 (metronidazole refractory). Compound 3m was weakly reduced by pyruvate:ferredoxin oxidoreductase, but unlike metronidazole was not dependent upon added ferredoxin. It is concluded from structure-activity relationships that there was no obvious trend based on the length of the central aliphatic chain, or the steric position of the bisbenzimidazole enabling prediction of biological activity. The compounds generally fulfill Lipinski's rile of five, indicating their potential as drug leads. © 2017 John Wiley & Sons A/S.

[Effect of furazolidone quadruple regimen plus dental plaque removal procedures as rescue treatment of refractory Helicobacter pylori infection].

PubMed

Gao, Wen; Hu, Fu-lian; Wang, Xiao-min

2011-03-29

To observe the effect of furazolidone quadruple regimen plus dental plaque removal procedures as rescue treatment of refractory H. pylori infection. A total of 104 patients with H. pylori positive [(13)C-urea breath test (UBT) or rapid urease test positive] failing in previous treatment two or more were enrolled and divided into 2 groups. One group (n = 64) were given quadruple regimen [proton pump inhibitor (PPI) + bismuth + amoxicillin + furazolidone, 10 days] treatment and dental plaque removal treatment. And the others (n = 40) received only quadruple regimen treatment. The status of H. pylori was detected by (13)C-UBT at 4 weeks post-therapy and the eradication rates of two groups were compared. The eradication rate of quadruple regimen + dental treatment group was 85.9% (55/64) while that of the other group 72.5% (29/40) (P = 0.091). The PPI + bismuth quadruple regimen plus dental plaque removal procedures as rescue treatment may boost the eradication rate of refractory H. pylori infection patients. And the furazolidone quadruple therapy can be chosen for the treatment of refractory H. pylori infection. Oral H. pylori infection may play a role in the failure of H. pylori infection treatment.

Method for producing uranium atomic beam source

DOEpatents

Krikorian, Oscar H.

1976-06-15

A method for producing a beam of neutral uranium atoms is obtained by vaporizing uranium from a compound UM.sub.x heated to produce U vapor from an M boat or from some other suitable refractory container such as a tungsten boat, where M is a metal whose vapor pressure is negligible compared to that of uranium at the vaporization temperature. The compound, for example, may be the uranium-rhenium compound, URe.sub.2. An evaporation rate in excess of about 10 times that of conventional uranium beam sources is produced.

Chemical plating method of preparing radiation source material

DOEpatents

Smith, P.K.; Huntoon, R.T.; Mosley, W.C. Jr.

1973-12-11

A uniform dispersion of a radioisotope within a noble metal matrix is provided by chemically plating a noble metal coating onto particles including a dissociable compound of the mdioisotope. A suspension of the dissociable compound in a chemically reductive solution is prepared and noble metal cations added to produce the noble metal coatings. The coated particles are filtered, dried and heated to calcine the dissociable compound to a refractory powder. The powder can be encapsulated in measured portions or consolidated and shaped into an elongated form for easy apportionnnent as radiation source material. (Official Gazette)

Risk factors for esophageal stenosis after entire circumferential endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

PubMed

Miwata, Tomohiro; Oka, Shiro; Tanaka, Shinji; Kagemoto, Kenichi; Sanomura, Yoji; Urabe, Yuji; Hiyama, Toru; Chayama, Kazuaki

2016-09-01

Endoscopic submucosal dissection (ESD) is used to perform en block resection for esophageal squamous cell carcinoma, but it is strongly associated with postoperative stenosis, especially during entire circumferential resection. This study aimed to clarify the risk factors for refractory postoperative stenosis after entire circumferential esophageal ESD. Nineteen patients who underwent entire circumferential esophageal ESD from February 2006 to December 2013 at Hiroshima University Hospital were divided into two groups: refractory postoperative stenosis [≥6 endoscopic balloon dilation (EBD) procedures, 12 lesions in 12 patients] and non-refractory postoperative stenosis (≤5 EBD procedures, 7 lesions in 7 patients). We retrospectively examined the patient factors (age, sex, alcohol consumption, smoking index, and chemoradiation therapy history), tumor factors (location, macroscopic type, fibrosis, and depth), and treatment factors (mean procedure time, entire circumferential resection diameter, muscle layer damage, and steroid administration method) between the two groups. Muscle layer damage (p = 0.019) and ≥5 cm of longitudinal mucosal defect length after entire circumferential esophageal ESD (p = 0.010) were significant factors associated with the refractory group. Regarding the patient and tumor factors, there were no significant differences between the two groups. Our data suggest that refractory post-ESD stenosis occurs after entire circumferential esophageal ESD with muscle layer damage and ≥5 cm of longitudinal mucosal defect length.

Improved refractory performance through partnership

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

Linck, F.E.; Peters, D.

1995-12-31

From the early designs and construction of Circulating Fluidized Bed (CFB) boilers, many improvements have been made based upon observations of performance. Included in these improvements have been the refractory linings. The early refractory linings were subjected to extreme fluctuations in temperatures as the units experienced up and down conditions. As the designs were improved refractory failures were mostly due to the operating conditions and other mechanical stresses rather than continual shutdowns and startups. More recent problems observed with refractory linings are localized areas of high erosion, corrosion and cracking which result in hot spots and eventual shutdowns for repair.more » Today the objective of refractory suppliers and installers is to strive towards planned shutdowns rather than emergency shutdowns. This can be accomplished through partnerships between operations, material suppliers and installers. In essence, the concept is a cooperative effort between these groups to solve the variety of refractory problems in order to achieve longer refractory lining performance and less chance for emergency shutdowns. The reliability of the refractory lining is dependent on the successful combination of the material selected, proper design and the installation of the refractory material. Where these three elements combine, the lining has the best chance of performing its intended purpose.« less

Production method for making rare earth compounds

DOEpatents

McCallum, R.W.; Ellis, T.W.; Dennis, K.W.; Hofer, R.J.; Branagan, D.J.

1997-11-25

A method of making a rare earth compound, such as a earth-transition metal permanent magnet compound, without the need for producing rare earth metal as a process step, comprises carbothermically reacting a rare earth oxide to form a rare earth carbide and heating the rare earth carbide, a compound-forming reactant (e.g., a transition metal and optional boron), and a carbide-forming element (e.g., a refractory metal) that forms a carbide that is more thermodynamically favorable than the rare earth carbide whereby the rare earth compound (e.g., Nd{sub 2}Fe{sub 14}B or LaNi{sub 5}) and a carbide of the carbide-forming element are formed.

Production method for making rare earth compounds

DOEpatents

McCallum, R. William; Ellis, Timothy W.; Dennis, Kevin W.; Hofer, Robert J.; Branagan, Daniel J.

1997-11-25

A method of making a rare earth compound, such as a earth-transition metal permanent magnet compound, without the need for producing rare earth metal as a process step, comprises carbothermically reacting a rare earth oxide to form a rare earth carbide and heating the rare earth carbide, a compound-forming reactant (e.g. a transition metal and optional boron), and a carbide-forming element (e.g. a refractory metal) that forms a carbide that is more thermodynamically favorable than the rare earth carbide whereby the rare earth compound (e.g. Nd.sub.2 Fe.sub.14 B or LaNi.sub.5) and a carbide of the carbide-forming element are formed.

Refractory Hypertension: Determination of Prevalence, Risk Factors and Comorbidities in a Large, Population-Based Cohort

PubMed Central

Calhoun, David A.; Booth, John N.; Oparil, Suzanne; Irvin, Marguerite R.; Shimbo, Daichi; Lackland, Daniel T.; Howard, George; Safford, Monika M.; Muntner, Paul

2014-01-01

Refractory hypertension is an extreme phenotype of antihypertensive treatment failure. Participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a large (n=30,239), population-based cohort were evaluated to determine the prevalence of refractory hypertension and associated cardiovascular risk factors and comorbidities. Refractory hypertension was defined as uncontrolled blood pressure (systolic/diastolic ≥ 140/90 mm Hg) on ≥ 5 antihypertensive drug classes. Participants with resistant hypertension (systolic/diastolic ≥140/90 mm Hg on ≥ 3 or<140/90 mm Hg on ≥ 4 antihypertensive classes) and all treated hypertensive participants served as comparator groups. Of 14,809 REGARDS participants receiving antihypertensive treatment, 78 (0.5%) had refractory hypertension. The prevalence of refractory hypertension was 3.6% among participants with resistant hypertension(n=2,144) and 41.7% among participants on 5 or more antihypertensive drug classes. Among all hypertensive participants, African American race, male gender, living in the stroke belt or buckle, higher body mass index, lower heart rate, reduced estimated glomerular filtration rate, albuminuria, diabetes and history of stroke and coronary heart disease were associated with refractory hypertension. Compared to resistant hypertension, prevalence ratios for refractory hypertension were increased for African Americans (3.00, 95% CI 1.68 – 5.37) and those with albuminuria (2.22, 95% CI 1.40 – 3.52) and diabetes (2.09, 95% CI 1.32 – 3.31). The median 10-year Framingham risk for coronary heart disease and stroke was higher among participants with refractory hypertension compared to either comparator group. These data indicate that while resistant hypertension is relatively common among treated hypertensive patients, true antihypertensive treatment failure is rare. PMID:24324035

Refractory electrodes for joule heating and methods of using same

DOEpatents

Lamar, D.A.; Chapman, C.C.; Elliott, M.L.

1998-05-12

A certain group of electrically conductive refractory materials presently known for use in high temperature applications as throat constructions, melter sidewalls, forehearth, stacks, port sills, hot face lining for slagging coal gasifiers, slag runners, and linings for nuclear waste encapsulation furnaces may be used as electrodes permitting joule heating at temperatures in excess of 1,200 C in excess of about 4400 hours even in the presence of transition group element(s). More specifically, the invention is an electrode for melting earthen materials, wherein the electrode is made from an electrically conductive refractory material, specifically at least one metal oxide wherein the metal is selected from the group consisting of chrome, ruthenium, rhodium, tin and combinations thereof. 2 figs.

Ketamine, as adjuvant analgesics for patients with refractory cancer pain, does affect IL-2/IFN-γ expression of T cells in vitro?: A prospective, randomized, double-blind study.

PubMed

Zhou, Naibao; Fu, Zhijian; Li, Hao; Wang, Kaiguo

2017-04-01

Ketamine has been used as an analgesic adjuvant with morphine in the treatment of refractory cancer pain recently. But both morphine and ketamine have been reported to produce a number of immunomodulatory effects. The current study was performed to assess whether the concentration of ketamine, as adjuvant analgesics for patient with refractory cancer pain, was related to its effect on T cells interleukin-2 (IL-2)/interferon-γ (IFN-γ) expression in vitro. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood of patients with refractory cancer pain over a Ficoll-Hypaque density gradient. T cells were isolated from by positive selection using anti-CD3 beads. T cells were then treated with vehicle (C group), morphine (200 ng/mL, M group), morphine (200 ng/mL), and different dose of ketamine (100, 200, 1000 ng/mL; MK1, MK5, MK10 group) for 24 hours before stimulation with anti-CD3 and anti-CD28. Then supernatant IL-2 and IFN-γ protein analysis, quantitative reverse transcription polymerase chain reaction (RT-PCR) for IL-2 and IFN-γ were done. There were no significant difference of supernatant IL-2 and IFN-γ among C group, M group, and MK1 group, but the mRNA of M group and MK1 group were decreased compared with C group (P < .05). Compared with C group, both of the supernatant protein and the mRNA of MK5 group and MK10 group were all significantly decreased (P < .01). Compared with M group, both of the supernatant protein and the mRNA of MK5 group and MK10 group were all decreased (P < .05), while supernatant IL-2 and the mRNA of MK10 group were significantly decreased (P < .01). In conclusion, we confirmed that just as morphine, ketamine dose-dependently suppressed IL-2 and IFN-γ of activated T lymphocyte of patients with refractory cancer pain in vitro, but the inhibitory action of low dose ketamine could be neglected.

Ketamine, as adjuvant analgesics for patients with refractory cancer pain, does affect IL-2/IFN-γ expression of T cells in vitro?

PubMed Central

Zhou, Naibao; Fu, Zhijian; Li, Hao; Wang, Kaiguo

2017-01-01

Abstract Background: Ketamine has been used as an analgesic adjuvant with morphine in the treatment of refractory cancer pain recently. But both morphine and ketamine have been reported to produce a number of immunomodulatory effects. The current study was performed to assess whether the concentration of ketamine, as adjuvant analgesics for patient with refractory cancer pain, was related to its effect on T cells interleukin-2 (IL-2)/interferon-γ (IFN-γ) expression in vitro. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood of patients with refractory cancer pain over a Ficoll-Hypaque density gradient. T cells were isolated from by positive selection using anti-CD3 beads. T cells were then treated with vehicle (C group), morphine (200 ng/mL, M group), morphine (200 ng/mL), and different dose of ketamine (100, 200, 1000 ng/mL; MK1, MK5, MK10 group) for 24 hours before stimulation with anti-CD3 and anti-CD28. Then supernatant IL-2 and IFN-γ protein analysis, quantitative reverse transcription polymerase chain reaction (RT-PCR) for IL-2 and IFN-γ were done. Results: There were no significant difference of supernatant IL-2 and IFN-γ among C group, M group, and MK1 group, but the mRNA of M group and MK1 group were decreased compared with C group (P < .05). Compared with C group, both of the supernatant protein and the mRNA of MK5 group and MK10 group were all significantly decreased (P < .01). Compared with M group, both of the supernatant protein and the mRNA of MK5 group and MK10 group were all decreased (P < .05), while supernatant IL-2 and the mRNA of MK10 group were significantly decreased (P < .01). Conclusion: In conclusion, we confirmed that just as morphine, ketamine dose-dependently suppressed IL-2 and IFN-γ of activated T lymphocyte of patients with refractory cancer pain in vitro, but the inhibitory action of low dose ketamine could be neglected. PMID:28422864

Antifungal Compounds against Candida Infections from Traditional Chinese Medicine

PubMed Central

2017-01-01

Infections caused by Candida albicans, often refractory and with high morbidity and mortality, cause a heavy burden on the public health while the current antifungal drugs are limited and are associated with toxicity and resistance. Many plant-derived molecules including compounds isolated from traditional Chinese medicine (TCM) are reported to have antifungal activity through different targets such as cell membrane, cell wall, mitochondria, and virulence factors. Here, we review the recent progress in the anti-Candida compounds from TCM, as well as their antifungal mechanisms. Considering the diverse targets and structures, compounds from TCM might be a potential library for antifungal drug development. PMID:29445739

SAR202 Genomes from the Dark Ocean Predict Pathways for the Oxidation of Recalcitrant Dissolved Organic Matter.

PubMed

Landry, Zachary; Swan, Brandon K; Herndl, Gerhard J; Stepanauskas, Ramunas; Giovannoni, Stephen J

2017-04-18

Deep-ocean regions beyond the reach of sunlight contain an estimated 615 Pg of dissolved organic matter (DOM), much of which persists for thousands of years. It is thought that bacteria oxidize DOM until it is too dilute or refractory to support microbial activity. We analyzed five single-amplified genomes (SAGs) from the abundant SAR202 clade of dark-ocean bacterioplankton and found they encode multiple families of paralogous enzymes involved in carbon catabolism, including several families of oxidative enzymes that we hypothesize participate in the degradation of cyclic alkanes. The five partial genomes encoded 152 flavin mononucleotide/F420-dependent monooxygenases (FMNOs), many of which are predicted to be type II Baeyer-Villiger monooxygenases (BVMOs) that catalyze oxygen insertion into semilabile alicyclic alkanes. The large number of oxidative enzymes, as well as other families of enzymes that appear to play complementary roles in catabolic pathways, suggests that SAR202 might catalyze final steps in the biological oxidation of relatively recalcitrant organic compounds to refractory compounds that persist. IMPORTANCE Carbon in the ocean is massively sequestered in a complex mixture of biologically refractory molecules that accumulate as the chemical end member of biological oxidation and diagenetic change. However, few details are known about the biochemical machinery of carbon sequestration in the deep ocean. Reconstruction of the metabolism of a deep-ocean microbial clade, SAR202, led to postulation of new biochemical pathways that may be the penultimate stages of DOM oxidation to refractory forms that persist. These pathways are tied to a proliferation of oxidative enzymes. This research illuminates dark-ocean biochemistry that is broadly consequential for reconstructing the global carbon cycle. Copyright © 2017 Landry et al.

Facilitation and refractoriness of the electrically evoked compound action potential.

PubMed

Hey, Matthias; Müller-Deile, Joachim; Hessel, Horst; Killian, Matthijs

2017-11-01

In this study we aim to resolve the contributions of facilitation and refractoriness at very short pulse intervals. Measurements of the refractory properties of the electrically evoked compound action potential (ECAP) of the auditory nerve in cochlear implant (CI) users at inter pulse intervals below 300 μs are influenced by facilitation and recovery effects. ECAPs were recorded using masker pulses with a wide range of current levels relative to the probe pulse levels, for three suprathreshold probe levels and pulse intervals from 13 to 200 μs. Evoked potentials were measured for 21 CI patients by using the masked response extraction artifact cancellation procedure. During analysis of the measurements the stimulation current was not used as absolute value, but in relation to the patient's individual ECAP threshold. This enabled a more general approach to describe facilitation as a probe level independent effect. Maximum facilitation was found for all tested inter pulse intervals at masker levels near patient's individual ECAP threshold, independent from probe level. For short inter pulse intervals an increased N 1 P 1 amplitude was measured for subthreshold masker levels down to 120 CL below patient's individual ECAP threshold in contrast to the recreated state. ECAPs recorded with inter pulse intervals up to 200 μs are influenced by facilitation and recovery. Facilitation effects are most pronounced for masker levels at or below ECAP threshold, while recovery effects increase with higher masker levels above ECAP threshold. The local maximum of the ECAP amplitude for masker levels around ECAP threshold can be explained by the mutual influence of maximum facilitation and minimal refractoriness. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Experimental evidence for an effect of early-diagenetic interaction between labile and refractory marine sedimentary organic matter on nitrogen dynamics

NASA Astrophysics Data System (ADS)

Turnewitsch, Robert; Domeyer, Bettina; Graf, Gerhard

2007-05-01

In most natural sedimentary systems labile and refractory organic material (OM) occur concomitantly. Little, however, is known on how different kinds of OM interact and how such interactions affect early diagenesis in sediments. In a simple sediment experiment, we investigated how interactions of OM substrates of different degradability affect benthic nitrogen (N) dynamics. Temporal evolution of a set of selected biogeochemical parameters was monitored in sandy sediment over 116 days in three experimental set-ups spiked with labile OM (tissue of Mytilus edulis), refractory OM (mostly aged Zostera marina and macroalgae), and a 1:1 mixture of labile and refractory OM. The initial amounts of particulate organic carbon (POC) were identical in the three set-ups. To check for non-linear interactions between labile and refractory OM, the evolution of the mixture system was compared with the evolution of the simple sum of the labile and refractory systems, divided by two. The sum system is the experimental control where labile and refractory OM are virtually combined but not allowed to interact. During the first 30 days there was evidence for net dissolved-inorganic-nitrogen (DIN) production followed by net DIN consumption. (Here 'DIN' is the sum of ammonium, nitrite and nitrate.) After ˜ 30 days a quasi steady state was reached. Non-linear interactions between the two types of OM were reflected by three main differences between the early-diagenetic evolutions of nitrogen dynamics of the mixture and sum (control) systems: (1) In the mixture system the phases of net DIN production and consumption commenced more rapidly and were more intense. (2) The mixture system was shifted towards a more oxidised state of DIN products [as indicated by increased (nitrite + nitrate)/(ammonium) ratios]. (3) There was some evidence that more OM, POC and particulate nitrogen were preserved in the mixture system. That is, in the mixture system more particulate OM was preserved while a higher proportion of the decomposed particulate N was converted into inorganic N. It can be concluded that during the first days and weeks of early diagenesis the magnitude and composition of the flux of decompositional dissolved N-compounds from sediments into the overlying water was influenced by non-linear interactions of OM substrates of different degradability. Given these experimental results it is likely that the relative spatial distributions of OM of differing degradability in sediments control the magnitude and composition of the return flux of dissolved N-bearing compounds from sediments into the overlying water column.

DEXAMETHASONE IMPLANT FOR DIABETIC MACULAR EDEMA IN NAIVE COMPARED WITH REFRACTORY EYES: The International Retina Group Real-Life 24-Month Multicenter Study. The IRGREL-DEX Study.

PubMed

Iglicki, Matias; Busch, Catharina; Zur, Dinah; Okada, Mali; Mariussi, Miriana; Chhablani, Jay Kumar; Cebeci, Zafer; Fraser-Bell, Samantha; Chaikitmongkol, Voraporn; Couturier, Aude; Giancipoli, Ermete; Lupidi, Marco; Rodríguez-Valdés, Patricio J; Rehak, Matus; Fung, Adrian Tien-Chin; Goldstein, Michaella; Loewenstein, Anat

2018-04-24

To investigate efficacy and safety of repeated dexamethasone (DEX) implants over 24 months, in diabetic macular edema (DME) eyes that were treatment naive compared with eyes refractory to anti-vascular endothelial growth factor treatment, in a real-life environment. This multicenter international retrospective study assessed best-corrected visual acuity and central subfield thickness (CST) of naive and refractory eyes to anti-vascular endothelial growth factor injections treated with dexamethasone implants. Safety data (intraocular pressure rise and cataract surgery) were recorded. A total of 130 eyes from 125 patients were included. Baseline best-corrected visual acuity and CST were similar for naive (n = 71) and refractory eyes (n = 59). Both groups improved significantly in vision after 24 months (P < 0.001). However, naive eyes gained statistically significantly more vision than refractory eyes (+11.3 ± 10.0 vs. 7.3 ± 2.7 letters, P = 0.01) and were more likely to gain ≥10 letters (OR 3.31, 95% CI 1.19-9.24, P = 0.02). At 6, 12, and 24 months, CST was significantly decreased compared with baseline in both naive and refractory eyes; however, CST was higher in refractory eyes than in naive eyes (CST 279 ± 61 vs. 313 ± 125 μm, P = 0.10). Over a follow-up of 24 months, vision improved in diabetic macular edema eyes after treatment with dexamethasone implants, both in eyes that were treatment naive and eyes refractory to anti-vascular endothelial growth factor treatment; however, improvement was greater in naive eyes.

USE OF GRANULAR GRAPHITE FOR ELECTROLYTIC DECHLORINATION OF TRICHLOROETHYLENE

EPA Science Inventory

Granular graphite is a potential electrode material for the electrochemical remediation of refractory chlorinated organic compounds such as trichloroethylene (TCE). However, the use of granular graphite can complicate the experimental results. On one hand, up to 99% of TCE was re...

Analysis of the chemical and physical properties of combustion aerosols: Properties overview

EPA Science Inventory

Aerosol chemical composition is remarkably complex. Combustion aerosols can comprise tens of thousands of organic compounds and fragments, refractory carbon, metals, cations, anions, salts, and other inorganic phases and substituents [Hays et al., 2004]. Aerosol organic matter no...

Novel Compound Heterozygous Mutations Expand the Recognized Phenotypes of FARS2-Linked Disease.

PubMed

Walker, Melissa A; Mohler, Kyle P; Hopkins, Kyle W; Oakley, Derek H; Sweetser, David A; Ibba, Michael; Frosch, Matthew P; Thibert, Ronald L

2016-08-01

Mutations in mitochondrial aminoacyl-tRNA synthetases are an increasingly recognized cause of human diseases, often arising in individuals with compound heterozygous mutations and presenting with system-specific phenotypes, frequently neurologic. FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase (mtPheRS), perturbations of which have been reported in 6 cases of an infantile, lethal disease with refractory epilepsy and progressive myoclonus. Here the authors report the case of juvenile onset refractory epilepsy and progressive myoclonus with compound heterozygous FARS2 mutations. The authors describe the clinical course over 6 years of care at their institution and diagnostic studies including electroencephalogram (EEG), brain magnetic resonance imaging (MRI), serum and cerebrospinal fluid analyses, skeletal muscle biopsy histology, and autopsy gross and histologic findings, which include features shared with Alpers-Huttenlocher syndrome, Leigh syndrome, and a previously published case of FARS2 mutation associated infantile onset disease. The authors also present structure-guided analysis of the relevant mutations based on published mitochondrial phenylalanyl transfer RNA synthetase and related protein crystal structures as well as biochemical analysis of the corresponding recombinant mutant proteins. © The Author(s) 2016.

A prospective comparative study on neovascular glaucoma and non-neovascular refractory glaucoma following Ahmed glaucoma valve implantation.

PubMed

Li, Zheng; Zhou, Minwen; Wang, Wei; Huang, Wenbin; Chen, Shida; Li, Xingyi; Gao, Xinbo; Zhang, Xiulan

2014-01-01

Neovascular glaucoma is a refractory disease, and difficult to manage. The aim of this study was to evaluate the clinical outcomes of Ahmed glaucoma valve implantation (AGVI) in neovascular glaucoma (NVG) and non-NVG patients. This prospective, non-randomized study included 55 eyes of 55 patients with refractory glaucoma; 27 had NVG (NVG group) and 28 had non-NVG (non-NVG group). All of the patients underwent AGVI. The NVG group was adjunctively injected with intravitreal ranibizumab/bevacizumab (IVR/IVB) before AGVI. Intraocular pressure (IOP) was the primary outcome measure in this study. Surgical success rate, number of antiglaucoma medications used, best corrected visual acuity (BCVA), and postoperative complications were analyzed between the groups. All of the patients completed the study (follow-up of 12 months). Kaplan-Meier survival curve analysis indicated that the qualified success rates in the NVG and non-NVG groups at 12 months were 70.5% and 92.9%, respectively; this difference was significant (P = 0.036). The complete success rates in the NVG and non-NVG groups at 12 months were 66.7% and 89.3%, respectively (P = 0.049). Compared with preoperative examinations, the postoperative mean IOP and use of medications were significantly lower at all follow-up time points in both groups (all P < 0.05). There were significant differences in BCVA between the two groups at the 12-month follow-up (χ(2) = 9.86, P = 0.020). Cox proportional hazards regression showed NVG as a risk factor for surgical failure (RR = 15.08, P = 0.033). Postoperative complications were similar between the two groups. AGVI is a safe and effective procedure in refractory glaucoma, but the success rate of surgery was related to the type of refractory glaucoma. The complete and qualified success rates of NVG patient adjunctive anti-vascular endothelial growth factor treatment are still lower than those of non-NVG patients.

Focus on Fotemustine.

PubMed

De Rossi, A; Rossi, L; Laudisi, A; Sini, V; Toppo, L; Marchesi, F; Tortorelli, G; Leti, M; Turriziani, M; Aquino, A; Bonmassar, E; De Vecchis, L; Torino, F

2006-12-01

Fotemustine is a cytotoxic alkylating agent, belonging to the group of nitrosourea family. Its mechanism of action is similar to that of other nitrosoureas, characterized by a mono-functional/bi-functional alkylating activity. Worth of consideration is the finding that the presence of high levels of the DNA repair enzyme O6-methylguanine-DNA-methyltransferase (MGMT) in cancer cells confers drug resistance. In different clinical trials Fotemustine showed a remarkable antitumor activity as single agent, and in association with other antineoplastic compounds or treatment modalities. Moreover, its toxicity is generally considered acceptable. The drug has been employed in the treatment of metastatic melanoma, and, on the basis of its pharmacokinetic properties, in brain tumors, either primitive or metastatic. Moreover, Fotemustine shows pharmacodynamic properties similar to those of mono-functional alkylating compounds (e.g. DNA methylating drugs, such as Temozolomide), that have been recently considered for the management of acute refractory leukaemia. Therefore, it is reasonable to assume that this agent could be a good candidate to play a potential role in haematological malignancies.

Symptom changes in five dimensions of the Positive and Negative Syndrome Scale in refractory psychosis.

PubMed

Woodward, Todd S; Jung, Kwanghee; Smith, Geoffrey N; Hwang, Heungsun; Barr, Alasdair M; Procyshyn, Ric M; Flynn, Sean W; van der Gaag, Mark; Honer, William G

2014-12-01

Refractory psychosis units currently have little information regarding which symptoms profiles should be expected to respond to treatment. In the current study, we provide this information using structural equation modeling of Positive and Negative Syndrome Scale (PANSS) ratings at admission and discharge on a sample of 610 patients admitted to a treatment refractory psychosis program at a Canadian tertiary care unit between 1990 and 2011. The hypothesized five-dimensional structure of the PANSS fit the data well at both admission and discharge, and the latent variable scores are reported as a function of symptom dimension and diagnostic category. The results suggest that, overall, positive symptoms (POS) responded to treatment better than all other symptoms dimensions, but for the schizoaffective and bipolar groups, greater response on POS was observed relative to the schizophrenia and major depression groups. The major depression group showed the most improvement on negative symptoms and emotional distress, and the bipolar group showed the most improvement on disorganization. Schizophrenia was distinct from schizoaffective disorder in showing reduced treatment response on all symptom dimensions. These results can assist refractory psychosis units by providing information on how PANSS symptom dimensions respond to treatment and how this depends on diagnostic category.

Alkali metal-refractory metal biphase electrode for AMTEC

NASA Technical Reports Server (NTRS)

Williams, Roger M. (Inventor); Bankston, Clyde P. (Inventor); Cole, Terry (Inventor); Khanna, Satish K. (Inventor); Jeffries-Nakamura, Barbara (Inventor); Wheeler, Bob L. (Inventor)

1989-01-01

An electrode having increased output with slower degradation is formed of a film applied to a beta-alumina solid electrolyte (BASE). The film comprises a refractory first metal M.sup.1 such as a platinum group metal, suitably platinum or rhodium, capable of forming a liquid or a strong surface adsorption phase with sodium at the operating temperature of an alkali metal thermoelectric converter (AMTEC) and a second refractory metal insoluble in sodium or the NaM.sup.1 liquid phase such as a Group IVB, VB or VIB metal, suitably tungsten, molybdenum, tantalum or niobium. The liquid phase or surface film provides fast transport through the electrode while the insoluble refractory metal provides a structural matrix for the electrode during operation. A trilayer structure that is stable and not subject to deadhesion comprises a first, thin layer of tungsten, an intermediate co-deposited layer of tungsten-platinum and a thin surface layer of platinum.

Effects of Different Barium Compounds on the Corrosion Resistance of Andalusite-Based Low-Cement Castables in Contact with Molten Al-Alloy

NASA Astrophysics Data System (ADS)

Adabifiroozjaei, Esmaeil; Koshy, Pramod; Rastkerdar, Ebad

2011-08-01

An experimental study was conducted to investigate the interfacial phenomena between an Al alloy and andalusite low-cement castables (LCCs) containing fixed contents of barium compounds (BaO, BaSO4, and BaCO3) at 1123 K and 1433 K (850 °C and 1160 °C) using the Alcoa cup test. Interfacial reaction products and phases formed during heat treatment of the refractory samples were characterized using scanning electron microscopy (SEM) coupled with energy dispersive spectrometry (EDS) and X-ray diffraction analysis (XRD). The addition of both BaO and BaSO4 led to a significant reduction of alloy penetration into the refractory. Hexa-celsian formation was observed in both these refractories, which drastically increased their corrosion resistance. Barite decomposition was observed at 1373 K (1100 °C) in the presence of alumina and silica, which was the precursor for hexa-celsian formation. Barium silicates were formed in all samples containing additives; however, this did not have any major influence on the corrosion resistance. Solidified eutectics of BaSi2 and α-BaAl2Si2 formed in all these samples, which acted as an interfacial barrier that prevented additional molten aluminum penetration; however, the positive effect of intermetallic formation was offset by glassy phase formation in samples containing BaCO3 as the additive.

Computer-aided design, synthesis and biological assay of p-methylsulfonamido phenylethylamine analogues.

PubMed

Liu, H; Ji, M; Jiang, H; Liu, L; Hua, W; Chen, K; Ji, R

2000-10-02

Class III antiarrhythmic agents selectively delay the effective refractory period (ERP) and increase the transmembrance action potential duration (APD). Based on our previous studies, a set of 17 methylsulfonamido phenylethylamine analogues were investigated by 3D-QSAR techniques of CoMFA and CoMSIA. The 3D-QSAR models proved a good predictive ability, and could describe the steric, electrostatic and hydrophobic requirements for recognition forces of the receptor site. According to the clues provided by this 3D-QSAR analysis, we designed and synthesized a series of new analogues of methanesulfonamido phenylethylamine (VIa-i). Pharmacological assay indicated that the effective concentrations of delaying the functional refractory period (FRP) 10ms of these new compounds have a good correlation with the 3D-QSAR predicted values. It is remarkable that the maximal percent change of delaying FRP in microM of compound VIc is much higher than that of dofetilide. The results showed that the 3D-QSAR models are reliable.

Friction and wear properties of three hard refractory coatings applied by radiofrequency sputtering

NASA Technical Reports Server (NTRS)

Brainard, W. A.

1977-01-01

The adherence, friction, and wear properties of thin hard refractory compound coatings applied to 440C bearing steel by radiofrequency sputtering were investigated. Friction and wear tests were done with nonconforming pin on disk specimens. The compounds examined were chromium carbide, molybdenum silicide, and titanium carbide. The adherence, friction, and wear were markedly improved by the application of a bias voltage to the bearing steel substrate during coating deposition. Analysis by X-ray photoelectron spectroscopy indicated that the improvement may be due to a reduction in impurities in bias deposited coatings. A fivefold reduction in oxygen concentration in MoSi2 coating by biasing was noted. Chromium carbide was not effective as an antiwear coating. Molybdenum silicide provided some reduction in both friction and wear. Titanium carbide exhibited excellent friction and antiwear properties at light loads. Plastic flow and transfer of the coating material onto the pin specimen appears to be important in achieving low friction and wear.

Efficacy of combined treatment with vacuum sealing drainage and recombinant human epidermal growth factor for refractory wounds in the extremities and its effect on serum levels of IL-6, TNF-α and IL-2

PubMed Central

Tan, Lei; Hou, Zhongyu; Gao, Yanzhi

2018-01-01

The objective of this study was to investigate the efficacy of combined treatment with vacuum sealing drainage (VSD) and recombinant human epidermal growth factor (rhEGF) for refractory wounds in the extremities, and its effect on serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-2. Ninety-eight patients with refractory wounds in the extremities were recruited and randomly divided into the combined treatment group (underwent VSD and rhEGF treatment) and control group (underwent VSD only) with 49 cases each. Formation of granulation tissue on the wound surface was assessed and scored. The wound healing rate was calculated after 1 week of treatment, and the time of complete healing was recorded. Serum levels of IL-6, IL-2, and TNF-α were measured using enzyme-linked immunosorbent assay. After 1 week of treatment, granulation tissue formation on wound surfaces was significantly improved (p<0.05) compared with that before treatment in both groups. Moreover, granulation tissue formation on wound surfaces was superior in the combined treatment group than in the control group (p<0.05). The wound healing rate was 63.50±4.75% in the combined treatment group and 31.79±3.52% in the control group, and the difference was statistically significant (p<0.05). The time of complete healing was 15.11±2.24 days in the combined treatment group and 19.63±2.76 days in the control group, and the difference was statistically significant (p<0.05). The serum levels of IL-6, IL-2, and TNF-α, in the two groups were significantly lower than those before treatment (p<0.05). Moreover, the levels in the combined treatment group were significantly lower than those in the control group (p<0.05). In conclusion, combined treatment with VSD and rhEGF reduced inflammation and shortened the time of complete healing of refractory wounds in the extremities. Measurement of the levels of related inflammatory factors provided a reference for the prognosis of refractory wounds. PMID:29250151

Percutaneous radiofrequency treatment for refractory anteromedial pain of osteoarthritic knees.

PubMed

Ikeuchi, Masahiko; Ushida, Takahiro; Izumi, Masashi; Tani, Toshikazu

2011-04-01

Although severe knee osteoarthritis with refractory pain is commonly treated surgically, this is often not an option for patients with poor health status or unwillingness to undergo major surgery. We examined the efficacy of radiofrequency application to sensory nerves as a novel alternative treatment for refractory knee pain. This study was an open-label, nonrandomized, and controlled study. Patients complaining of refractory anteromedial knee pain associated with radiological osteoarthritis (moderate or severe) were included. They were assigned to one of two groups: those receiving radiofrequency thermocoagulation (N = 18) or those receiving nerve block (N = 17), depending on the time period that they were referred to the clinic. Radiofrequency current or local anesthetics was applied to the medial retinacular nerve and the infrapatellar branch of the saphenous nerve. Western Ontario McMaster Universities osteoarthritis index score, pain visual analog scale (VAS), and patient's global assessment were assessed with a minimum follow-up of 6 months.   Radiofrequency treatment significantly decreased knee pain as measured by VAS for 12 weeks compared with the control group. In terms of responders, more patients in the RF group responded to the treatment than in the control group. The differences were statistically significant at 4 weeks, 8 weeks, and 12 weeks in pain VAS. Eight patients (44%) treated with radiofrequency rated excellent or good but only three (18%) in the control group rated good, although the difference was not statistically significant. Some patients were able to benefit substantially from radiofrequency treatment. Even if its effective period is limited, radiofrequency application is a promising treatment to alleviate refractory anteromedial knee pain with osteoarthritis. Further experience and technical improvements are needed to establish its role in the management of knee osteoarthritis. Wiley Periodicals, Inc.

Benefit from autologous stem cell transplantation in primary refractory myeloma? Different outcomes in progressive versus stable disease

PubMed Central

Rosiñol, Laura; García-Sanz, Ramón; Lahuerta, Juan José; Hernández-García, Miguel; Granell, Miquel; de la Rubia, Javier; Oriol, Albert; Hernández-Ruiz, Belén; Rayón, Consuelo; Navarro, Isabel; García-Ruiz, Juan Carlos; Besalduch, Joan; Gardella, Santiago; Jiménez, Javier López; Díaz-Mediavilla, Joaquín; Alegre, Adrián; Miguel, Jesús San; Bladé, Joan

2012-01-01

Background Several studies of autologous stem cell transplantation in primary refractory myeloma have produced encouraging results. However, the outcome of primary refractory patients with stable disease has not been analyzed separately from the outcome of patients with progressive disease. Design and Methods In the Spanish Myeloma Group 2000 trial, 80 patients with primary refractory myeloma (49 with stable disease and 31 with progressive disease), i.e. who were refractory to initial chemotherapy, were scheduled for tandem transplants (double autologous transplant or a single autologous transplant followed by an allogeneic transplant). Patients with primary refractory disease included those who never achieved a minimal response (≥25% M-protein decrease) or better. Responses were assessed using the European Bone Marrow Transplant criteria. Results There were no significant differences in the rates of partial response or better between patients with stable or progressive disease. However, 38% of the patients with stable disease at the time of transplantation remained in a stable condition or achieved a minimal response after transplantation versus 7% in the group with progressive disease (P=0.0017) and the rate of early progression after transplantation was significantly higher among the group with progressive disease at the time of transplantation (22% versus 2%; P=0.0043). After a median follow-up of 6.6 years, the median survival after first transplant of the whole series was 2.3 years. Progression-free and overall survival from the first transplant were shorter in patients with progressive disease (0.6 versus 2.3 years, P=0.00004 and 1.1 versus 6 years, P=0.00002, respectively). Conclusions Our results show that patients with progressive refractory myeloma do not benefit from autologous transplantation, while patients with stable disease have an outcome comparable to those with chemosensitive disease. (ClinicalTrials.gov:NCT00560053) PMID:22058223

Propofol Infusion Syndrome in Refractory Status Epilepticus

PubMed Central

Hwang, Woo Sub; Gwak, Hye Min; Seo, Dae-Won

2013-01-01

Background and Purpose: Propofol is used for treating refractory status epilepticus, which has high rate of mortality. Propofol infusion syndrome is a rare but often fatal syndrome, characterized by lactic acidosis, lipidemia, and cardiac failure, associated with propofol infusion over prolonged periods of time. We investigated the clinical factors that characterize propofol infusion syndrome to know the risk of them in refractory status epilepticus. Methods: This retrospective observation study was conducted in Samsung medical center from Jan. 2005 to Dec. 2009. Thirty two patients (19 males, 13 females, aged between 16 and 64 years), with refractory status epilepsy were included. Their clinical findings and treatment outcomes were evaluated retrospectively. We divided our patients into established status epilepticus (ESE) and refractory status epilepticus (RSE). And then the patients with RSE was further subdivided into propofol treatment group (RSE-P) and the other anesthetics treatment group (RSE-O). We analyzed the clinical characteristics by comparison of the groups. Results: There were significant differences of hypotension and lipid change between ESE and RSE (p<0.05). However, there was no significant difference between RSE-P and RSE-O groups. The hospital days were longer in RSE than in ESE (p=0.012) and treatment outcome was also worse in RSE than in ESE (p=0.007) but there were no significant differences of hospital stays and treatment outcome between RSE-P and RSE-O. Conclusions: RSE is very critical disease with high mortality, which may show as many clinical changes as propofol infusion syndrome. Therefore propofol infusion syndrome might be considered as one of the clinical manifestations of RSE. PMID:24649467

Tenon advancement and duplication technique to prevent postoperative Ahmed valve tube exposure in patients with refractory glaucoma.

PubMed

Tamcelik, Nevbahar; Ozkok, Ahmet; Sarıcı, Ahmet Murat; Atalay, Eray; Yetik, Huseyin; Gungor, Kivanc

2013-07-01

To present and compare the long-term results of Dr. Tamcelik's previously described technique of Tenon advancement and duplication with the conventional Ahmed glaucoma valve (AGV) implantation technique in patients with refractory glaucoma. This study was a multicenter, retrospective case series that included 303 eyes of 276 patients with refractory glaucoma who underwent glaucoma valve implantation surgery. The patients were divided into three groups according to the surgical technique applied and the outcomes compared. In group 1, 96 eyes of 86 patients underwent AGV implant surgery without patch graft; in group 2, 78 eyes of 72 patients underwent AGV implant surgery with donor scleral patch; in group 3, 129 eyes of 118 patients underwent Ahmed valve implant surgery with "combined short scleral tunnel with Tenon advancement and duplication technique". The endpoint assessed was tube exposure through the conjunctiva. In group 1, conjunctival tube exposure was seen in 11 eyes (12.9 %) after a mean 9.2 ± 3.7 years of follow-up. In group 2, conjunctival tube exposure was seen in six eyes (2.2 %) after a mean 8.9 ± 3.3 years of follow-up. In group 3, there was no conjunctival exposure after a mean 7.8 ± 2.8 years of follow-up. The difference between the groups was statistically significant. (P = 0.0001, Chi-square test). This novel surgical technique combining a short scleral tunnel with Tenon advancement and duplication was found to be effective and safe to prevent conjunctival tube exposure after AGV implantation surgery in patients with refractory glaucoma.

Midazolam fails to prevent neurological damage in children with convulsive refractory febrile status epilepticus.

PubMed

Nagase, Hiroaki; Nishiyama, Masahiro; Nakagawa, Taku; Fujita, Kyoko; Saji, Yohsuke; Maruyama, Azusa

2014-07-01

We conducted a retrospective study to compare the outcome of intravenous midazolam infusion without electroencephalography or targeted temperature management and barbiturate coma therapy with electroencephalography and targeted temperature management for treating convulsive refractory febrile status epilepticus. Of 49 consecutive convulsive refractory febrile status epilepticus patients admitted to the pediatric intensive care unit of our hospital, 29 were excluded because they received other treatments or because of various underlying illnesses. Thus, eight patients were treated with midazolam and 10 with barbiturate coma therapy using thiamylal. Midazolam-treated patients were intubated only when necessary, whereas barbiturate coma therapy patients were routinely intubated. Continuous electroencephalography monitoring was utilized only for the barbiturate coma group. The titration goal for anesthesia was clinical termination of status epilepticus in the midazolam group and suppression or burst-suppression patterns on electroencephalography in the barbiturate coma group. Normothermia was maintained using blankets and neuromuscular blockade in the barbiturate coma group and using antipyretics in the midazolam group. Prognoses were measured at 1 month after onset; children were classified into poor and good outcome groups. Good outcome was achieved in all the barbiturate coma group patients and 50% of the midazolam group patients (P = 0.02, Fisher's exact test). Although the sample size was small and our study could not determine which protocol element is essential for the neurological outcome, the findings suggest that clinical seizure control using midazolam without continuous electroencephalography monitoring or targeted temperature management is insufficient in preventing neurological damage in children with convulsive refractory febrile status epilepticus. Copyright © 2014 Elsevier Inc. All rights reserved.

Health-related quality of life in fibromyalgia and refractory angina pectoris: a comparison between two chronic non-malignant pain disorders.

PubMed

Andréll, Paulin; Schultz, Tomas; Mannerkorpi, Kaisa; Nordeman, Lena; Börjesson, Mats; Mannheimer, Clas

2014-04-01

To compare health-related quality of life in 2 different populations with chronic pain: patients with fibromyalgia and patients with refractory angina pectoris. Previous separate studies have indicated that these patient groups report different impacts of pain on health-related quality of life. The Short-Form 36 was used to assess health- related quality of life. In order to adjust for age and gender differences between the groups, both patient groups were compared with age- and gender-matched normative controls. The difference in health-related quality of life between the 2 patient groups was assessed by transforming the Short-Form 36 subscale scores to a z-score. The patients with fibromyalgia (n = 203) reported poorer health-related quality of life in all the subscale scores of Short-Form 36 (p < 0.05-0.0001) than the patients with refractory angina (n = 146) when both groups were compared with their corresponding normal population (z-score). Patients with fibromyalgia experience greater impairment in health-related quality of life compared with the normal population than do patients with refractory angina pectoris, despite the fact that the latter have a potentially life-threatening disease. The great impairment in health- related quality of life in patients with fibromyalgia should be taken into consideration when planning rehabilitation.

Selective adsorption for removal of nitrogen compounds from hydrocarbon streams over carbon-based adsorbents

NASA Astrophysics Data System (ADS)

Almarri, Masoud S.

The ultimate goal of this thesis is to develop a fundamental understanding of the role of surface oxygen functional groups on carbon-based adsorbents in the adsorption of nitrogen compounds that are known to be present in liquid fuels. N2 adsorption was used to characterize pore structures. The surface chemical properties of the adsorbents were characterized by X-ray photoelectron spectroscopy (XPS) and temperature-programmed desorption (TPD) techniques with a mass spectrometer to identify and quantify the type and concentration of oxygen functional groups on the basis of CO2 and CO evolution profiles. It was found that although surface area and pore size distribution are important for the adsorption process, they are not primary factors in the adsorption of nitrogen compounds. On the other hand, both the type and concentration of surface oxygen-containing functional groups play an important role in determining adsorptive denitrogenation performance. Higher concentrations of the oxygen functional groups on the adsorbents resulted in a higher adsorption capacity for the nitrogen compounds. A fundamental insight was gained into the contributions of different oxygen functional groups by analyzing the changes in the monolayer maximum adsorption capacity, qm, and the adsorption constant, K, for nitrogen compounds on different activated carbons. Acidic functional groups such as carboxylic acids and carboxylic anhydrides appear to contribute more to the adsorption of quinoline, while the basic oxygen functional groups such as carbonyls and quinones enhance the adsorption of indole. Despite the high number of publications on the adsorptive desulfurization of liquid hydrocarbon fuels, these studies did not consider the presence of coexisting nitrogen compounds. It is well-known that, to achieve ultraclean diesel fuel, sulfur must be reduced to a very low level, where the concentrations of nitrogen and sulfur compounds are comparable. The adsorptive denitrogenation and desulfurization of model diesel fuel, which contains equimolar concentrations of nitrogen (i.e., quinoline and indole), sulfur (i.e., dibenzothiophene and 4,6-dimethyldibenzothiophene), and aromatic compounds (naphthalene, 1-methylnaphthalene, and fluorene), was examined. The results revealed that when both nitrogen and sulfur compounds coexist in the fuel, the type and density of oxygen functional groups on the surface of the activated carbon are crucial for selective adsorption of nitrogen compounds but have negligible positive effects for sulfur removal. The adsorption of quinoline and indole is largely governed by specific interactions. There is enough evidence to support the importance of dipole--dipole and acid-base-specific interactions for the adsorption of both quinoline and indole. Modified carbon is a promising material for the efficient removal of the nitrogen compounds from light cycle oil (LCO). Adsorptive denitrogenation of LCO significantly improved the hydrodesulfurization (HDS) performance, especially for the removal of the refractory sulfur compounds such as 4-methyldibenzothiophene and 4,6-dimethyldibenzothiophene. An essential factor in applying activated carbon for adsorptive denitrogenation and desulfurization of liquid hydrocarbon streams is regeneration after saturation. The regeneration method of the saturated adsorbents consisted of toluene washing followed by heating to remove the remaining toluene. The results show that the spent activated carbon can be regenerated to completely recover the adsorption capacity. The high capacity and selectivity of activated carbon for nitrogen compounds, along with their ability to be regenerated, indicate that activated carbon is a promising adsorbent for the deep denitrogenation of liquid hydrocarbon streams.

Is refractory angina pectoris a form of chronic pain? A comparison of two patient groups receiving spinal cord stimulation therapy.

PubMed

Pak, Nick; Devcich, Daniel A; Johnson, Malcolm H; Merry, Alan F

2014-03-28

To compare psychological and pain-related characteristics of patients with chronic pain and patients with refractory angina pectoris who had been treated with spinal cord stimulation (SCS) therapy. Twenty-four patients receiving SCS therapy were interviewed. Four psychological variables were assessed using standardised questionnaires for pain catastrophising, health locus of control, anxiety sensitivity, and self-efficacy. Patients also completed the revised version of the Short-Form McGill Pain Questionnaire, the Short-Form Health Survey, and self-reported measures of global perceived effect, pain, functionality, and satisfaction with SCS therapy. Most patients reported improvements in pain, functionality, and improvement overall. Some health locus of control dimensions were significantly higher for the angina group than the chronic pain group, and chronic angina patients reported significantly lower levels of intermittent pain. Virtually all patients reported being satisfied with SCS therapy. Most self-rated psychological and pain-related characteristics were no different between the two groups, which gives some support to the view that refractory angina is a form of chronic pain. The results also add to evidence supporting the use of SCS therapy for refractory angina pectoris; however, differences observed on a few variables may indicate points of focus for the assessment and treatment of such patients.

The growth of Scenedesmus quadricauda in RO concentrate and the impacts on refractory organic matter, Escherichia coli, and trace organic compounds

EPA Science Inventory

This study achieves a better operational simplicity for the phycoremediation of reverse osmosis (RO) concentrate using Scenedesmus quadricauda microalgae. Under continuous illumination with CO2 supplementation, algal growth in the RO concentrate resulted in a conversion of polyme...

Colonic exclusion and combined therapy for refractory constipation.

PubMed

Peng, Hong-Yun; Xu, Ai-Zhong

2006-12-28

To investigate the therapeutic effectiveness of colonic exclusion and combined therapy for refractory constipation. Thirty-two patients with refractory constipation were randomly divided into treatment group (n = 14) and control group (n = 18). Fourteen patients in treatment group underwent colonic exclusion and end-to-side colorectal anastomosis. Eighteen patients in control group received subtotal colectomy and end-to-end colorectal anastomosis. The therapeutic effects of the operations were assessed by comparing the surgical time, incision length, volume of blood losses, hospital stay, recovery rate and complication incidence. All patients received long-term follow-up. All operations were successful and patients recovered fully after the operations. In comparison of treatment group and control group, the surgical time (h), incision length (cm), volume of blood losses (mL), hospital stay (d) were 87 +/- 16 min vs 194 +/- 23 min (t = 9.85), 10.4 +/- 0.5 cm vs 21.2 +/- 1.8 cm (t = 14.26), 79.5 +/- 31.3 mL vs 286.3 +/- 49.2 mL (t = 17.24), and 11.8 +/- 2.4 d vs 18.6 +/- 2.6 d (t = 6.91), respectively (P < 0.001 for all). The recovery rate and complication incidence were 85.7% vs 88.9% (P = 0.14 > 0.05), 21.4% vs 33.3% (P = 0.73 > 0.05), respectively. Colonic exclusion has better therapeutic efficacy on refractory constipation. It has many advantages such as shorter surgical time, smaller incision, fewer blood losses and shorter hospital stay.

Comparison of long-term outcomes between children with aplastic anemia and refractory cytopenia of childhood who received immunosuppressive therapy with antithymocyte globulin and cyclosporine.

PubMed

Hama, Asahito; Takahashi, Yoshiyuki; Muramatsu, Hideki; Ito, Masafumi; Narita, Atsushi; Kosaka, Yoshiyuki; Tsuchida, Masahiro; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

2015-11-01

The 2008 World Health Organization classification proposed a new entity in childhood myelodysplastic syndrome, refractory cytopenia of childhood. However, it is unclear whether this morphological classification reflects clinical outcomes. We retrospectively reviewed bone marrow morphology in 186 children (median age 8 years; range 1-16 years) who were enrolled in the prospective study and received horse antithymocyte globulin and cyclosporine between July 1999 and November 2008. The median follow-up period was 87 months (range 1-146 months). Out of 186 patients, 62 (33%) were classified with aplastic anemia, 94 (49%) with refractory cytopenia of childhood, and 34 (18%) with refractory cytopenia with multilineage dysplasia. Aplastic anemia patients received granulocyte colony-stimulating factor more frequently and for longer durations than other patients (P<0.01). After six months, response rates to immunosuppressive therapy were not significantly different among the 3 groups. Acquisition of chromosomal abnormalities was observed in 5 patients with aplastic anemia, 4 patients with refractory cytopenia of childhood, and 3 patients with refractory cytopenia with multilineage dysplasia. Although the cumulative incidence of total clonal evolution at ten years was not significantly different among the 3 groups, the cumulative incidence of monosomy 7 development was significantly higher in aplastic anemia than in the other groups (P=0.02). Multivariate analysis revealed that only granulocyte colony-stimulating factor administration duration of 40 days or more was a significant risk factor for monosomy 7 development (P=0.02). These findings suggest that even the introduction of a strict morphological distinction from hypoplastic myelodysplastic syndrome cannot eradicate clonal evolution in children with aplastic anemia. Copyright© Ferrata Storti Foundation.

Grain refinement in heavy rare earth element-free sintered Nd–Fe–B magnets by addition of a small amount of molybdenum

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

Kim, Jin Woo; Lee, Won Suk; Byun, Jong Min

2015-05-07

We employed a modified refractory-metal-addition method to achieve higher coercivity and remanence in heavy rare earth element (HREE)-free Nd–Fe–B sintered magnets. This process involved inducing the formation of a homogeneous secondary phase at the grain boundaries during sintering, making it possible to control the intergrain diffusion by adding small amounts of Mo, a refractory metal. To control the microstructure of the secondary phase effectively, a metal organic compound of the refractory metal was coated on the surfaces of the particles of an HREE-free Nd–Fe–B powder. The average grain size after this process was 5.60 μm, which was approximately 1.8 μm smaller thanmore » that of the HREE-free sintered Nd–Fe–B magnets (7.4 μm). The coercivity of the magnets prepared through this process could be increased from 11.88 kOe to 13.91 kOe without decreasing their remanence.« less

Basic refractory and slag management for petcoke carbon feedstock in gasifiers

DOEpatents

Kwong, Kyei-Sing; Bennett, James P; Nakano, Jinichiro

2014-04-22

The disclosure provides methods of operating a slagging gasifier using a carbon feedstock having a relatively high V.sub.2O.sub.5 to SiO.sub.2 ratio, such as petcoke. The disclosure generates a combined chemical composition in the feed mixture having less than 25 wt. % SiO.sub.2, greater than 20 wt. % V.sub.2O.sub.5, and greater than 20 wt. % CaO. The method takes advantage of a novel recognition that increased levels of SiO.sub.2 tend to decrease dissolution of the V.sub.2O.sub.3 which forms under the reducing conditions of the gasifier, and utilizes the CaO additive to establish a chemical phase equilibria comprised of lower melting compounds. The method further provides for control based on the presence of Al.sub.2O.sub.3 and FeO, and provides for a total combined chemical composition of greater than about 5 wt. % MgO for use with refractory linings comprised of MgO based refractory brick.

Cannabidiol as potential treatment in refractory pediatric epilepsy.

PubMed

Paolino, Maria Chiara; Ferretti, Alessandro; Papetti, Laura; Villa, Maria Pia; Parisi, Pasquale

2016-01-01

In recent years there has been great scientific and public interest focused on the therapeutic potential of compounds derived from cannabis for the treatment of refractory epilepsy in children. From in vitro and in vivo studies on animal models, cannabidiol (CBD) appears to be a promising anticonvulsant drug with a favorable side-effect profile. In humans, CBD efficacy and safety is not supported by well-designed trials and its use has been described by anecdotal reports. It will be necessary to investigate CBD safety, pharmacokinetics and interaction with other anti-epileptic drugs (AEDs) alongside performing double-blinded placebo-controlled trials in order to obtain conclusive data on its efficacy and safety in children.

Efficacy and Tolerability of Lacosamide in the Treatment of Children With Refractory Generalized Epilepsy.

PubMed

Miskin, Chandrabhaga; Khurana, Divya S; Valencia, Ignacio; Legido, Agustin; Hasbani, Daphne M; Carvalho, Karen S

2016-06-01

Lacosamide is FDA-approved in patients 17 years or older with partial-onset epilepsy. We evaluated the efficacy and tolerability of lacosamide in children with refractory generalized epilepsy. We retrospectively reviewed records of 21 children with refractory generalized epilepsy treated with lacosamide in our institution from 2009-2013 divided into 2 subgroups- I, Lennox-Gastaut Syndrome, and II, other generalized epilepsies. Efficacy was defined as seizure freedom or ≥50% seizure reduction. Descriptive data analysis including seizure freedom was compared using c(2) analysis. There were eleven females and ten males with a mean age, of 11.9 years. Five patients became seizure free, nine had ≥50% seizure reduction, and seven had no response. Group I: seven had ≥50% improvement, one did not respond. Group II: five became seizure free, two had ≥50% improvement, five had no response. Lacosamide is effective and well tolerated in children with refractory generalized epilepsy particularly patients with Lennox-Gastaut Syndrome. © The Author(s) 2016.

Rifaximin and midodrine improve clinical outcome in refractory ascites including renal function, weight loss, and short-term survival.

PubMed

Hanafy, Amr S; Hassaneen, Ahmad M

2016-12-01

The occurrence of refractory ascites in nearly 17% of patients with decompensated cirrhosis is an unresolved issue. Advanced liver disease, functional renal impairment, and vascular insensitivity to vasopressors are the main causes of its refractoriness. Therefore, the aim of this study was to evaluate the impact on diuresis, weight loss, and short-term survival if midodrine and rifaximin were added to the diuretic therapy (DT). The study evaluated the eligibility of 650 patients with cirrhosis and refractory ascites who were selected during the period from November 2011 to May 2015. A total of 50 patients were excluded and finally 600 were selected and divided into the following groups: patients exposed to DT (n=200) as a control group, or DT with midodrine and rifaximin group (n=400). Body weight, mean arterial pressure, and glomerular filtration rate were determined. Plasma renin and aldosterone were also determined. Follow-up was performed after 2, 6, and 12 weeks, and then every 2 months for 24 months. The mean arterial pressure was significantly higher in the midodrine and rifaximin group (P=0.000), and there was a highly significant weight loss after 12 weeks (12.5 kg) (P=0.000), a highly significant increase in serum sodium, urine output, and urinary sodium excretion (P=0.000), and creatinine clearance was more reduced in the control group. With rifaximin and midodrine, a complete response occurred in 310 (78%) patients, a partial response in 72 (18%), and no response in 18 (4%) versus 30 (15%), 110 (55%), and 60 (30%) in the control group, respectively (P=0.000). Midodrine and rifaximin significantly reduced paracentesis needs when compared with the controls (18 study patients vs. 75 DT-only patients, P=0.000). Adding rifaximin and midodrine to DT enhanced diuresis in refractory ascites with improved systemic, renal hemodynamics and short-term survival.

Loxoprofen sodium treatment for elderly men with refractory nocturia: effect on night-time urine production.

PubMed

Okada, Shinsuke; Watanabe, Hideki; Kojima, Yoshiyuki; Yanai, Yoshimasa; Sasaki, Shoichi; Kohri, Kenjiro

2008-05-01

We evaluated the efficacy of loxoprofen sodium for refractory nocturia. Twelve men (mean age, 75.1 +/- 5.7) with nocturia were enrolled in this study. All patients received 60 mg loxoprofen sodium prior to sleeping at night for 14 days. Nine of 12 patients (75%) felt more satisfaction than previous treatments. Patients were grouped into a loxoprofen sodium-effective (n = 7) and ineffective groups (n = 5) based on the results of the frequency-volume chart. In the effective group, interestingly, night-time urine volume showed significant reduction (P < 0.05). On the other hand, the average single voided volume at night and 24-h urine volume showed no significant change. There was a statistically significant difference in the night-time urine volume after treatment between groups (P < 0.01). Loxoprofen sodium is an effective treatment for some patients with refractory nocturia. The main effect mechanism of loxoprofen sodium may involve the reduction of night-time urine production.

A RELICT Spinel Grain in an Allende Ferromagnesian Chondrule

NASA Astrophysics Data System (ADS)

Misawa, K.; Fujita, T.; Kitamura, M.; Nakamura, N.; Yurimoto, H.

1993-07-01

It is suggested that one of the refractory lithophile precursors in CV-CO chondrules was a hightemperature condensate from the nebular gas and was related to Ca,Al-rich inclusions (CAIs) [1-3]. However, little is known about refractory siderophile precursors in chondrules [4]. Allende barred olivine chondrule R-11 consists mainly of olivine (Fa(sub)7- 18), pyroxene (En(sub)93Fs(sub)1Wo(sub)6, En(sub)66Fs(sub)1Wo(sub)33), plagioclase (An(sub)80), Fe-poor spinel, and alkali-rich glass. The CI- chondrite normalized REE pattern of the chondrule, excluding a spinel grain, are fractionated, HREEdepleted (4.6-7.8 x CI) with a large positive Yb anomaly. The REE abundances are hump-shaped functions of elemental volatility, moderately refractory REE-enriched, suggesting that the refractory lithophile precursor component of R-11 could be a condensate from the nebular gas and related to Group 11 CAIs [1,2]. An interior portion of spinel is almost Fe-free, but in an outer zone (2040 micrometers in width) FeO contents increase rapidly. TiO(sub)2, Cr(sub)2O(sub)3, and V(sub)2O(sub)3 contents in core spinel are less than 0.5%, which is different from the V-rich nature of spinel in fluffy Type A CAIs [5]. The Fe-Mg zoning of spinel may have been generated by diffusional emplacement of Mg and Fe during chondrule-forming events. The spinel contains silicate inclusions and tiny metallic grains. The largest silicate inclusion is composed of Al,Ti-rich pyroxene and Ak 40 melilite. One of the submicrometersized grains was analyzed by SEM-EDS and found to be composed of refractory Pt-group metals with minor amounts of Fe and Ni. This is the first occurrence of refractory Pt-group metal nuggets in a ferromagnesian chondrule from the Allende meteorite. Tungsten, Os, Ir, Mo, and Ru are enriched 2-6 x 10^5 relative to CIs, and abundances of Pt and Rh decrease 2-10 x 10^4 with increasing volatility. In addition, abundances of Fe and Ni in the nugget are equal to or less than that CI chondrites. A depletion of Mo relative to other refractory metals may have resulted from high- temperature oxidation [6]. Chondrule R-11 exhibits both similarities (spinel and plagioclase chemistry; Group II REE pattern) and differences (fassaite chemistry; existence of refractory Pt-group metal nuggets and melilite) with respect to POIs [3] carrying isotopically fractionated Mg. Refractory Pt-group metal nuggets in CAIs are considered to have been produced during high-temperature events (at least 1300 degrees C) before total condensation of Fe in the early solar nebula [8-10]. In analogy with the formation history with CAIs, we suggest that one of the refractory siderophile precursor components of Allende chondrules is a high-temperature condensate from the nebular gas and is associated with refractory oxide and silicates. References: [1] Misawa K. and Nakamura N. (1988) GCA, 52, 1669. [2] Misawa K. and Nakamura N. (1988) Nature, 334, 47. [3] Sheng Y. J. et al. (1991) GCA, 55, 581. [4] Grossman J. N. et al. (1988) In Meteorites and the Early Solar System (J. F. Kerridge and M. S. Matthews, eds.), 619, Univ. of Arizona. [5] MacPherson G. J. and Grossman L. (1984) GCA, 48, 29. [6] Fegley B. Jr. and Palme H. (1985) EPSL, 72, 311. [7] Wark D. A. and Lovering J. F. (1976) LS VII, 912. [8] Palme H. and Wlotzka F. (1976) EPSL, 33, 45. [9] El Goresy A. et al. (1978) Proc. LPSC 9th, 1279. [10] Blander M. and Fuchs L. H. (1980) Proc. LPSC 11th, 929.

Effect of Rice Husk Ash Insulation Powder on the Reoxidation Behavior of Molten Steel in Continuous Casting Tundish

NASA Astrophysics Data System (ADS)

Kim, Tae Sung; Chung, Yongsug; Holappa, Lauri; Park, Joo Hyun

2017-06-01

Rice husk ash (RHA) has been widely used as an insulation powder in steel casting tundish. Its effect on the reoxidation of molten steel in tundish as well as on the corrosion of magnesia refractory was investigated. The reoxidation of the steel, indicated by an oxygen pickup, was progressed by increasing the ratio of RHA to the sum of RHA and carryover ladle slag ( R ratio) greater than about 0.2. The increase of the silica activity in the slag layer promoted the self-dissociation of SiO2 from the slag layer into the molten steel, resulting in the silicon and oxygen pickup as the R ratio increased. The total number of reoxidation inclusions dramatically increased and the relative fraction of Al2O3-rich inclusions increased by increasing the R ratio. Hence, the reoxidation of molten steel in tundish might become more serious due to the formation of alumina-rich inclusions as the casting sequence increases. MgO in the refractory directly dissolved into the molten slag layer without forming any intermediate compound layer ( e.g., spinel), which is a completely different situation from the general slag-refractory interfacial reaction. A flow was possibly induced by the bursting of gas bubbles at the ash-slag (-refractory) interface, since the silica in the RHA powder continuously dissolved into the molten slag pool. Thus, the RHA insulation powder has a negative effect on the corrosion of MgO refractory.

Pro-osteogenic effects of fibrin glue in treatment of avascular necrosis of the femoral head in vivo by hepatocyte growth factor-transgenic mesenchymal stem cells

PubMed Central

2014-01-01

Background Autologous transplantation of modified mesenchymal stem cells (MSCs) is a promising candidate for the treatment of the refractory clinical disease, avascular necrosis of the femoral head (ANFH). Our previous attempts by compounding MSCs with medical fibrin glue to treat ANFH in animal model have achieved excellent effects. However, the underlying molecular mechanism is unclear, especially on the transgenic gene expression. Methods Rabbit MSCs were isolated and compounded with fibrin glue. Following degrading of fibrin glue, proliferation, viability, expression of transgenic hepatocyte growth factor gene as well as osteogenic differentiation of MSCs were evaluated together with that of uncompounded MSCs. Fibrin glue-compounded MSCs were transplanted into the lesion of ANFH model, and the therapeutic efficacy was compared with uncompounded MSCs. One-Way ANOVA was used to determine the statistical significance among treatment groups. Results Fibrin glue compounding will not affect molecular activities of MSCs, including hepatocyte growth factor (HGF) secretion, cell proliferation and viability, and osteogenic differentiation in vitro. When applying fibrin glue-compounded MSCs for the therapy of ANFH in vivo, fibrin glue functioned as a drug delivery system and provided a sustaining microenvironment for MSCs which helped the relatively long-term secretion of HGF in the femoral head lesion and resulted in improved therapeutic efficacy when compared with uncompounded MSCs as indicated by hematoxylin-eosin staining and immunohistochemistry of osteocalcin, CD105 and HGF. Conclusion Transplantation of fibrin glue-compounding MSCs is a promising novel method for ANFH therapy. PMID:24885252

Pelvic drainage during removal of dialysis catheter decreases the risk of subsequent intra-abdominal complications in refractory peritoneal dialysis-related peritonitis.

PubMed

Hsu, Chih-Yang; Huang, Wei-Chieh; Huang, Chun-Kai; Huang, Chien-Wei; Chou, Nan-Hua; Lee, Po-Tsang; Fang, Hua-Chang; Chou, Kang-Ju; Chen, Chien-Liang

2015-11-01

Some patients with refractory peritoneal dialysis-related peritonitis continue to develop intra-abdominal complications despite removal of the peritoneal catheter. Repeated percutaneous drainage or open laparotomy is often required, and mortality is not uncommon. The benefits of pelvic drainage placement during catheter removal in decreasing these complications and interventions remain unproven. Forty-six patients with refractory peritonitis who underwent removal of a Tenckhoff catheter between 1991 and 2013 were reviewed retrospectively. Twelve patients had pelvic drainage using closed active suction devices during catheter removal (drainage group). The remaining 34 patients underwent catheter removal without drainage (non-drainage group). The outcomes measured were the development of intra-abdominal complications and the requirement for repeated percutaneous drainage or open laparotomy within 90 days after the catheter removal. Baseline characteristics were similar with the exception of a higher median number of previous peritonitis episodes in the drainage group compared with the non-drainage group (2 vs 0, P = 0.02). During the follow-up period, intra-abdominal complications occurred in 15 (44%) of 34 patients in the non-drainage group, compared with one (8%) of 12 patients in the drainage group (P = 0.03). Twelve (35%) patients in the non-drainage group required repeated percutaneous drainage or open laparotomy for management, compared with zero (0%) patients in the drainage group (P = 0.02). Drain tubes were removed at a median of 6 days (inter-quartile range: 5-10) without complications. In the management of refractory peritonitis, pelvic drainage during removal of dialysis catheter decreases the risk of subsequent intra-abdominal complications and invasive interventions. © 2015 Asian Pacific Society of Nephrology.

Characteristics, sources and evolution of fine aerosol (PM1) at urban, coastal and forest background sites in Lithuania

NASA Astrophysics Data System (ADS)

Masalaite, A.; Holzinger, R.; Remeikis, V.; Röckmann, T.; Dusek, U.

2017-01-01

The chemical and isotopic composition of organic aerosol (OA) samples collected on PM1 filters was determined as a function of desorption temperature to investigate the main sources of organic carbon and the effects of photochemical processing on atmospheric aerosol. The filter samples were collected at an urban (54°38‧ N, 25°18‧ E), coastal (55°55‧ N, 21°00‧ E) and forest (55°27‧ N, 26°00' E) site in Lithuania in March 2013. They can be interpreted as winter-time samples because the monthly averaged temperature was -4 °C. The detailed chemical composition of organic compounds was analysed with a thermal desorption PTR-MS. The mass concentration of organic aerosol at the forest site was roughly by a factor of 30 lower than at the urban and coastal site. This fact could be an indication that in this cold month the biogenic secondary organic aerosol (SOA) formation was very low. Moreover, the organic aerosol collected at the forest site was more refractory and contained a larger fraction of heavy molecules with m/z > 200. The isotopic composition of the aerosol was used to differentiate the two main sources of organic aerosol in winter, i.e. biomass burning (BB) and fossil fuel (FF) combustion. Organic aerosol from biomass burning is enriched in 13C compared to OA from fossil fuel emissions. δ13COC values of the OA samples showed a positive correlation with the mass fraction of several individual organic compounds. Most of these organic compounds contained nitrogen indicating that organic nitrogen compounds formed during the combustion of biomass may be indicative of BB. Other compounds that showed negative correlations with δ13COC were possibly indicative of FF. These compounds included heavy hydrocarbons and were on the average less oxidized than the bulk organic carbon. The correlation of δ13COC and the O/C ratio was positive at low but negative at high desorption temperatures at the forest site. We propose that this might be due to photochemical processing of OA. This processing can lead to accumulation of carbon in the more refractory organic fraction that is depleted in 13C compared with the less refractory organic fraction. Detailed laboratory experiments are necessary to further investigate the aging of aerosol particles before firm conclusions can be drawn.

Supported molten-metal catalysts

DOEpatents

Datta, Ravindra; Singh, Ajeet; Halasz, Istvan; Serban, Manuela

2001-01-01

An entirely new class of catalysts called supported molten-metal catalysts, SMMC, which can replace some of the existing precious metal catalysts used in the production of fuels, commodity chemicals, and fine chemicals, as well as in combating pollution. SMMC are based on supporting ultra-thin films or micro-droplets of the relatively low-melting (<600.degree. C.), inexpensive, and abundant metals and semimetals from groups 1, 12, 13, 14, 15 and 16, of the periodic table, or their alloys and intermetallic compounds, on porous refractory supports, much like supported microcrystallites of the traditional solid metal catalysts. It thus provides orders of magnitude higher surface area than is obtainable in conventional reactors containing molten metals in pool form and also avoids corrosion. These have so far been the chief stumbling blocks in the application of molten metal catalysts.

Low-cost industrially available molybdenum boride and carbide as "platinum-like" catalysts for the hydrogen evolution reaction in biphasic liquid systems.

PubMed

Scanlon, Micheál D; Bian, Xiaojun; Vrubel, Heron; Amstutz, Véronique; Schenk, Kurt; Hu, Xile; Liu, BaoHong; Girault, Hubert H

2013-02-28

Rarely reported low-cost molybdenum boride and carbide microparticles, both of which are available in abundant quantities due to their widespread use in industry, adsorb at aqueous acid-1,2-dichloroethane interfaces and efficiently catalyse the hydrogen evolution reaction in the presence of the organic electron donor - decamethylferrocene. Kinetic studies monitoring biphasic reactions by UV/vis spectroscopy, and further evidence provided by gas chromatography, highlight (a) their superior rates of catalysis relative to other industrially significant transition metal carbides and silicides, as well as a main group refractory compound, and (b) their highly comparable rates of catalysis to Pt microparticles of similar dimensions. Insight into the catalytic processes occurring for each adsorbed microparticle was obtained by voltammetry at the liquid-liquid interface.

Refractory Materials for Flame Deflector Protection System Corrosion Control: Refractory Ceramics Literature Survey

NASA Technical Reports Server (NTRS)

Calle, Luz Marina; Hintze, Paul E.; Parlier, Christopher R.; Curran, Jerome P.; Kolody, Mark; Perusich, Stephen; Whitten, Mary C.; Trejo, David; Zidek, Jason; Sampson, Jeffrey W.;

All NbN tunnel junction fabrication

NASA Technical Reports Server (NTRS)

Leduc, H. G.; Khanna, S. K.; Stern, J. A.

1987-01-01

The development of SIS tunnel junctions based on NbN for mixer applications in the submillimeter range is reported. The unique technological challenges inherent in the development of all refractory-compound superconductor-based tunnel junctions are highlighted. Current deposition and fabrication techniques are discussed, and the current status of all-NbN tunnel junctions is reported.

Transmission electron microscopy: direct observation of crystal structure in refractory ceramics.

PubMed

Shaw, T M; Thomas, G

1978-11-10

Using high-resolution multibeam interference techniques in the transmission electron microscope, images have been obtained that make possible a real-space structure analysis of a beryllium-silicon-nitrogen compound. The results illustrate the usefulness of lattice imaging in the analysis of local crystal structure in these technologically promising ceramic materials.

Degradation of refractory organics in biotreated landfill leachate using high voltage pulsed discharge combined with TiO2.

PubMed

Zhang, Cheng; Liu, Jianyong; Yang, Xiaojian; Cao, Weimin; Qian, Guangren

2017-03-15

The effect of high voltage pulsed discharge (HVPD) combined with TiO 2 on the degradation of refractory organic compounds in actual biotreated landfill leachate was investigated. The optimal chemical oxygen demand (COD) removal efficiency could achieve to 58.9% using HVPD+TiO 2 within 30min at 40kV, 400Hz, and the conductivity of 4.05mscm -1 in gas-liquid pulsed discharge. The aromatic compounds decreased by 33.6% compared with HVPD alone according to the UV absorbance at 254nm. Moreover, the fluorescence intensity of humic and fulvic substances was greatly decreased. Active species such as OH radical and H 2 O 2 were enhanced in the presence of TiO 2 , resulting in more high molecular weight organic matter into small molecules or mineralized. In addition, possible degradation pathways was proposed based on acetophenone, which is effective for the degradation of organic matter in biotreated landfill leachate as long as the active species increased. Copyright © 2016 Elsevier B.V. All rights reserved.

SAR202 Genomes from the Dark Ocean Predict Pathways for the Oxidation of Recalcitrant Dissolved Organic Matter

PubMed Central

Landry, Zachary; Swan, Brandon K.; Herndl, Gerhard J.; Stepanauskas, Ramunas

2017-01-01

ABSTRACT Deep-ocean regions beyond the reach of sunlight contain an estimated 615 Pg of dissolved organic matter (DOM), much of which persists for thousands of years. It is thought that bacteria oxidize DOM until it is too dilute or refractory to support microbial activity. We analyzed five single-amplified genomes (SAGs) from the abundant SAR202 clade of dark-ocean bacterioplankton and found they encode multiple families of paralogous enzymes involved in carbon catabolism, including several families of oxidative enzymes that we hypothesize participate in the degradation of cyclic alkanes. The five partial genomes encoded 152 flavin mononucleotide/F420-dependent monooxygenases (FMNOs), many of which are predicted to be type II Baeyer-Villiger monooxygenases (BVMOs) that catalyze oxygen insertion into semilabile alicyclic alkanes. The large number of oxidative enzymes, as well as other families of enzymes that appear to play complementary roles in catabolic pathways, suggests that SAR202 might catalyze final steps in the biological oxidation of relatively recalcitrant organic compounds to refractory compounds that persist. PMID:28420738

[Dust and silica exposure on metallurgical furnace maintenance using refractory materials].

PubMed

Garattini, S; Barbieri, P G; Bottone, F; Brunelli, E; Carminati, F; Chiari, R; Sarnico, M

2012-01-01

In the metallurgical industries the silica risk has long been known, particularly for the refractoryes maintenance workers. The maintenance of furnaces, ladles and tundisches refractory linings, on the current organization of production, is provided by companies under contract. The information available about the characterization of risk for this group of workers are at present inadequate. The study investigates the exposure to dust, also containing free crystalline silica (SLC), through the analysis of samples of commercial products used in the reconstruction of refractory linings of furnaces, ladles and tundisches, materials from the demolition of refractory articles and dust from work areas. It also presents the results of an environmental investigation conducted during the demolition and reconstruction of the refractory in three steel mills. The Authors, by the numerous inspections and the systematic survey of working conditions, have formulated a SLC risk profile and some proposals for prevention.

Low-Dose Naltrexone: A New Therapy Option for Complex Regional Pain Syndrome Type I Patients.

PubMed

Sturn, Kayla M; Collin, Michael

2016-01-01

Naltrexone (an opioid antagonist) has long been used in patients overcoming alcohol and opioid dependency. However, at doses one-tenth of those commonly prescribed for the above conditions, an unexpected effect occurs that aids in alleviating pain. Although there are currently no randomized clinical trials supporting the use of low-dose naltrexone, we present a case study describing the impact of compounding low-dose naltrexone that has dramatically improved the patient's pain symptoms which were refractory to other treatments. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Effects of various additives on sintering of aluminum nitride

NASA Technical Reports Server (NTRS)

Komeya, K.; Inoue, H.; Tsuge, A.

1982-01-01

Effects of thirty additives on sintering A/N were investigated. The addition of alkali earth oxides and rare earth oxides gave fully densified aluminum nitride. This is due to the formation of nitrogen-containing aluminate liquid in the system aluminum nitride-alkali earth oxides or rare earth oxides. Microstructural studies of the sintered specimens with the above two types of additives suggested that the densification was due to the liquid phase sintering. Additions of silicon compounds resulted in poor densification by the formation of highly refractory compounds such as A/N polytypes.

Occurrence of emerging pollutants in urban wastewater and their removal through biological treatment followed by ozonation.

PubMed

Rosal, Roberto; Rodríguez, Antonio; Perdigón-Melón, José Antonio; Petre, Alice; García-Calvo, Eloy; Gómez, María José; Agüera, Ana; Fernández-Alba, Amadeo R

2010-01-01

This work reports a systematic survey of over seventy individual pollutants in a Sewage Treatment Plant (STP) receiving urban wastewater. The compounds include mainly pharmaceuticals and personal care products, as well as some metabolites. The quantification in the ng/L range was performed by Liquid Chromatography-QTRAP-Mass Spectrometry and Gas Chromatography coupled to Mass Spectrometry. The results showed that paraxanthine, caffeine and acetaminophen were the main individual pollutants usually found in concentrations over 20 ppb. N-formyl-4-amino-antipiryne and galaxolide were also detected in the ppb level. A group of compounds including the beta-blockers atenolol, metoprolol and propanolol; the lipid regulators bezafibrate and fenofibric acid; the antibiotics erythromycin, sulfamethoxazole and trimethoprim, the antiinflammatories diclofenac, indomethacin, ketoprofen and mefenamic acid, the antiepileptic carbamazepine and the antiacid omeprazole exhibited removal efficiencies below 20% in the STP treatment. Ozonation with doses lower than 90 microM allowed the removal of many individual pollutants including some of those more refractory to biological treatment. A kinetic model allowed the determination of second order kinetic constants for the ozonation of bezafibrate, cotinine, diuron and metronidazole. The results show that the hydroxyl radical reaction was the major pathway for the oxidative transformation of these compounds. (c) 2009 Elsevier Ltd. All rights reserved.

“Combined Occlusion and Atropine Therapy” Versus “Augmented Part-Time Patching” in Children with Refractory/Residual Amblyopia: A Pilot Study

PubMed Central

Sachdeva, Virender; Mittal, Vaibhev; Gupta, Varun; Gunturu, Rekha; Kekunnaya, Ramesh; Chandrasekharan, Anjali; Chabblani, Preeti Patil; Rao, Harsha L.

2016-01-01

Purpose: To compare the efficacy of combined occlusion and atropine therapy (COAT) and augmented part-time patching for the treatment of unilateral refractory/residual amblyopia. Methodology: This retrospective study evaluated children between 4 and 11 years with refractory/residual amblyopia who were treated with either additional atropine (COAT group) or increased hours of patching (augmented group). Data were collected on improvement in best-corrected visual acuity (BCVA; logarithm of the minimum angle of resolution [logMAR] units) at each follow-up visit. Results: There were 19 children in the COAT group and 17 children in the augmented group. The baseline BCVA of the amblyopic eye was 0.79 ± 0.36 logMAR in the COAT group and 0.72 ± 0.26 logMAR in augmented group. Children were statistically significantly younger in the COAT group (6.4 ± 2.2 years) compared to the augmented group (8.6 ± 3.3 years, P = 0.02). The mean duration of follow-up was statistically significantly longer in the augmented group (20.2 COAT group; 13.9 months augmented group) (P = 0.03). Compliance was similar in both groups. LogMAR BCVA (adjusted for difference in age and baseline BCVA) was statistically significantly better in the COAT group (0.56 ± 0.04) compared to the augmented group (0.80 ± 0.04) at 3 months (P = 0.000); 6 months (COAT group, 0.50 ± 0.04 vs. augmented group, 0.74 ± 0.04; P = 0.04) and at 1 year (COAT group, 0.42 ± 0.04 vs. augmented group, 0.67 ± 0.04, P = 0.000). There was statistically significantly greater improvement in logMAR BCVA at 6 months in COAT group (0.26 ± 0.15) compared to the augmented group (0.02 ± 0.14), (P = 0.0002). Age, gender, pretreatment BCVA, duration of follow-up, or compliance to patching did not affect improvement in BCVA. Conclusions: COAT may result in greater improvement in BCVA than augmented part-time patching in children with unilateral residual/refractory amblyopia. PMID:27162453

"Combined Occlusion and Atropine Therapy" Versus "Augmented Part-Time Patching" in Children with Refractory/Residual Amblyopia: A Pilot Study.

PubMed

Sachdeva, Virender; Mittal, Vaibhev; Gupta, Varun; Gunturu, Rekha; Kekunnaya, Ramesh; Chandrasekharan, Anjali; Chabblani, Preeti Patil; Rao, Harsha L

2016-01-01

To compare the efficacy of combined occlusion and atropine therapy (COAT) and augmented part-time patching for the treatment of unilateral refractory/residual amblyopia. This retrospective study evaluated children between 4 and 11 years with refractory/residual amblyopia who were treated with either additional atropine (COAT group) or increased hours of patching (augmented group). Data were collected on improvement in best-corrected visual acuity (BCVA; logarithm of the minimum angle of resolution [logMAR] units) at each follow-up visit. There were 19 children in the COAT group and 17 children in the augmented group. The baseline BCVA of the amblyopic eye was 0.79 ± 0.36 logMAR in the COAT group and 0.72 ± 0.26 logMAR in augmented group. Children were statistically significantly younger in the COAT group (6.4 ± 2.2 years) compared to the augmented group (8.6 ± 3.3 years, P = 0.02). The mean duration of follow-up was statistically significantly longer in the augmented group (20.2 COAT group; 13.9 months augmented group) (P = 0.03). Compliance was similar in both groups. LogMAR BCVA (adjusted for difference in age and baseline BCVA) was statistically significantly better in the COAT group (0.56 ± 0.04) compared to the augmented group (0.80 ± 0.04) at 3 months (P = 0.000); 6 months (COAT group, 0.50 ± 0.04 vs. augmented group, 0.74 ± 0.04; P = 0.04) and at 1 year (COAT group, 0.42 ± 0.04 vs. augmented group, 0.67 ± 0.04, P = 0.000). There was statistically significantly greater improvement in logMAR BCVA at 6 months in COAT group (0.26 ± 0.15) compared to the augmented group (0.02 ± 0.14), (P = 0.0002). Age, gender, pretreatment BCVA, duration of follow-up, or compliance to patching did not affect improvement in BCVA. COAT may result in greater improvement in BCVA than augmented part-time patching in children with unilateral residual/refractory amblyopia.

Physiotherapy, and speech and language therapy intervention for patients with refractory chronic cough: a multicentre randomised control trial.

PubMed

Chamberlain Mitchell, Sarah A F; Garrod, Rachel; Clark, Lynne; Douiri, Abdel; Parker, Sean M; Ellis, Jenny; Fowler, Stephen J; Ludlow, Siobhan; Hull, James H; Chung, Kian Fan; Lee, Kai K; Bellas, H; Pandyan, Anand; Birring, Surinder S

2017-02-01

Physiotherapy, and speech and language therapy are emerging non-pharmacological treatments for refractory chronic cough. We aimed to investigate the efficacy of a physiotherapy, and speech and language therapy intervention (PSALTI) to improve health-related quality of life (HRQoL) and to reduce cough frequency in patients with refractory chronic cough. In this multicentre randomised controlled trial, patients with refractory chronic cough were randomised to four weekly 1:1 sessions of either PSALTI consisting of education, laryngeal hygiene and hydration, cough suppression techniques, breathing exercises and psychoeducational counselling or control intervention consisting of healthy lifestyle advice. We assessed the change in HRQoL at week 4 with the Leicester Cough Questionnaire (LCQ). Secondary efficacy outcomes included 24-hour objective cough frequency (Leicester Cough Monitor) and cough reflex sensitivity. The primary analysis used an analysis of covariance adjusted for baseline measurements with the intention-to-treat population. This study was registered at UK Clinical Research Network (UKCRN ID 10678). Between December 2011 and April 2014, we randomly assigned 75 participants who underwent baseline assessment (34 PSALTI and 41 controls). In the observed case analysis, HRQoL (LCQ) improved on average by 1.53 (95% CI 0.21 to 2.85) points more in PSALTI group than with control (p=0.024). Cough frequency decreased by 41% (95% CI 36% to 95%) in PSALTI group relative to control (p=0.030). The improvements within the PSALTI group were sustained up to 3 months. There was no significant difference between groups in the concentration of capsaicin causing five or more coughs. Greater improvements in HRQoL and cough frequency were observed with PSALTI intervention. Our findings support the use of PSALTI for patients with refractory chronic cough. UKCRN ID 10678 and ISRCTN 73039760; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Managing cardiac arrest with refractory ventricular fibrillation in the emergency department: Conventional cardiopulmonary resuscitation versus extracorporeal cardiopulmonary resuscitation.

PubMed

Siao, Fu-Yuan; Chiu, Chun-Chieh; Chiu, Chun-Wen; Chen, Ying-Chen; Chen, Yao-Li; Hsieh, Yung-Kun; Lee, Chien-Hui; Wu, Chang-Te; Chou, Chu-Chung; Yen, Hsu-Heng

2015-07-01

Refractory ventricular fibrillation, resistant to conventional cardiopulmonary resuscitation (CPR), is a life threatening rhythm encountered in the emergency department. Although previous reports suggest the use of extracorporeal CPR can improve the clinical outcomes in patients with prolonged cardiac arrest, the effectiveness of this novel strategy for refractory ventricular fibrillation is not known. We aimed to compare the clinical outcomes of patients with refractory ventricular fibrillation managed with conventional CPR or extracorporeal CPR in our institution. This is a retrospective chart review study from an emergency department in a tertiary referral medical center. We identified 209 patients presenting with cardiac arrest due to ventricular fibrillation between September 2011 and September 2013. Of these, 60 patients were enrolled with ventricular fibrillation refractory to resuscitation for more than 10 min. The clinical outcome of patients with ventricular fibrillation received either conventional CPR, including defibrillation, chest compression, and resuscitative medication (C-CPR, n = 40) or CPR plus extracorporeal CPR (E-CPR, n = 20) were compared. The overall survival rate was 35%, and 18.3% of patients were discharged with good neurological function. The mean duration of CPR was longer in the E-CPR group than in the C-CPR group (69.90 ± 49.6 min vs 34.3 ± 17.7 min, p = 0.0001). Patients receiving E-CPR had significantly higher rates of sustained return of spontaneous circulation (95.0% vs 47.5%, p = 0.0009), and good neurological function at discharge (40.0% vs 7.5%, p = 0.0067). The survival rate in the E-CPR group was higher (50% vs 27.5%, p = 0.1512) at discharge and (50% vs 20%, p = 0. 0998) at 1 year after discharge. The management of refractory ventricular fibrillation in the emergency department remains challenging, as evidenced by an overall survival rate of 35% in this study. Patients with refractory ventricular fibrillation receiving E-CPR had a trend toward higher survival rates and significantly improved neurological outcomes than those receiving C-CPR. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

[Esophageal motility characteristics of refractory heartburn: a study based on high resolution manometry and 24 hour pH-impedance monitoring].

PubMed

Wang, Kun; Duan, Liping; Xia, Zhiwei; Xu, Zhijie; Ge, Ying

2014-09-16

To analyze the esophageal motility characteristics of refractory heartburn with different reflux patterns and preliminarily clarify the roles of esophageal disorder in refractory heartburn. A total of 176 refractory heartburn patients were enrolled from 2009 to 2013. After gastroscopy and 24 hour pH-impedance monitoring, they were divided into 4 groups of reflux esophagitis (RE, n = 29), non-erosive reflux disease with acid reflux (NERD-acid, n = 51), NERD with weakly acidic reflux (NERD-weakly acid, n = 51) and non-reflux associated heartburn (n = 45). All subjects undertake high resolution manometry test and their esophageal motility functions were analyzed by the Chicago classification criteria 2012. Among them, 60.23% (106/176) patients presented esophageal motility disorders. And 42.61% (75/176) fulfilled the criteria of weak peristalsis, 7.39% (13/176) distal esophageal spasm, 4.55% (8/176) rapid contraction, 3.98% (7/176) EGJ outflow obstruction, 1.14% (2/176) hiatus hernia and 1 Jackhammer esophagus. The detection rates of esophageal motility disorder were similar among 4 groups and weak peristalsis was the most common disorder in all groups (41.38% in RE, 37.25% in NERD-acid patients, 54.90% in NERD-weakly acid and 35.56% in non-reflux associated heartburn patients). However, hypertensive motility disorders in non-reflux associated heartburn group (31.11%, 14/45) were more than GERD subgroups (11.45%, 15/131) (P < 0.05) . The relax ratio of low esophagus sphincter (LES) in GERD subgroups were higher than that in non-reflux associated heartburn patients. And the relax ratio of NERD-weakly acid was significantly higher than that in non-reflux associated heartburn patients (65% (50%-80%) vs 58% (42%-67%) , P < 0.05). The integrated relaxation pressure in GERD subgroups were lower than that of non-reflux associated heartburn patients without significant differences (P > 0.05). Esophageal weak peristalsis is one of the most common motility disorders in refractory heartburn patients, and esophageal hypertensive motility disorders are common in non-reflux associated heartburn patients. Esophageal manometry is necessary for the diagnosis and treatment of refractory heartburn.

Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma

PubMed Central

Weisel, Katja C.; Dimopoulos, Meletios A.; Moreau, Philippe; Lacy, Martha Q.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Banos, Anne; Oriol, Albert; Alegre, Adrian; Chen, Christine; Cavo, Michele; Garderet, Laurent; Ivanova, Valentina; Martinez-Lopez, Joaquin; Knop, Stefan; Yu, Xin; Hong, Kevin; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Miguel, Jesus San

2016-01-01

Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 − < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 − < 60 mL/min (P<0.001) and 4.0 versus 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P<0.001). Median overall survival for pomalidomide + low-dose dexamethasone versus high-dose dexamethasone was 10.4 versus 4.9 months (P=0.030) and 15.5 versus 9.2 months (P=0.133), respectively. Improved renal function, defined as an increase in creatinine clearance from < 60 to ≥ 60 mL/min, was similar in pomalidomide + low-dose dexamethasone and high-dose dexamethasone patients (42% and 47%, respectively). Improvement in progression-free and overall survival in these patients was comparable with that in patients without renal impairment. There was no increase in discontinuations of therapy, dose modifications, and adverse events in patients with moderate renal impairment. Pomalidomide at a starting dose of 4 mg + low-dose dexamethasone is well tolerated in patients with refractory or relapsed and refractory multiple myeloma, and of comparable efficacy if moderate renal impairment is present. This trial was registered with clinicaltrials.gov identifier 01311687 and EudraCT identifier 2010-019820-30. PMID:27081177

Materials Sciences Research.

DTIC Science & Technology

1975-07-01

Physics of Refractory Materials (ERDA) ..... 160 J. Holder - Mechanical Properties of Solids (NSF) ...... 163 A. Granato - Anharmonic Effects in Solids...ERDA) ........ 166 6. Semiconductor Materials and Devices. N. Holonyak - Luinescence, Lasers, Carrier and Impurity Effects in Compound Semiconductors...1975. Dr. P. A. Egelstaff, University of Guelph, Ontario, Canada, "Three-Body Effects in Simple Fluids," April 9, 1975. Professor G. Leibfried, Oak

The enabling technology for recovery of valued components from minerals in the upper and Mid Amur region

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

Sorokin, A.P.; Rimkevich, V.S.; Dem'yanova, L.P.

2009-05-15

Based on the physico-technical operations involved in the mineral processing technologies, the optimal production conditions are found for refractory fiber materials, aluminium, silicium, their compounds and other valued components. Ecologically safe and efficient aggregate technologies are developed for recovery of valued components from nonmetallic minerals and anthracides (brown coals).

Land Application of Wastes: An Educational Program. Organic Matter - Module 17, Objectives, and Script.

ERIC Educational Resources Information Center

Clarkson, W. W.; And Others

This module sketches out the impact of sewage organic matter on soils. For convenience, that organic matter is separated into the readily decomposable compounds and the more resistant material (volatile suspended solids, refractory organics, and sludges). The fates of those organics are reviewed along with loading rates and recommended soil…

Intralesional Mycobacterium w Vaccine Versus Cryotherapy in Treatment of Refractory Extragenital Warts: A Randomized, Open-Label, Comparative Study.

PubMed

Dhakar, Ashok K; Dogra, Sunil; Vinay, Keshavamurthy; Sarangal, Rishu; Kanwar, Amrinder J; Singh, Mini P

2016-01-01

Initial reports of immunotherapy using intralesional Mycobacterium w (Mw) vaccine have documented its useful role in treatment of genital and extragenital warts. To compare the efficacy and safety of intralesional Mw vaccine versus cryotherapy in the treatment of refractory extragenital warts. This was a prospective, randomized, comparative study of 66 patients. The outcome was assessed in terms of complete clearance of warts and change in Dermatology Life Quality Index (DLQI) score. Complete clearance of treated warts was seen in 66.7% (20/30) and 65.5% (19/29) of patients in the Mw and cryotherapy groups, respectively (P = .769). Clearance of distant warts was significantly (P = .004) high in the Mw group. Improvement in DLQI was greater in the Mw group. Both treatment modalities were well tolerated, and no major side effects occurred. Mw vaccine and cryotherapy are equally efficacious in treatment of refractory extragenital warts. Mw vaccine has an added advantage of clearance of distant warts. © The Author(s) 2015.

Morphometric brain characterization of refractory obsessive-compulsive disorder: diffeomorphic anatomic registration using exponentiated Lie algebra.

PubMed

Tang, Wanjie; Li, Bin; Huang, Xiaoqi; Jiang, Xiaoyu; Li, Fei; Wang, Lijuan; Chen, Taolin; Wang, Jinhui; Gong, Qiyong; Yang, Yanchun

2013-10-01

Few studies have used neuroimaging to characterize treatment-refractory obsessive-compulsive disorder (OCD). This study sought to explore gray matter structure in patients with treatment-refractory OCD and compare it with that of healthy controls. A total of 18 subjects with treatment-refractory OCD and 26 healthy volunteers were analyzed by MRI using a 3.0-T scanner and voxel-based morphometry (VBM). Diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL) was used to identify structural changes in gray matter associated with treatment-refractory OCD. A partial correlation model was used to analyze whether morphometric changes were associated with Yale-Brown Obsessive-Compulsive Scale scores and illness duration. Gray matter volume did not differ significantly between the two groups. Treatment-refractory OCD patients showed significantly lower gray matter density than healthy subjects in the left posterior cingulate cortex (PCC) and mediodorsal thalamus (MD) and significantly higher gray matter density in the left dorsal striatum (putamen). These changes did not correlate with symptom severity or illness duration. Our findings provide new evidence of deficits in gray matter density in treatment-refractory OCD patients. These patients may show characteristic density abnormalities in the left PCC, MD and dorsal striatum (putamen), which should be verified in longitudinal studies. © 2013. Published by Elsevier Inc. All rights reserved.

Randomised controlled trial of brief intervention with biofeedback and hypnotherapy in patients with refractory irritable bowel syndrome.

PubMed

Dobbin, A; Dobbin, J; Ross, S C; Graham, C; Ford, M J

2013-01-01

Irritable bowel syndrome (IBS) is a common disorder associated with profoundly impaired quality of life and emotional distress. The management of refractory IBS symptoms remains challenging and non-pharmacological therapeutic approaches have been shown to be effective. We compared brief interventions with biofeedback and hypnotherapy in women referred by their GP with refractory IBS symptoms. Patients were randomised to one of two treatment groups, biofeedback or hypnotherapy, delivered as three one-hour sessions over 12 weeks. Symptom assessments were undertaken using validated, self-administered questionnaires. Two of the 128 consecutive IBS patients suitable for the study declined to consider nonpharmacological therapy and 29 patients did not attend beyond the first session. Of the 97 patients randomised into the study, 21 failed to attend the therapy session; 15 of 76 patients who attended for therapy dropped out before week 12 post-therapy. The mean (SD) change in IBS symptom severity score 12 weeks post-treatment in the biofeedback group was -116.8 (99.3) and in the hypnotherapy group -58.0 (101.1), a statistically significant difference between groups (difference=-58.8, 95% confidence interval [CI] for difference [-111.6, -6.1], p=0.029). In 61 patients with refractory IBS, biofeedback and hypnotherapy were equally effective at improving IBS symptom severity scores, total non-gastrointestinal symptom scores and anxiety and depression ratings during 24 weeks follow-up. Biofeedback may prove to be the more cost-effective option as it requires less expertise.

Shall we stay, or shall we switch? Continued anti-VEGF therapy versus early switch to dexamethasone implant in refractory diabetic macular edema.

PubMed

Busch, Catharina; Zur, Dinah; Fraser-Bell, Samantha; Laíns, Inês; Santos, Ana Rita; Lupidi, Marco; Cagini, Carlo; Gabrielle, Pierre-Henry; Couturier, Aude; Mané-Tauty, Valérie; Giancipoli, Ermete; Ricci, Giuseppe D'Amico; Cebeci, Zafer; Rodríguez-Valdés, Patricio J; Chaikitmongkol, Voraporn; Amphornphruet, Atchara; Hindi, Isaac; Agrawal, Kushal; Chhablani, Jay; Loewenstein, Anat; Iglicki, Matias; Rehak, Matus

2018-05-05

To compare functional and anatomical outcomes of continued anti-vascular endothelial growth factor (VEGF) therapy versus dexamethasone (DEX) implant in eyes with refractory diabetic macular edema (DME) after three initial anti-VEGF injections in a real-world setting. To be included in this retrospective multicenter, case-control study, eyes were required: (1) to present with early refractory DME, as defined by visual acuity (VA) gain ≤ 5 letters or reduction in central subfield thickness (CST) ≤ 20%, after a loading phase of anti-VEGF therapy (three monthly injections) and (2) to treat further with (a) anti-VEGF therapy or (b) DEX implant. Main outcome measures were change in visual acuity (VA) and central subfield thickness (CST) at 12 months. Due to imbalanced baseline characteristics, a matched anti-VEGF group was formed by only keeping eyes with similar baseline characteristics as those in the DEX group. A total of 110 eyes from 105 patients were included (anti-VEGF group: 72 eyes, DEX group: 38 eyes). Mean change in VA at 12 months was - 0.4 ± 10.8 letters (anti-VEGF group), and + 6.1 ± 10.6 letters (DEX group) (P = 0.004). Over the same period, mean change in CST was + 18.3 ± 145.9 µm (anti-VEGF group) and - 92.8 ± 173.6 µm (DEX group) (P < 0.001). Eyes in the DEX group were more likely to gain ≥ 10 letters (OR 3.71, 95% CI 1.19-11.61, P = 0.024) at month 12. In a real-world setting, eyes with DME considered refractory to anti-VEGF therapy after three monthly injections which were switched to DEX implant and had better visual and anatomical outcomes at 12 months than those that continued treatment with anti-VEGF therapy.

Defining refractory migraine: results of the RHSIS Survey of American Headache Society members.

PubMed

Schulman, Elliott A; Peterlin, B Lee; Lake, Alvin E; Lipton, Richard B; Hanlon, Alexandra; Siegel, Sherry; Levin, Morris; Goadsby, Peter J; Markley, Herbert G

2009-04-01

To gauge consensus regarding a proposed definition for refractory migraine proposed by Refractory Headache Special Interest Section, and where its use would be most appropriate. Headache experts have long recognized that a subgroup of headache sufferers remains refractory to treatment. Although different groups have proposed criteria to define refractory migraine, the definition remains controversial. The Refractory Headache Special Interest Section of the American Headache Society developed a definition through a consensus process, assisted by a literature review and initial membership survey. A 12-item questionnaire was distributed at the American Headache Society meeting in 2007 during a platform session and at the Refractory Headache Special Interest Section symposium. The same questionnaire was subsequently sent to all American Headache Society members via e-mail. A total of 151 responses from AHS members form the basis of this report. The survey instrument was designed using Survey Monkey. Frequencies and percentages of the survey were used to describe survey responses. American Headache Society members agreed that a definition for refractory migraine is needed (91%) that it should be added to the International Classification of Headache Disorders-2 (86%), and that refractory forms of non-migraine headache disorders should be defined (87%). Responders believed a refractory migraine definition would be of greatest value in selecting patients for clinical drug trials. The current refractory migraine definition requires a diagnosis of migraine, interference with function or quality of life despite modification of lifestyle factors, and adequate trials of acute and preventive medicines with established efficacy. The proposed criteria for the refractory migraine definition require failing 2 preventive medications to meet the threshold for failure. Although 42% of respondents agreed with the working definition of refractory migraine, 43% favored increasing the number to 3 (50%) or 4 (26%) preventive treatment failures. When respondents were asked if they felt that the proposed definition was appropriate to select patients for invasive procedures (patent foramen ovale repair or stimulators) only 44% agreed. There is a consensus for a need for a definition for refractory migraine and that it should be added to the International Classification of Headache Disorder-2. There was also general agreement by the responders that refractory forms of non-migraine headache disorders should be defined.

COMPUTING MEDIUM USING THRESHOLD ELEMENTS WITH COMBINED FUNCTIONS,

DTIC Science & Technology

by grouping a number of elements to perform the desired functions. In the pulsed threshold system, a refractory period exists when the elements do not...disjunction, storage, and interaction. The level threshold elements, on the other hand do not have a refractory property but nevertheless they are able to perform signal branching, NOR operation, negation, and storage. (Author)

Rare-earth metals in nickel aluminide-based alloys: III. Structure and properties of multicomponent Ni3Al-based alloys

NASA Astrophysics Data System (ADS)

Bazyleva, O. A.; Povarova, K. B.; Kazanskaya, N. K.; Drozdov, A. A.

2009-04-01

The possibility of increasing the life of heterophase cast light Ni3Al-based superalloys at temperatures higher than 0.8 T m of Ni3Al is studied when their directional structure is additionally stabilized by nanoprecipitates, which form upon additional alloying of these alloys by refractory and active metals, and using special methods for preparing and melting of an alloy charge. The effect of the method of introducing the main components and refractory reaction-active and surface-active alloying elements into Ni3Al-based cast superalloys, which are thermally stable natural composite materials of the eutectic type, on the structure-phase state and the life of these alloys is studied. When these alloys are melted, it is necessary to perform a set of measures to form particles of refractory oxide cores covered with the β-NiAl phase and, then, γ'prim-Ni3Al phase precipitates during solidification. The latter phase forms the outer shell of grain nuclei, which provides high thermal stability and hot strength of an intermetallic compound-based alloy. As a result, a modified structure that is stabilized by the nanoprecipitates of nickel and aluminum lanthanides and the nanoprecipitates of phases containing refractory metals is formed. This structure enhances the life of the alloy at 1000 °C by a factor of 1.8-2.5.

[Effect analysis on Deanxit combined with Shuganjieyu capsule in the treatment of refractory gastroesophageal reflux disease].

PubMed

Yang, X Y; Guo, C Y; Zhang, X; Zhong, Y Q; Tian, C

2017-11-28

Objective: To investigate the curative effect of Deanxit combined with Shuganjieyu capsule on the treatment of refractory gastroesophageal reflux disease. Methods: A total of 125 patients with refractory gastroesophageal reflux disease who had failed in standard lansolazole capsule treatment in the Department of Gastroenterology, First People's Hospital of Neijiang were selected. According to the symptom scores and mood scores of gastroesophageal reflux disease, patients were randomly and double-blindly divided into five groups. Group A(Lansoprazole Capsules + Mosapride Citrate + Deanxit), B(Lansoprazole Capsules + Mosapride Citrate + Shuganjieyu capsule), C(Lansoprazole Capsules + Mosapride Citrate+ Deanxit + Shuganjieyu capsule) and D(Deanxit) groups are study groups, the other was control group (Lansoprazole Capsules + Mosapride Citrate). The scores of symptoms and mood were compared after 4 weeks and 8 weeks of treatment. Results: The clinical symptoms score, HAMA and HAMD scores were significantly lower in the all study groups in comparison to the control group after 4 weeks and 8 weeks therapy. The clinical symptoms score, HAMA and HAMD scores in group C were significantly lower than those in group A and B ( P <0.05), while the difference between group A and B was not statistically significant( P >0.05). The HAMA and HAMD scores of group D were significantly higher than those of group A, B, C and control group, and the differences were statistically significant ( P <0.05). The total effective rate of study groups were significantly higher than those of the control group, and the difference was statistically significant ( P <0.05). The total effective rate of group C was significantly higher than that of group A and B (χ(2)=6.47, P <0.05). The total effective rate of group A at the end of the 8th week was significantly higher than that of group B (χ(2)=6.52, P <0.05). The total effective rate of group D at the end of the 4th and 8th week was significantly lower than those of the group A, B, C and control group, the difference was statistically significant (χ(2)=5.85, P <0.05). Conclusions: Deanxit combined with Shuganjieyu capsule is significantly effective in treatment of refractory gastroesophageal reflux disease, which can effectively improve the total treatment efficiency, reduce the symptom scores and mood scores of gastroesophageal reflux disease patients.

Prolotherapy for Refractory Rotator Cuff Disease: Retrospective Case-Control Study of 1-Year Follow-Up.

PubMed

Lee, Doo-Hyung; Kwack, Kyu-Sung; Rah, Ueon Woo; Yoon, Seung-Hyun

2015-11-01

To determine the efficacy of prolotherapy for refractory rotator cuff disease. Retrospective case-control study. University-affiliated tertiary care hospital. Patients with nontraumatic refractory rotator cuff disease (N=151) who were unresponsive to 3 months of aggressive conservative treatment. Of the patients, 63 received prolotherapies with 16.5% dextrose 10-ml solution (treatment group), and 63 continued conservative treatment (control group). Not applicable. Visual analog scale (VAS) score of the average shoulder pain level for the past 1 week, Shoulder Pain and Disability Index (SPADI) score, isometric strength of the shoulder abductor, active range of motion (AROM) of the shoulder, maximal tear size on ultrasonography, and number of analgesic ingestions per day. Over 1-year follow-up, 57 patients in the treatment group and 53 in the control group were analyzed. There was no significant difference between the 2 groups in age, sex, shoulder dominance, duration of symptoms, and ultrasonographic findings at pretreatment. The average number of injections in the treatment group is 4.8±1.3. Compared with the control group, VAS score, SPADI score, isometric strength of shoulder abductor, and shoulder AROM of flexion, abduction, and external rotation showed significant improvement in the treatment group. There were no adverse events. To our knowledge, this is the first study to assess the efficacy of prolotherapy in rotator cuff disease. Prolotherapy showed improvement in pain, disability, isometric strength, and shoulder AROM in patients with refractory chronic rotator cuff disease. The results suggest positive outcomes, but one should still take caution in directly interpreting it as an effective treatment option, considering the limitations of this nonrandomized retrospective study. To show the efficacy of prolotherapy, further studies on prospective randomized controlled trials will be required. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Asia-Pacific consensus on the management of gastro-oesophageal reflux disease: an update focusing on refractory reflux disease and Barrett's oesophagus.

PubMed

Fock, Kwong Ming; Talley, Nicholas; Goh, Khean Lee; Sugano, Kentaro; Katelaris, Peter; Holtmann, Gerald; Pandolfino, John E; Sharma, Prateek; Ang, Tiing Leong; Hongo, Michio; Wu, Justin; Chen, Minhu; Choi, Myung-Gyu; Law, Ngai Moh; Sheu, Bor-Shyang; Zhang, Jun; Ho, Khek Yu; Sollano, Jose; Rani, Abdul Aziz; Kositchaiwat, Chomsri; Bhatia, Shobna

2016-09-01

Since the publication of the Asia-Pacific consensus on gastro-oesophageal reflux disease in 2008, there has been further scientific advancement in this field. This updated consensus focuses on proton pump inhibitor-refractory reflux disease and Barrett's oesophagus. A steering committee identified three areas to address: (1) burden of disease and diagnosis of reflux disease; (2) proton pump inhibitor-refractory reflux disease; (3) Barrett's oesophagus. Three working groups formulated draft statements with supporting evidence. Discussions were done via email before a final face-to-face discussion. We used a Delphi consensus process, with a 70% agreement threshold, using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to categorise the quality of evidence and strength of recommendations. A total of 32 statements were proposed and 31 were accepted by consensus. A rise in the prevalence rates of gastro-oesophageal reflux disease in Asia was noted, with the majority being non-erosive reflux disease. Overweight and obesity contributed to the rise. Proton pump inhibitor-refractory reflux disease was recognised to be common. A distinction was made between refractory symptoms and refractory reflux disease, with clarification of the roles of endoscopy and functional testing summarised in two algorithms. The definition of Barrett's oesophagus was revised such that a minimum length of 1 cm was required and the presence of intestinal metaplasia no longer necessary. We recommended the use of standardised endoscopic reporting and advocated endoscopic therapy for confirmed dysplasia and early cancer. These guidelines standardise the management of patients with refractory gastro-oesophageal reflux disease and Barrett's oesophagus in the Asia-Pacific region. 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/

NASA research on refractory compounds.

NASA Technical Reports Server (NTRS)

Gangler, J. J.

1971-01-01

The behavior and properties of the refractory carbides, nitrides, and borides are being investigated by NASA as part of its research aimed at developing superior heat resistant materials for aerospace applications. Studies of the zirconium-carbon-oxygen system show that zirconium oxycarbides of different compositions and lattice parameters can be formed between 1500 C and 1900 C and are stable below 1500 C. More applied studies show that hot working generally improves the microstructure and therefore the strength of TiC and NbC. Sintering studies on UN indicate that very high densities can be achieved. Hot pressing of cermets of HfN and HfC produces good mechanical properties for high temperature bearing applications. Attempts to improve the impact resistance of boride composites by the addition of a nickel or carbon yarn were not overly successful.

Method for producing refractory nitrides

DOEpatents

Quinby, Thomas C.

1989-01-24

A process for making fine, uniform metal nitride powders that can be hot pressed or sintered. A metal salt is placed in a solvent with Melamine and warmed until a metal-Melamine compound forms. The solution is cooled and the metal-Melamine precipitate is calcined at a temperature below 700.degree. C. to form the metal nitrides and to avoid formation of the metal oxide.

Molybdenum disilicide alloy matrix composite

DOEpatents

Petrovic, John J.; Honnell, Richard E.; Gibbs, W. Scott

1990-01-01

Compositions of matter consisting of matrix matrials having silicon carbide dispersed throughout them and methods of making the compositions. A matrix material is an alloy of an intermetallic compound, molybdenum disilicide, and at least one secondary component which is a refractory silicide. The silicon carbide dispersant may be in the form of VLS whiskers, VS whiskers, or submicron powder or a mixture of these forms.

Molybdenum disilicide alloy matrix composite

DOEpatents

Petrovic, John J.; Honnell, Richard E.; Gibbs, W. Scott

1991-01-01

Compositions of matter consisting of matrix materials having silicon carbide dispersed throughout them and methods of making the compositions. A matrix material is an alloy of an intermetallic compound, molybdenum disilicide, and at least one secondary component which is a refractory silicide. The silicon carbide dispersant may be in the form of VLS whiskers, VS whiskers, or submicron powder or a mixture of these forms.

Studies of Silicon Refractory Metal Interfaces: Photoemission Study of Interface Formation and Compound Nucleation.

DTIC Science & Technology

1983-09-08

1982). 4. A. Hiraki , M.-A. Nicolet, and J.W. Mayer, Appl. Phys. Lett. 18, 178 (1971); A. Hiraki , K. Shuto, S. Kim, W. Kammura, and M. twami, ibid 31...Vac. Sci. Technol. 17, 930 (1980) and references therein. 13 T. Narusera, K. Kinoehica, W. 1. Gibson, and A. Hiraki , J. Vac. Sci. Technol. L$, 272

Immunomodulatory therapy in refractory/recurrent ovarian cancer.

PubMed

Chen, Chao-Yu; Lai, Chyong-Huey; Yang, Lan-Yan; Tang, Yun-Hsin; Chou, Hung-Hsueh; Chang, Chee-Jen; Lin, Cheng-Tao

2015-04-01

To investigate the efficacy and toxicity of immunomodulatory therapy (IMT) alone or as an add-on to palliative/salvage chemotherapy in patients with refractory/recurrent epithelial ovarian cancer (EOC). We retrospectively analyzed the efficacy and toxicity of IMT in 15 patients with refractory/recurrent EOC who had previously received multiple chemotherapy regimens. The median age of the patients was 56 years (range, 41-75 years). Three patients were platinum-sensitive, two were platinum-resistant, and the remaining 10 patients were refractory to platinum-based front-line chemotherapy. IMT consisted of picibanil (OK-432) on Day 1, interleukin-2 and/or interferon-α on Day 2 administered by subcutaneous injection (every week or 2-weekly). Five patients never received metronomic oral cyclophosphamide. After IMT, three patients achieved partial remission (PR, lasting for 11 months, ≥ 12 months, and 16 months), and six patients had stable disease (SD). The disease stabilizing rate (PR+SD) was 60% (3/3 in platinum-sensitive and 6/12 in platinum-resistant/refractory patients). The absolute lymphocyte count (ALC) at 1 month after IMT was significantly higher in the PR+SD group (median 1242.0/μL) than in the progression group (median 325.0/μL) (p = 0.012). No ≥ Grade 3 toxicities were observed. The median post-IMT survival time was 12 months (range, 2-39 months). IMT alone or add-on to palliative/salvage chemotherapy for refractory/recurrent EOC achieves a substantial disease stabilizing rate without severe toxicity, which might be a potential option in selected patients. The ALC 1 month after IMT could be an early indicator to disease stabilization. Copyright © 2015. Published by Elsevier B.V.

Management of Psoriasis with a XemaTop Topical Compounded Formula: A Case Report.

PubMed

Jones, Nat; Carvalho, Maria; Branvold-Herr, Andrea

2017-01-01

Skin conditions such as psoriasis and eczema negatively impact the patient's quality of life; the primary goal of topical treatments is to minimize the disease-specific symptoms. This case report discusses the management of two refractory psoriasis skin lesions in an adult male using a topical compounded formula. The psoriasis symptoms were assessed quantitatively using two validated research instruments, the Psoriasis Symptom Inventory, and an adapted Numeric Rating Scale. A qualitative assessment was also performed by evaluating the digital photographs taken by the patient during the course of treatment. The compounded formula containing zinc pyrithione, clobetasol propionate, and cyanocobalamin in the Professional Compounding Centers of America's proprietary base PCCA XemaTop, applied topically for three weeks, significantly reduced the patient's self-reported psoriasis symptoms and improved his overall condition by 81.2%. This successful case report is important evidence for healthcare professionals when considering new, innovative topical compounded formulas for managing skin conditions such as psoriasis and eczema. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Alloy design for intrinsically ductile refractory high-entropy alloys

NASA Astrophysics Data System (ADS)

Sheikh, Saad; Shafeie, Samrand; Hu, Qiang; Ahlström, Johan; Persson, Christer; Veselý, Jaroslav; Zýka, Jiří; Klement, Uta; Guo, Sheng

2016-10-01

Refractory high-entropy alloys (RHEAs), comprising group IV (Ti, Zr, Hf), V (V, Nb, Ta), and VI (Cr, Mo, W) refractory elements, can be potentially new generation high-temperature materials. However, most existing RHEAs lack room-temperature ductility, similar to conventional refractory metals and alloys. Here, we propose an alloy design strategy to intrinsically ductilize RHEAs based on the electron theory and more specifically to decrease the number of valence electrons through controlled alloying. A new ductile RHEA, Hf0.5Nb0.5Ta0.5Ti1.5Zr, was developed as a proof of concept, with a fracture stress of close to 1 GPa and an elongation of near 20%. The findings here will shed light on the development of ductile RHEAs for ultrahigh-temperature applications in aerospace and power-generation industries.

Cytokine analysis in lesions refractory to endodontic treatment.

PubMed

Henriques, Luiz Carlos Feitosa; de Brito, Luciana Carla Neves; Tavares, Warley Luciano Fonseca; Vieira, Leda Quércia; Ribeiro Sobrinho, Antônio Paulino

2011-12-01

Failure in endodontic treatment is often caused by the persistence of microorganisms in the root canal after therapy. When treatment fails, an immune response develops that is characterized by an extensive network of immunologic mechanisms that lead to the production of cytokines and chemokines. The objective of this study was to determine the relative messenger RNA (mRNA) expression of IFN-γ, TNF-α, IL-1β, IL-17A, IL-10, and MCP-1 in periapical dental lesions refractory to treatment. Clinical samples were taken from teeth presenting periapical lesions refractory to endodontic treatment (the experimental group) or from healthy teeth with pulp vitality (the control group). Three paper points passing through the root apex (2 mm) were used to collect the samples. The total RNA was extracted from each sample, complementary DNA was synthesized, and quantitative polymerase chain reaction analysis was performed. The Mann-Whitney U test was used to determine the statistical significance of our findings (P < .05). Significant differences in the levels of IFN-γ, TNF-α, IL-17A, and MCP-1 mRNA expression were observed in cases refractory to endodontic treatment as compared with the control group. The expression of IL-1β mRNA was not significantly different between the groups. The expression of IL-10 mRNA was insignificant in both the experimental and control groups. A significantly increased expression of TNF-α, IFN-γ, IL-17A, and MCP-1 mRNA was observed in the periapical immune response in cases of endodontic failure. These results suggest that a proinflammatory cytokine profile predominates in these types of dental lesions. Copyright © 2011 American Association of Endodontists. All rights reserved.

Clinical assessment of diode laser-assisted endoscopic intrasphenoidal vidian neurectomy in the treatment of refractory rhinitis.

PubMed

Lai, Wen-Sen; Cheng, Sheng-Yao; Lin, Yuan-Yung; Yang, Pei-Lin; Lin, Hung-Che; Cheng, Li-Hsiang; Yang, Jinn-Moon; Lee, Jih-Chin

2017-12-01

For chronic rhinitis that is refractory to medical therapy, surgical intervention such as endoscopic vidian neurectomy (VN) can be used to control the intractable symptoms. Lasers can contribute to minimizing the invasiveness of ENT surgery. The aim of this retrospective study is to compare in patients who underwent diode laser-assisted versus traditional VN in terms of operative time, surgical field, quality of life, and postoperative complications. All patients had refractory rhinitis with a poor treatment response to a 6-month trial of corticosteroid nasal sprays and underwent endoscopic VN between November 2006 and September 2015. They were non-randomly allocated into either a cold instrument group or a diode laser-assisted group. Vidian nerve was excised with a 940-nm continuous wave diode laser through a 600-μm silica optical fiber, utilizing a contact mode with the power set at 5 W. A visual analog scale (VAS) was used to grade the severity of the rhinitis symptoms for quality of life assessment before the surgery and 6 months after. Of the 118 patients enrolled in the study, 75 patients underwent cold instrument VN and 43 patients underwent diode laser-assisted VN. Patients in the laser-assisted group had a significantly lower surgical field score and a lower postoperative bleeding rate than those in the cold instrument group. Changes in the VAS were significant in preoperative and postoperative nasal symptoms in each group. The application of diode lasers for vidian nerve transection showed a better surgical field and a lower incidence of postoperative hemorrhage. Recent advancements in laser application and endoscopic technique has made VN safer and more effective. We recommend this surgical approach as a reliable and effective treatment for patients with refractory rhinitis.

Comparison of Efficacy Between Endoscopic Cyclophotocoagulation and Alternative Surgeries in Refractory Glaucoma

PubMed Central

Yang, Yangfan; Zhong, Jing; Dun, Zhongjun; Liu, Xiao-an; Yu, Minbin

2015-01-01

Abstract Refractory glaucoma refers to uncontrolled intraocular pressure (IOP) despite anti-glaucoma medication and surgical treatment, which remains a challenge to be treated. The objective of this study is to evaluate and statistically compare the clinical efficacy between endoscopic cyclophotocoagulation (ECP) and alternative surgical techniques in the treatment of refractory glaucoma in this article, as a meta-analysis. Data sources are China Biomedical Database (Sinomed, online version), China National Knowledge Infrastructure (CNKI), Cqvip, Wanfang database, and PubMed. The randomized controlled trial (RCT) and case–control study literatures evaluating the clinical efficacy between ECP and other surgical techniques were searched electronically from public databases. The methodology quality of the retrieved articles was evaluated according to the RCT or case–control study criteria. The success rate of treatment, intraocular pressure (IOP) and visual acuity were statistically compared. RevMan 5.3 software was used for the meta-analysis. In total, 6 relevant control studies were selected in this study with a total sampling of 429 cases (429 eyes), including 204 eyes in the ECP group and 225 in the non-ECP group. Meta-analysis demonstrated that the clinical efficacy did not significantly differ between 2 groups (P > 0.05). Postoperative IOP was dramatically reduced in both groups. However, it was difficult to evaluate the combined influence of ECP and non-ECP therapies upon IOP reduction. In conclusion, ECP and non-ECP treatment yielded almost equivalent clinical efficacy in treating refractory glaucoma. The IOP-lowering degree, safety, and incidence of complications remain to be further elucidated by RCTs with a larger sample size. PMID:26426659

Atypical auditory refractory periods in children from lower socio-economic status backgrounds: ERP evidence for a role of selective attention.

PubMed

Stevens, Courtney; Paulsen, David; Yasen, Alia; Neville, Helen

2015-02-01

Previous neuroimaging studies indicate that lower socio-economic status (SES) is associated with reduced effects of selective attention on auditory processing. Here, we investigated whether lower SES is also associated with differences in a stimulus-driven aspect of auditory processing: the neural refractory period, or reduced amplitude response at faster rates of stimulus presentation. Thirty-two children aged 3 to 8 years participated, and were divided into two SES groups based on maternal education. Event-related brain potentials were recorded to probe stimuli presented at interstimulus intervals (ISIs) of 200, 500, or 1000 ms. These probes were superimposed on story narratives when attended and ignored, permitting a simultaneous experimental manipulation of selective attention. Results indicated that group differences in refractory periods differed as a function of attention condition. Children from higher SES backgrounds showed full neural recovery by 500 ms for attended stimuli, but required at least 1000 ms for unattended stimuli. In contrast, children from lower SES backgrounds showed similar refractory effects to attended and unattended stimuli, with full neural recovery by 500 ms. Thus, in higher SES children only, one functional consequence of selective attention is attenuation of the response to unattended stimuli, particularly at rapid ISIs, altering basic properties of the auditory refractory period. Together, these data indicate that differences in selective attention impact basic aspects of auditory processing in children from lower SES backgrounds. Copyright © 2013 Elsevier B.V. All rights reserved.

[Site of prelingual cochlear stimulation and its effect on electrically evoked compound action potentials and refractory using the Nucleus 24 standard].

PubMed

Ma, R Y; Li, W; Jiang, X J

2016-12-01

Objective: To investigate the correlation between the site of prelingual cochlear stimulation and its effect on electrically evoked compound action potentials. Method: Recordings of auditory nerve responses were conducted in 32 prelingual subjects to demonstrate the feasibility of ECAP recordings using the nerve response telemetry(NRT) feature of the Nucleus CI24R(CA) system software. These recordings were then analyzed based on the site of cochlear stimulation defined as basal, middle and apical to determine if the amplitude, threshold and slope of the amplitude growth function and the refractory time differs depending on the region of stimulation. Result: Findings of our prelingual children showed significant differences in the ECAP recordings depending on the stimulation site. Comparing the apical with the basal region, on average higher amplitudes, lower thresholds and steeper slopes of the amplitude growth function hadbeen observed. The refractory time showed an overall dependence on cochlear region; however post-hoc tests showed no significant effect between individual regions. Conclusion: Obtaining ECAP recordings is also possible in the most apical region of the cochlea. However, differences can be observed depending on the region of the cochlea stimulated. Specifically, significant higher ECAP amplitude, lower thresholds and steeper amplitude growth function slopes have been observed in the apical region. These differences between prelingual children and adults could be explained by the location of the stimulating electrode with respect to the neural tissue in the cochlea, a higher density, or an increased neural survival rate of neural tissue in the apex. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Clinical characteristics and prognostic factors of prostate cancer with liver metastases.

PubMed

Wang, HaiTao; Li, BaoGuo; Zhang, PengYu; Yao, YanHong; Chang, JiWu

2014-01-01

Liver metastasis from prostate cancer is uncommon and remains poorly understood. We computer searched the clinical records of all our patients registered into a database to identify patients that presented or developed liver metastases. A total of 27 prostate cancer patients with ultrasound or CT/MR imaging evidence of liver metastases were included in our analysis. The liver metastasis rate from metastatic prostate cancer was 4.29%. Eight (29.63%) patients had previously untreated, hormone-naive prostate cancer (synchronous liver metastases at diagnosis of prostate cancer), whereas 19 (70.37%) patients had already been diagnosed as having hormone-refractory prostate cancer. In the hormone-naive group, the median overall survival after liver metastases diagnosis was 38 months and half of the patients were still alive at the latest follow-up, whereas only 6 months in the hormone-refractory group (p = 0.003). High concentration of serum neuron-specific enolase and previous chemotherapy were associated with a significantly poor overall survival after liver metastases in the hormone-refractory group using Kaplan–Meier curves and logrank tests for univariate analysis.

Alternating Acetaminophen and Ibuprofen versus Monotherapies in Improvements of Distress and Reducing Refractory Fever in Febrile Children: A Randomized Controlled Trial.

PubMed

Luo, Shuanghong; Ran, Mengdong; Luo, Qiuhong; Shu, Min; Guo, Qin; Zhu, Yu; Xie, Xiaoping; Zhang, Chongfan; Wan, Chaomin

2017-10-01

No evidence can be found in the medical literature about the efficacy of alternating acetaminophen and ibuprofen treatment in children with refractory fever. Our objective was to assess the effect of alternating acetaminophen and ibuprofen therapy on distress and refractory fever compared with acetaminophen or ibuprofen as monotherapy in febrile children. A total of 474 febrile children with axillary temperature ≥38.5 °C and fever history ≤3 days in a tertiary hospital were randomly assigned to receive either (1) alternating acetaminophen and ibuprofen (acetaminophen 10 mg/kg per dose with shortest interval of 4 h and ibuprofen 10 mg/kg per dose with shortest interval of 6 h and the shortest interval between acetaminophen and ibuprofen ≥2 h; n = 158), (2) acetaminophen monotherapy (10 mg/kg per dose with shortest interval of 4 h; n = 158), or (3) ibuprofen monotherapy (10 mg/kg per dose with shortest interval of 6 h; n = 158). The mean Non-Communicating Children's Pain Checklist (NCCPC) score was measured every 4 h, and axillary temperatures were measured every 2 h. In total, 471 children were included in an intention-to-treat analysis. No significant clinical or statistical difference was found in mean NCCPC score or temperature during the 24-h treatment period in all febrile children across the three groups. Although the proportion of children with refractory fever for 4 h and 6 h was significantly lower in the alternating group than in the monotherapy groups (4 h: 11.54% vs. 26.58% vs. 21.66%, respectively [p = 0.003]; 6 h: 3.85% vs. 10.13% vs. 17.83%, respectively [p < 0.001]), the mean NCCPC score of children with refractory fever for 4 or 6 h was not lower than those in either of the monotherapy groups. The number of patients who developed persistent high body temperature was consistent across all study groups. Alternating acetaminophen and ibuprofen can reduce the proportion of children with refractory fever, but if one cycle of alternating therapy cannot reduce febrile distress as defined by NCCPC score, two or more cycles of alternating therapy may have minimal to no clinical efficacy in some cases. The trial was registered with the Chinese Clinical Trial Registry as ChiCTR-TRC-13003440 and the WHO Registry Network as U1111-1146-6714.

Comparison of male reproductive success in malaria-refractory and susceptible strains of Anopheles gambiae

PubMed Central

Voordouw, Maarten J; Koella, Jacob C; Hurd, Hilary

2008-01-01

Background In female mosquitoes that transmit malaria, the benefits of being refractory to the Plasmodium parasite are balanced by the immunity costs in the absence of infection. Male mosquitoes, however, gain no advantage from being refractory to blood-transmitted parasites, so that any costs associated with an enhanced immune system in the males limit the evolution of female refractoriness and has practical implications for the release of transgenic males. Methods Aspects of the male cost of carrying Plasmodium-refractory genes were estimated by comparing the males' immune response and reproductive success among strains of Anopheles gambiae that had been selected for refractoriness or extreme susceptibility to the rodent malaria parasite, Plasmodium yoelii nigeriensis. The refractory males had a stronger melanization response than males from the susceptible line. Four traits were used as correlates of a male's reproductive success: the proportion of females that were inseminated by a fixed number of males in a cage within a fixed time frame, the proportion of females with motile sperm in their spermathecae, the proportion of ovipositing females, and the mean number of eggs per batch. Results Although there were significant differences among groups of males in sperm motility and oviposition success, these differences in male reproductive success were not associated with the refractory or susceptible male genotypes. Contrary to expectation, females mated to early emerging refractory males laid significantly more eggs per batch than females mated to later emerging susceptible males. Sperm motility and oviposition success were strongly correlated suggesting that variation in sperm motility influences female oviposition and ultimately male reproductive success. Conclusion An increased melanization response in male A. gambiae does not diminish male reproductive success under the experimental protocol used in this study. That refractory males induced ovipositing females to lay more eggs than susceptible males is an interesting result for any strategy considering the release of transgenic males. That sperm motility influences female oviposition is also important for the release of transgenic males. PMID:18534029

High temperature regenerative H.sub.2 S sorbents

NASA Technical Reports Server (NTRS)

Flytani-Stephanopoulos, Maria (Inventor); Gavalas, George R. (Inventor); Tamhankar, Satish S. (Inventor)

1988-01-01

Efficient, regenerable sorbents for removal of H.sub.2 S from high temperature gas streams comprise porous, high surface area particles. A first class of sorbents comprise a thin film of binary oxides that form a eutectic at the temperature of the gas stream coated onto a porous, high surface area refractory support. The binary oxides are a mixture of a Group VB or VIB metal oxide with a Group IB, IIB or VIII metal oxide such as a film of V-Zn-O, V-Cu-O, Cu-Mo-O, Zn-Mo-O or Fe-Mo-O coated on an alumina support. A second class of sorbents consist of particles of unsupported mixed oxides in the form of highly dispersed solid solutions of solid compounds characterized by small crystallite size, high porosity and relatively high surface area. The mixed oxide sorbents contain one Group IB, IIB or VIIB metal oxide such as copper, zinc or manganese and one or more oxides of Groups IIIA, VIB or VII such as aluminum, iron or molybdenum. The presence of iron or aluminum maintains the Group IB, IIB or VIIB metal in its oxidized state. Presence of molybdenum results in eutectic formation at sulfidation temperature and improves the efficiency of the sorbent.

Patient with Gorlin syndrome and metastatic basal cell carcinoma refractory to smoothened inhibitors.

PubMed

Zhu, Gefei A; Li, Angela S; Chang, Anne Lynn S

2014-08-01

Basal cell carcinomas (BCCs) in patients with Gorlin syndrome have been reported to be extremely sensitive to Smoothened (SMO) inhibitors, a novel targeted therapy against the Hedgehog pathway, because of characteristic mutations in these patients. A few cases of disease refractory to oral therapy with SMO inhibitors have been reported in patients with Gorlin syndrome and nonmetastatic BCCs, but refractory disease in distantly metastatic tumors has not been documented in this high-risk group. A man with Gorlin syndrome and innumerable cutaneous BCCs presented with biopsy-proven BCC in his lungs. After SMO inhibitor therapy, almost all of his cutaneous tumors shrank, but his lung metastases did not. These lung metastases remained refractory to treatment despite institution of a second SMO inhibitor. We report a case of Gorlin syndrome in a patient with metastatic BCC refractory to SMO inhibitors. Furthermore, clinical responses in this patient's cutaneous tumors did not parallel the responses in the distant site. However, serial imaging after diagnosis of metastatic disease can be critical to monitor for response to therapy.

Increasing Ketamine Use for Refractory Status Epilepticus in US Pediatric Hospitals.

PubMed

Keros, Sotirios; Buraniqi, Ersida; Alex, Byron; Antonetty, Annalee; Fialho, Hugo; Hafeez, Baria; Jackson, Michele C; Jawahar, Rachel; Kjelleren, Stephanie; Stewart, Elizabeth; Morgan, Lindsey A; Wainwright, Mark S; Sogawa, Yoshimi; Patel, Anup D; Loddenkemper, Tobias; Grinspan, Zachary M

2017-06-01

Ketamine is an emerging therapy for pediatric refractory status epilepticus. The circumstances of its use, however, are understudied. The authors described pediatric refractory status epilepticus treated with ketamine from 2010 to 2014 at 45 centers using the Pediatric Hospital Inpatient System database. For comparison, they described children treated with pentobarbital. The authors estimated that 48 children received ketamine and pentobarbital for refractory status epilepticus, and 630 pentobarbital without ketamine. Those receiving only pentobarbital were median age 3 [interquartile range 0-10], and spent 30 [18-52] days in-hospital, including 17 [9-28] intensive care unit (ICU) days; 17% died. Median cost was $148 000 [81 000-241 000]. The pentobarbital-ketamine group was older (7 [2-11]) with longer hospital stays (51 [30-93]) and more ICU days (29 [20-56]); 29% died. Median cost was $298 000 [176 000-607 000]. For 71%, ketamine was given ≥1 day after pentobarbital. Ketamine cases per half-year increased from 2 to 9 ( P < .05). Ketamine is increasingly used for severe pediatric refractory status epilepticus, typically after pentobarbital. Research on its effectiveness is indicated.

Refractory and/or Relapsing Cryptococcosis Associated with Acquired Immune Deficiency Syndrome: Clinical Features, Genotype, and Virulence Factors of Cryptococcus spp. Isolates.

PubMed

Nascimento, Erika; Vitali, Lucia H; Tonani, Ludmilla; Kress, Marcia R Von Zeska; Takayanagui, Osvaldo M; Martinez, Roberto

2016-05-04

Refractory and relapsing crytocococcosis in acquired immune deficiency syndrome (AIDS) patients have a poor prognosis. The risk factors for this complicated infection course were evaluated by comparing refractory and/or relapsing cryptococcosis in human immunodeficiency virus-coinfected patients (cohort 1) with another group of AIDS patients who adequately responded to antifungals (cohort 2). Except for one isolate of Cryptococcus gattii from a cohort 2 case, all other isolates were identified as Cryptococcus neoformans var. grubii, sex type α, genotype VNI, including Cryptococcus reisolated from the relapse or in the refractory state. No differences were observed with respect to Cryptococcus capsule size and in the melanin and phospholipase production. The cohort 1 patients presented higher prevalence of cryptococcemia, cerebral dissemination, chronic liver disease, and leucopenia, and have increased death rate. Apparently, the refractory and/or relapsing cryptococcosis in the AIDS patients were more related to the host and the extent of the infection than to the fungal characteristics. © The American Society of Tropical Medicine and Hygiene.

Investigation of magnetic resonance imaging texture analysis as an aid tool for characterization of refractory epilepsies.

PubMed

Baldissin, Maurício Martins; Souza, Edna Marina de

2013-12-01

Refractory epilepsies are syndromes for which therapies that employ two or more antiepileptic drugs, separately or in association, do not result in control of crisis. Patients may present focal cortical dysplasia or diffuse dysplasia and/or hippocampal atrophic alterations that may not be detectable by a simple visual analysis in magnetic resonance imaging. The aim of this study was to evaluate MRI texture in regions of interest located in the hippocampi, limbic association cortex and prefrontal cortex of 20 patients with refractory epilepsy and to compare them with the same areas in 20 healthy individuals, in order to find out if the texture parameters could be related to the presence of the disease. Of the 11 texture parameters calculated, three indicated the existence of statistically significant differences between the studied groups. Such findings suggest the possibility of this technique contributing to studies of refractory epilepsies.

Ionic liquid-functionalized mesoporous sorbents and their use in the capture of polluting gases

DOEpatents

Lee, Jong Suk; Koros, William J.; Bhuwania, Nitesh; Hillesheim, Patrick C.; Dai, Sheng

2016-01-12

A composite structure for capturing a gaseous electrophilic species, the composite structure comprising mesoporous refractory sorbent particles on which an ionic liquid is covalently attached, wherein said ionic liquid includes an accessible functional group that is capable of binding to said gaseous electrophilic species. In particular embodiments, the mesoporous sorbent particles are contained within refractory hollow fibers. Also described is a method for capturing a gaseous electrophilic species by use of the above-described composite structure, wherein the gaseous electrophilic species is contacted with the composite structure. In particular embodiments thereof, cooling water is passed through the refractory hollow fibers containing the IL-functionalized sorbent particles in order to facilitate capture of the gaseous electrophilic species, and then steam is passed through the refractory hollow fibers to facilitate release of the gaseous electrophilic species such that the composite structure can be re-used to capture additional gas.

The Research Laboratory of Electronics Progress Report Number 133, January 1-December 1990

DTIC Science & Technology

1990-12-31

4 6 Chapter 7 High-Frequency InAlAs/InGaAs Metal -Insulator-Doped Semiconductor...Epitaxy of Compound Semiconductors Chapter 7 High-Frequency InAlAs/InGaAs Metal -Insulator- Doped Semiconductor Field-Effect Transistors (MIDFETs) for...aligned silicided NMOS posed of refractory metals to allow a subsequentdevice fabrication. We have used cobalt deposi- high temperature anneal. This

Fabrication and surface characterization of composite refractory compounds suitable for thermionic converters

NASA Technical Reports Server (NTRS)

Davis, P. R.; Swanson, L. W.

1979-01-01

The techniques of fabricating and characterizing the surface properties of electrode materials were investigated. The basic surface properties of these materials were studied with respect to their utilization as thermionic energy converter electrodes. Emphasis was placed on those factors (e.g, cesium disorption kinetic and mechanisms of low work function production) which are of primary concern to thermionic converter performance.

Molybdenum disilicide alloy matrix composite

DOEpatents

Petrovic, J.J.; Honnell, R.E.; Gibbs, W.S.

1991-12-03

Compositions of matter consisting of matrix materials having silicon carbide dispersed throughout them and methods of making the compositions are disclosed. A matrix material is an alloy of an intermetallic compound, molybdenum disilicide, and at least one secondary component which is a refractory silicide. The silicon carbide dispersant may be in the form of VLS whiskers, VS whiskers, or submicron powder or a mixture of these forms. 3 figures.

Polyprenylated polycyclic acylphloroglucinol: Angiogenesis inhibitor from Garcinia multiflora.

PubMed

Cheng, Lin-Yang; Chen, Chun-Lin; Kuo, Yueh-Hsiung; Chang, Tsung-Hsien; Lin, I-Wei; Wang, Shih-Wei; Chung, Mei-Ing; Chen, Jih-Jung

2018-06-01

A new polyprenylated polycyclic acylphloroglucinol, garcimultiflorone K (1), has been isolated from the stems of Garcinia multiflora, together with two known compounds, garcimultiflorone A (2) and garcimultiflorone B (3). The structure of new compound 1 was determined through spectroscopic methods including 1D and 2D NMR and MS analyses. The anti-angiogenic and anti-cancer effects of compounds 1-3 were evaluated in human endothelial progenitor cells (EPCs) and cancer cells. Of these, garcimultiflorone K (1) displayed the most potent anti-angiogenic property by suppressing cell growth and tube formation of EPCs. Compound 1 also exhibited growth-inhibitory activities against human hepatocellular carcinoma cell line SK-Hep-1 and hormone refractory prostate cancer cell line PC-3 with GI 50 values of 4.3 ± 1.6 and 6.6 ± 0.4 μM, respectively. Copyright © 2018 Elsevier Ltd. All rights reserved.

NASA research on refractory compounds.

NASA Technical Reports Server (NTRS)

Gangler, J. J.

1971-01-01

The behavior and properties of the refractory carbides, nitrides, and borides are being investigated by NASA as part of its research aimed at developing superior heat resistant materials for aerospace applications. Fundamental studies on the electronic and defect structures of the carbides indicate that there is promise for improving the strength and ductility of these materials. Studies of the zirconium-carbon-oxygen system show that zirconium oxycarbides of different compositions and lattice parameters can be formed between 1500 and 1900 C and are stable below 1500 C. More applied studies show that hot working generally improves the microstructure and therefore the strength of TiC and NbC. Sintering studies on UN indicate that very high densities can be achieved. Hot pressing of cermets of HfN and HfC produces good mechanical properties for high temperature bearing applications.

Antitumor Efficacy of 7β, 17α-Dimethyltestosterone (Calusterone) in Advanced Female Breast Cancer

PubMed Central

Gordan, Gilbert S.; Halden, Allan; Walter, Robert M.

1970-01-01

Twenty-two women with far advanced, hormone-refractory breast cancer were treated with 7β,17α dimethyltestosterone (calusterone), 150 to 300 mg per day by mouth, to test its antitumor efficacy. Using the strict criteria of the Cooperative Breast Cancer Group, 14 of the women (64 percent) obtained objective regressions. Regressions lasted for from 3 to 20 months, averaging 7 months. Undesirable actions are those of a 17α-alkylated, weak androgen with inconstant bromsulphalein retention, but without elevation of serum bilirubin levels or of hepatic enzymes. This compound has potent antitumor efficacy in women with advanced breast cancer, is better tolerated than most chemotherapeutic or steroidal antitumor agents, and will probably assume an important position in the care of these patients. ImagesFigure 1Figure 2Figure 3Figure 3Figure 4Figure 5Figure 5 PMID:5457511

Possible impact-induced refractory-lithophile fractionations in EL chondrites

NASA Astrophysics Data System (ADS)

Rubin, Alan E.; Huber, Heinz; Wasson, John T.

2009-03-01

Literature data show that refractory-lithophile elements in most chondrite groups are unfractionated relative to CI chondrites; the principal exception is the EL-chondrite group whose observed falls (all of which are type 6) are depleted in Ca and light REE. In contrast, literature data and our new INAA data on EL3 PCA 91020, EL3 MAC 88136 and EL4 Grein 002 show that some replicates of these samples have nearly flat REE patterns (unlike those of EL6 chondrites); other replicates exhibit fractionated REE patterns similar to those of EL6 chondrites. Petrographic examination shows that many EL6 (and some EL3 and EL4) chondrites are impact-melt breccias or contain impact-melted portions. We suggest that the same impact processes that formed these breccias and produced melt are responsible for the observed bulk compositional fractionations in refractory-lithophile elements, i.e., EL6 chondrites were produced from initially unequilibrated EL3 material. When large amounts of impact heat were deposited, plagioclase and/or oldhamite (CaS) (the major REE carriers in enstatite chondrites) may have been melted and then transported appreciable (>10 cm) distances. EL6 chondrites represent the residuum that is depleted in REE (particularly in LREE) and Ca. Unlike the case for EL chondrites, our new INAA data on ALH 84170, EET 87746 and SAH 97096 (all EH3) show some scatter but are consistent with the EH group having uniform refractory-lithophile abundances.

A 14-Year Experience in the Management of Patients with Acquired Immune Thrombotic Thrombocytopenic Purpura in Northern Israel.

PubMed

Rinott, Nadav; Mashiach, Tatiana; Horowitz, Netanel A; Schliamser, Liliana; Sarig, Galit; Keren-Politansky, Anat; Dann, Eldad J

2015-01-01

Acquired idiopathic thrombotic thrombocytopenic purpura (I-TTP) is a life-threatening microangiopathic disorder usually treated with therapeutic plasma exchange (TPE). The current study assessed the role of rituximab in the treatment of complicated I-TTP. The sequence of TTP events was compared in a group of I-TTP patients treated with TPE and a cohort of refractory or relapsed patients who also received rituximab. This retrospective evaluation included 45 I-TTP patients, treated between January 2000 and October 2013, who underwent at least 3 TPE procedures and were followed up until December 2013 or death. Thirty-one patients with an uncomplicated course received TPE only. Fourteen patients had a complicated course due to either a primary refractory/exacerbated disease (n = 5) or relapse (n = 9) and received rituximab together with TPE. The median number of TPE procedures performed in the first TTP episode in the uncomplicated cohort and groups with primary refractory or relapsed TTP was 11, 27 and 45, respectively. The relapse rates per follow-up year in the uncomplicated I-TTP, primary refractory and relapsed I-TTP groups were 0.18, 0.2 and 0.6 episodes, respectively. After rituximab therapy this rate dropped to 0.2 per year in the relapsed subgroup. In conclusion, about a quarter of patients with I-TTP had a complicated course and experienced a major benefit from rituximab in terms of effectiveness and safety. © 2015 S. Karger AG, Basel.

Clinical outcomes of Ahmed glaucoma valve implantation in pediatric glaucoma.

PubMed

Pakravan, Mohammad; Esfandiari, Hamed; Yazdani, Shahin; Doozandeh, Azadeh; Dastborhan, Zahra; Gerami, Ebrahim; Kheiri, Bahareh; Pakravan, Parastou; Yaseri, Mehdi; Hassanpour, Kiana

2018-03-01

To evaluate the outcomes of Ahmed glaucoma valve implantation in refractory primary congenital glaucoma as well as primary procedure in aphakic glaucoma. In this retrospective study, medical records of patients who underwent Ahmed glaucoma valve implantation for refractory glaucoma and aphakic glaucoma were reviewed. Primary outcome measures were the surgical success defined as intraocular pressure ≤21 mm Hg and decreased ≥20% and no secondary glaucoma surgery. Secondary outcome measures were the number of glaucoma medications, complications, best corrected visual acuity, and intraocular pressure. A total of 62 eyes of refractory primary congenital glaucoma patients (group 1) and 33 eyes of aphakic glaucoma patients (group 2) were included in our study. Mean follow-up was 51 ± 33 months in group 1 and 49 ± 41 months in group 2 (p = 0.82). The cumulative probability of success was 90% in both groups at the first year; however, the success rate was 52.5% in group 1 and 71.5% in group 2 at 5 years' follow-up visit. In group 1, the mean intraocular pressure ± standard deviation was 33.1 ± 8.6 mm Hg at the baseline and decreased to 17.1 ± 5.3 mm Hg at 1 year and 18.5 ± 6.4 at 3 years postoperatively (all p's < 0.001). Corresponding values for group 2 were 28.9 ± 6.1, 15.2 ± 4.6, and 16.0 ± 5.9 mm Hg, respectively (all p's < 0.001). The baseline number of glaucoma medications was 3 ± 0.7 that decreased to 2 ± 0.8 at final follow-up (p = 0.02). Ahmed glaucoma valve implantation has a moderate success rate in the management of refractory primary congenital glaucoma with an increased chance of tube-related complications. The surgical success rate is higher in case of primary Ahmed glaucoma valve implant for aphakic glaucoma with acceptable safety profile.

Sample Processing technique onboard ExoMars (MOMA) to analyze organic compounds by Gas Chromatography-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Buch, A.; Freissinet, C.; Sternberg, R.; Szopa, C.; Coll, P. J.; Brault, A.; Pinnick, V.; Siljeström, S.; Raulin, F.; Steininger, H.; Goesmann, F.; MOMA Team

2011-12-01

With the aim of separating and detecting organic compounds from Martian soil onboard the Mars Organic Molecule Analyzer (MOMA) experiment of the ExoMars 2018 upcoming joint ESA/NASA mission, we have developed three different space compatible sample preparation techniques compatible with space missions, able to extract and analyze by GC-MS a wide range of volatile and refractory compounds, including chirality analysis. Then, a sample processing utilizing three derivatization/extraction reactions has been carried out. The first reaction is based on a silyl reagent N-Methyl-N- (Tert-Butyldimethylsilyl)trifluoroacetamide (MTBSTFA) [1], the second one, N,N-Dimethylformamide Dimethylacetal (DMF-DMA) [2,3] is dedicated to the chirality detection and the third one is a thermochemolysis based on the use of tetramethylammoniumhydroxide (TMAH). The sample processing system is performed in an oven, dedicated to the MOMA experiment containing the solid sample (50-100mg). The internal temperature of the oven ranges from 20 to 900 °C. The extraction step is achieved by using thermodesorption in the range of 100 to 300°C for 5 to 20 min. Then, the chemical derivatization of the extracted compounds is performed directly on the soil sample by using a derivatyization capsule which contains a mixture of MTBSTFA-DMF or DMF-DMA solution when enantiomeric separation is required. By decreasing the polarity of the targeted molecules, this step allows their volatilization at a temperature below 250°C without any thermal degradation. Once derivatized, the volatile target molecules are trapped in a chemical trap and promptly desorbed into the gas chromatograph coupled to a mass spectrometer. Thermochemolysis is directly performed in the oven at 400°C during 5 min with a 25% (w/w) methanol solution of tetramethylammonium hydroxide (TMAH). Then, pyrolysis in the presence of TMAH allows both an efficient cleavage of polar bonds and the subsequent methylation of COOH, OH and NH2 groups, hence the release of less polar, GC-amenable compounds. By using thermochemolysis several families of biological molecules were detected such as fatty acids, n-alkenes and n-alkanols [4]. [1] A. Buch et al., Development of a gas chromatography compatible Sample Processing System (SPS) for the in-situ analysis of refractory organic matter in martian soil: preliminary result. Advances in Space Research 43, 143-151, 2009. [2] C. Freissinet et al., Journal of Chromatography A.1217 (5), 731-740, 2010. [3] U. Meierhenrich et al., Journal of Analytical and Applied Pyrolysis 60, 13-26, 2001. [4] C. Geffroy-Rodier et al., Journal of Analytical and Applied Pyrolysis, 85, 2009.

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.

Immunomodulation effects of mesenchymal stromal cells on acute graft-versus-host disease after hematopoietic stem cell transplantation.

PubMed

Zhao, Ke; Lou, Rui; Huang, Fen; Peng, Yanwen; Jiang, Zujun; Huang, Ke; Wu, Xiuli; Zhang, Yu; Fan, Zhiping; Zhou, Hongsheng; Liu, Can; Xiao, Yang; Sun, Jing; Li, Yangqiu; Xiang, Peng; Liu, Qifa

2015-01-01

Refractory acute graft-versus-host disease (aGVHD) is a major cause of death after allogeneic hematopoietic stem cell transplantation. This study evaluated the immunomodulation effects of mesenchymal stromal cells (MSCs) from bone marrow of a third-party donor for refractory aGVHD. Forty-seven patients with refractory aGVHD were enrolled: 28 patients receiving MSC and 19 patients without MSC treatment. MSCs were given at a median dose of 1 × 10(6) cells/kg weekly until patients got complete response or received 8 doses of MSCs. After 125 doses of MSCs were administered, with a median of 4 doses (range, 2 to 8) per patient, overall response rate was 75% in the MSC group compared with 42.1% in the non-MSC group (P = .023). The incidence of cytomegalovirus, Epstein-Barr virus infections, and tumor relapse was not different between the 2 groups during aGVHD treatment and follow-up. The incidence and severity of chronic GVHD in the MSC group were lower than those in the non-MSC group (P = .045 and P = .005). The ratio of CD3(+)CD4(+)/CD3(+)CD8(+) T cells, the frequencies of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), and the levels of signal joint T cell-receptor excision DNA circles (sjTRECs) after MSCs treatment were higher than those pretreatment. MSC-treated patients exhibited higher Tregs frequencies and sjTRECs levels than those in the non-MSC group at 8 and 12 weeks after treatment. MSCs derived from bone marrow of a third-party donor are effective to refractory aGVHD. It might reduce the incidence and severity of chronic GVHD in aGVHD patients by improving thymic function and induction of Tregs but not increase the risks of infections and tumor relapse. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Role of Polyamines in Parasite Cell Architecture and Function.

PubMed

Vannier-Santos, Marcos A; Suarez-Fontes, Ana M

2017-01-01

In the absence of accessible, effective vaccines, the fight against parasitic disease relies mostly on chemotherapy. Nevertheless, the considerable side effects, high costs and growing number of refractory cases comprise substantial drawbacks. Thus, the search for new antiparasitic compounds remains a high priority. The polyamine biosynthesis, conversion and transport pathways offer different targets for selective chemotherapy. Polyamine analogues and other antagonists may provide tools in the search for new lead compounds. Light and electron microscopy techniques may encompass valuable approaches to elucidate the possible mechanisms of action of different antiparasitic compounds, allowing the identification of subcellular target compartments, presumably establishing the basis for a more rational drug design and/or planning of therapeutic strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Detection of Organics at Mars: How Wet Chemistry Onboard SAM Helps

NASA Technical Reports Server (NTRS)

Buch, A.; Freissinet, Caroline; Szopa, C.; Glavin, D.; Coll, P.; Cabane, M.; Eigenbrode, J.; Navarro-Gonzalez, R.; Coscia, D.; Teinturier, S.;

Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma.

PubMed

Lonial, Sagar; Dimopoulos, Meletios; Palumbo, Antonio; White, Darrell; Grosicki, Sebastian; Spicka, Ivan; Walter-Croneck, Adam; Moreau, Philippe; Mateos, Maria-Victoria; Magen, Hila; Belch, Andrew; Reece, Donna; Beksac, Meral; Spencer, Andrew; Oakervee, Heather; Orlowski, Robert Z; Taniwaki, Masafumi; Röllig, Christoph; Einsele, Hermann; Wu, Ka Lung; Singhal, Anil; San-Miguel, Jesus; Matsumoto, Morio; Katz, Jessica; Bleickardt, Eric; Poulart, Valerie; Anderson, Kenneth C; Richardson, Paul

2015-08-13

Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma. In this phase 3 study, we randomly assigned patients to receive either elotuzumab plus lenalidomide and dexamethasone (elotuzumab group) or lenalidomide and dexamethasone alone (control group). Coprimary end points were progression-free survival and the overall response rate. Final results for the coprimary end points are reported on the basis of a planned interim analysis of progression-free survival. Overall, 321 patients were assigned to the elotuzumab group and 325 to the control group. After a median follow-up of 24.5 months, the rate of progression-free survival at 1 year in the elotuzumab group was 68%, as compared with 57% in the control group; at 2 years, the rates were 41% and 27%, respectively. Median progression-free survival in the elotuzumab group was 19.4 months, versus 14.9 months in the control group (hazard ratio for progression or death in the elotuzumab group, 0.70; 95% confidence interval, 0.57 to 0.85; P<0.001). The overall response rate in the elotuzumab group was 79%, versus 66% in the control group (P<0.001). Common grade 3 or 4 adverse events in the two groups were lymphocytopenia, neutropenia, fatigue, and pneumonia. Infusion reactions occurred in 33 patients (10%) in the elotuzumab group and were grade 1 or 2 in 29 patients. Patients with relapsed or refractory multiple myeloma who received a combination of elotuzumab, lenalidomide, and dexamethasone had a significant relative reduction of 30% in the risk of disease progression or death. (Funded by Bristol-Myers Squibb and AbbVie Biotherapeutics; ELOQUENT-2 ClinicalTrials.gov number, NCT01239797.).

Outcomes after use of two standard ablative regimens in patients with refractory acute myeloid leukaemia: a retrospective, multicentre, registry analysis.

PubMed

Nagler, Arnon; Savani, Bipin N; Labopin, Myriam; Polge, Emmanuelle; Passweg, Jakob; Finke, Jürgen; Kyrcz-Krzemien, Slawomira; Volin, Liisa; Anagnostopoulos, Achilles; Aljurf, Mahmoud; Beelen, Dietrich W; Vigouroux, Stephane; Milpied, Noel; Suarez, Felipe; Mohty, Mohamad

2015-09-01

Cyclophosphamide plus intravenous busulfan has not been compared with cyclophosphamide plus total body irradiation (TBI) in adults with advanced refractory acute myeloid leukaemia before allogeneic haemopoietic stem-cell transplantation (HCT). We aimed to assess whether survival of patients receiving ablative intravenous busulfan-based conditioning regimens before a related or volunteer-unrelated donor HCT for refractory acute myeloid leukaemia is not inferior to that of patients receiving an ablative TBI-based regimen. In this retrospective, multicentre, registry-based study, we obtained data for patients (aged >18 years) with refractory acute myeloid leukaemia in active phase of disease, who had received HCT from an HLA-identical sibling or an unrelated donor after intravenous busulfan plus cyclophosphamide or cyclophosphamide plus TBI conditioning between 2000 and 2012. Data was obtained from the European Group for Blood and Marrow Transplantation registry. The primary endpoints of the study were overall survival and leukaemia-free survival. We obtained data for 514 patients who had received intravenous busulfan plus cyclophosphamide and 338 patients who had received cyclophosphamide plus TBI. The median percentage of blasts before HCT did not differ significantly between groups (20% [range 5-100; IQR 10-32] in the intravenous busulfan plus cyclophosphamide group vs 16% [5-95; 9-33] in the cyclophosphamide plus TBI group; p=0·16). Overall survival at 2 years did not differ between the groups in the univariate analysis (31·2% [95% CI 26·8-35·5] with intravenous busulfan plus cyclophosphamide vs 33·4% [28·1-38·7] wth cyclophosphamide plus TBI; p=0·65). Leukaemia-free survival at 2 years also did not differ between groups (25·0% [95% CI 21·0-29·0] vs 28·4% [23·4-33·5]; p=0·47). In multivariable analysis adjusting for differences between both groups, no difference was noted between the two groups in terms of overall survival (hazard ratio [HR] 0·99 [95% CI 0·83-1·20]; p=0·95) or leukaemia-free survival (HR 0·97 [0·81-1·16]; p=0·71). Main causes of non-relapse mortality were graft-versus-host disease (49 [10%] in the intravenous busulfan plus cyclophosphamide group vs 25 [7%] in the cyclophosphamide plus TBI group) and infection (36 [7%] vs 18 [5%]). From a practical standpoint, the use of intravenous busulfan plus cyclophosphamide is likely to be a valid and efficient alternative to cyclophosphamide plus TBI conditioning regimen for patients with refractory acute myeloid leukaemia, especially for those transplant centres without access to radiation facilities. None. Copyright © 2015 Elsevier Ltd. All rights reserved.

Intravenous flurbiprofen axetil enhances analgesic effect of opioids in patients with refractory cancer pain by increasing plasma β-endorphin.

PubMed

Wu, Ting-Ting; Wang, Zhi-Gang; Ou, Wu-Ling; Wang, Jun; Yao, Guo-Qing; Yang, Bo; Rao, Zhi-Guo; Gao, Jian-Fei; Zhang, Bi-Cheng

2014-01-01

The study aimed to investigate the analgesic effect of a combination of intravenous flurbiprofen axetil and opioids, and evaluate the relationship between refractory pain relief and plasma β-endorphin levels in cancer patients. A total of 120 cancer patients was randomly divided into two groups, 60 patients took orally morphine sulfate sustained-release tablets in group A, and another 60 patients receiving the combination treatment of intravenous flurbiprofen axetil and opioid drugs in group B. After 7 days, pain relief, quality of life improvement and side effects were evaluated. Furthermore, plasma β-endorphin levels were measured by radioimmunoassay. With the combination treatment of intravenous intravenous flurbiprofen axetil and opioids, the total effective rate of pain relief rose to 91.4%, as compared to 82.1% when morphine sulfate sustained-release tablet was used alone. Compared with that of group A, the analgesic effect increased in group B (p=0.031). Moreover, satisfactory pain relief was associated with a significant increase in plasma β-endorphin levels. After the treatment, plasma β-endorphin level in group B was 62.4±13.5 pg/ml, which was higher than that in group A (45.8±11.2 pg/ml) (p<0.05). Our results suggest the combination of intravenous flurbiprofen axetil and opioids can enhance the analgesic effect of opioid drugs by increasing plasma β-endorphin levels, which would offer a selected and reliable strategy for refractory cancer pain treatment.

Evaluation of mitoguazone in patients with refractory chronic lymphocytic leukemia: a phase II study (P-H482) of the Eastern Cooperative Oncology Group.

PubMed

Wiernik, P H; Gordon, L I; Oken, M M; Harris, J E; O'Connell, M J

1999-10-01

Mitoguazone is a unique antitumor agent that interferes with polyamine synthesis that has been reported to have activity against AIDS-related malignant lymphoma. We, therefore, tested this agent for activity against chronic lymphocytic leukemia (CLL) in this phase II study. Mitoguazone, 500 mg/M2 was given intravenously weekly to 13 patients with relapsed or refractory, previously treated Rai stages 2-4 CLL. There were no complete or partial responses as judged by standard criteria. Toxicity was acceptable. Mitoguazone in the dose and schedule employed in this study has no significant activity as a single agent in patients with relapsed or refractory CLL.

Clinical management and outcome of refractory asthma in the UK from the British Thoracic Society Difficult Asthma Registry.

PubMed

Sweeney, Joan; Brightling, Chris E; Menzies-Gow, Andrew; Niven, Robert; Patterson, Chris C; Heaney, Liam G

2012-08-01

Refractory asthma represents a significant unmet clinical need. Data from a national online registry audited clinical outcome in 349 adults with refractory asthma from four UK specialist centres in the British Thoracic Society Difficult Asthma Network. At follow-up, lung function improved, with a reduction in important healthcare outcomes, specifically hospital admission, unscheduled healthcare visits and rescue courses of oral steroids. The most frequent therapeutic intervention was maintenance oral corticosteroids and most steroid sparing agents (apart from omalizumab) demonstrated minimal steroid sparing benefit. A significant unmet clinical need remains in this group, specifically a requirement for therapies which reduce systemic steroid exposure.

Treatment of central venous in-stent restenosis with repeat stent deployment in hemodialysis patients.

PubMed

Ronald, James; Davis, Bradley; Guevara, Carlos J; Pabon-Ramos, Waleska M; Smith, Tony P; Kim, Charles Y

2017-05-15

To report patency rates for stent deployment for treatment of in-stent stenosis of the central veins of the chest in hemodialysis patients. A retrospective analysis was performed on 29 patients who underwent 35 secondary percutaneous transluminal stent (PTS) deployments for in-stent stenosis within the central veins that were refractory to angioplasty and ipsilateral to a functioning hemodialysis access (in-stent PTS group). For comparison, patency data were acquired for 47 patients who underwent 78 successful percutaneous transluminal angioplasty (PTA) procedures for in-stent stenosis (in-stent PTA group) and 55 patients who underwent 55 stent deployments within native central vein stenosis refractory to angioplasty (native vein PTS group). The 3-, 6-, and 12-month primary lesion patency for the in-stent PTS group was 73%, 57%, and 32%, respectively. The 3-, 6-, and 12-month primary patency for the in-stent PTA group was 70%, 38%, and 17% and for the native vein PTS group was 78%, 57%, and 26%, which were similar to the in-stent PTS group (p = 0.20 and 0.41, respectively). The 3-, 6-, and 12-month secondary access patency was 91%, 73%, and 65% for the in-stent PTS group. Sub-analysis of the in-stent PTS group revealed no difference in primary (p = 0.93) or secondary patency rates (p = 0.27) of bare metal stents (n = 23) compared with stent grafts (n = 12). Stent deployment for central vein in-stent stenosis refractory to angioplasty was associated with reasonable patency rates, which were similar to in-stent PTA and native vein PTS.

A Randomized Clinical Trial of Preoperative Administration of Branched-Chain Amino Acids to Prevent Postoperative Ascites in Patients with Liver Resection for Hepatocellular Carcinoma.

PubMed

Kikuchi, Yutaro; Hiroshima, Yukihiko; Matsuo, Kenichi; Kawaguchi, Daisuke; Murakami, Takashi; Yabushita, Yasuhiro; Endo, Itaru; Taguri, Masataka; Koda, Keiji; Tanaka, Kuniya

2016-10-01

Massive postoperative ascites remains a major threat that can lead to liver failure and other fatal complications, especially in patients with poor liver function. Branched-chain amino acid (BCAA) administration increases biosynthesis and secretion of albumin by hepatocytes and increases oncotic pressure by elevating blood albumin concentration, thereby decreasing peripheral edema, ascites, and pleural effusion. We randomly allocated consecutive patients undergoing major liver resection for hepatocellular carcinoma to either a group where oral BCAA administration was initiated 3 weeks before liver resection, or a non-BCAA group. The primary study endpoint was development of postoperative ascites. Overall, 39 patients were allocated to the BCAA group, while 38 were assigned to the non-BCAA group. No significant difference in the rate of refractory ascites, considered alone, was evident between the BCAA (5.1 %) and non-BCAA groups (13.2 %; p = 0.263). However, the occurrence of refractory ascites and/or pleural effusion was significantly less frequent in the BCAA group (5.1 %) than in the non-BCAA group (21.1 %; p = 0.047). Furthermore, the postoperative serum concentration of reduced-state albumin was greater immediately after liver resection in the BCAA group than in the non-BCAA group. Preoperative administration of BCAA did not significantly improve prevention of refractory ascites, but significant effectiveness in preventing ascites, pleural effusion, or both, as well as improving metabolism of albumin, was demonstrated [University Hospital Medical Information Network (UMIN) reference number 000004244].

Administration of recombinant activated factor VII in the intensive care unit after complex cardiovascular surgery: clinical and economic outcomes.

PubMed

Uber, Walter E; Toole, John M; Stroud, Martha R; Haney, Jason S; Lazarchick, John; Crawford, Fred A; Ikonomidis, John S

2011-06-01

Refractory bleeding after complex cardiovascular surgery often leads to increased length of stay, cost, morbidity, and mortality. Recombinant activated factor VII administered in the intensive care unit can reduce bleeding, transfusion, and surgical re-exploration. We retrospectively compared factor VII administration in the intensive care unit with reoperation for refractory bleeding after complex cardiovascular surgery. From 1501 patients who underwent cardiovascular procedures between December 2003 and September 2007, 415 high-risk patients were identified. From this cohort, 24 patients were divided into 2 groups based on whether they either received factor VII in the intensive care unit (n = 12) or underwent reoperation (n = 12) for refractory bleeding. Preoperative and postoperative data were collected to compare efficacy, safety, and economic outcomes. In-hospital survival for both groups was 100%. Factor VII was comparable with reoperation in achieving hemostasis, with both groups demonstrating decreases in chest tube output and need for blood products. Freedom from reoperation was achieved in 75% of patients receiving factor VII, whereas reoperation was effective in achieving hemostasis alone in 83.3% of patients. Prothrombin time, international normalized ratio, and median operating room time were significantly less (P < .05) in patients who received factor VII. Both groups had no statistically significant differences in other efficacy, safety, or economic outcomes. Factor VII administration in the intensive care unit appears comparable with reoperation for refractory bleeding after complex cardiovascular surgical procedures and might represent an alternative to reoperation in selected patients. Future prospective, randomized controlled trials might further define its role. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

The role of gastroesophageal reflux in relation to symptom onset in patients with proton pump inhibitor-refractory nonerosive reflux disease accompanied by an underlying esophageal motor disorder.

PubMed

Izawa, Shinya; Funaki, Yasushi; Iida, Akihito; Tokudome, Kentaro; Tamura, Yasuhiro; Ogasawara, Naotaka; Sasaki, Makoto; Kasugai, Kunio

2014-01-01

The symptom improvement rate is low with proton pump inhibitors (PPIs) in nonerosive reflux disease (NERD). The underlying pathogenic mechanism is complex. Esophageal motility disorders (EMDs) are thought to be a factor, but their prevalence, type, symptoms and the role played by gastroesophageal reflux (GER) in symptom onset have not been fully investigated. To investigate the role of GER in symptom onset in PPI-refractory NERD patients with EMDs. This study comprised 76 patients with PPI-refractory NERD. Manometry was performed during PPI treatment and patients were divided into an EMD group and normal motility (non-EMD) group. Then, multichannel intraluminal impedance-pH monitoring was performed and medical interviews were conducted. Nineteen patients (25%) had an EMD. Data were compared between 17 patients, excluding 2 with achalasia and 57 non-EMD patients. No significant differences were observed between groups in 24-hour intraesophageal pH <4 holding time (HT), mean number of GER episodes or mean number of proximal reflux episodes. The reflux-related symptom index (≥50%) showed a relationship between reflux and symptoms in 70.5% of EMD patients and 75% of non-EMD patients. In the EMD group, the score for FSSG (Frequency Scale for the Symptoms of GERD) question (Q)10 was significantly correlated with the number of GER episodes (r = 0.58, p = 0.02) and the number of proximal reflux episodes (r = 0.63, p = 0.02). In addition, the score for Q9 tended to be correlated with the number of GER episodes (r = 0.44, p = 0.06). Our results suggest that some PPI-refractory NERD patients have EMDs, and that GER plays a role in symptom onset.

Similar outcome of allogeneic stem cell transplantation after myeloablative and sequential conditioning regimen in patients with refractory or relapsed acute myeloid leukemia: A study from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire.

PubMed

Decroocq, Justine; Itzykson, Raphaël; Vigouroux, Stéphane; Michallet, Mauricette; Yakoub-Agha, Ibrahim; Huynh, Anne; Beckerich, Florence; Suarez, Felipe; Chevallier, Patrice; Nguyen-Quoc, Stéphanie; Ledoux, Marie-Pierre; Clement, Laurence; Hicheri, Yosr; Guillerm, Gaëlle; Cornillon, Jérôme; Contentin, Nathalie; Carre, Martin; Maillard, Natacha; Mercier, Mélanie; Mohty, Mohamad; Beguin, Yves; Bourhis, Jean-Henri; Charbonnier, Amandine; Dauriac, Charles; Bay, Jacques-Olivier; Blaise, Didier; Deconinck, Eric; Jubert, Charlotte; Raus, Nicole; Peffault de Latour, Regis; Dhedin, Nathalie

2018-03-01

Patients with acute myeloid leukemia (AML) in relapse or refractory to induction therapy have a dismal prognosis. Allogeneic hematopoietic stem cell transplantation is the only curative option. In these patients, we aimed to compare the results of a myeloablative transplant versus a sequential approach consisting in a cytoreductive chemotherapy followed by a reduced intensity conditioning regimen and prophylactic donor lymphocytes infusions. We retrospectively analyzed 99 patients aged 18-50 years, transplanted for a refractory (52%) or a relapsed AML not in remission (48%). Fifty-eight patients received a sequential approach and 41 patients a myeloablative conditioning regimen. Only 6 patients received prophylactic donor lymphocytes infusions. With a median follow-up of 48 months, 2-year overall survival was 39%, 95% confidence interval (CI) (24-53) in the myeloablative group versus 33%, 95% CI (21-45) in the sequential groups (P = .39), and 2-year cumulative incidence of relapse (CIR) was 57% versus 50% respectively (P = .99). Nonrelapse mortality was not higher in the myeloablative group (17% versus 15%, P = .44). In multivariate analysis, overall survival, CIR and nonrelapse mortality remained similar between the two groups. However, in multivariate analysis, sequential conditioning led to fewer acute grade II-IV graft versus host disease (GVHD) (HR for sequential approach = 0.37; 95% CI: 0.21-0.65; P < .001) without a significant impact on chronic GVHD (all grades and extensive). In young patients with refractory or relapsed AML, myeloablative transplant and sequential approach offer similar outcomes except for a lower incidence of acute GvHD after a sequential transplant. © 2018 Wiley Periodicals, Inc.

Comparison of Ifosfamide, Carboplatin and Etoposide versus Etoposide, Steroid, and Cytarabine Cisplatin as Salvage Chemotherapy in Patients with Refractory or Relapsed Hodgkin's lymphoma

PubMed Central

Mehrzad, Valiollah; Ashrafi, Farzaneh; Farrashi, Ali Reza; Pourmarjani, Reyhaneh; Dehghani, Mehdi; Shahsanaei, Armindokht

2017-01-01

Background: Refractory or relapsed Hodgkin's disease (HD) occurs in 10-50% of patients. The treatment of choice for these patients is high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Response to salvage chemotherapy (SCT) partial remission (PR) is necessary before HDCT with ASCT. However, its applicability is restricted mostly to patients responding to salvage chemotherapy. Optimal salvage regimen for these patients is unclear. In this study, our aim was to compare the efficacy profiles of ifosfamide, carboplatin, and etoposide (ICE) and etoposide-steroid-cytarabine-cisplatin (ESHAP) (cytosine arabinoside, cisplatin, and dexamethasone) regimens in the salvage treatment of relapsed or refractory HD. Materials and Methods: In this retrospective analysis, 114 patients with primary refractory or relapsed HD who received ICE or ESHAP salvage regimen were included. Results: Of 114 patients, 47 (41.2%) were females and the median age was 31.5 years. Response could be evaluated in 114 patients. Of 114 patients, 38 (33%) achieved complete remission (CR) and 21 (18.4%) achieved PR, leading to an overall response rate (ORR: CR + PR) of 51.4%. In the evaluable ICE group (n = 41), rates of CR, PR, and ORR were 21.9%, 17.1%, and 39% and in the ESHAP group (n = 73), rates of CR, PR, and ORR were 39.7%, 19.2%, and 58.9% (for ORR, P = 0.04), respectively. Conclusion: In patients with relapsed or refractory HD, treatment with ESHAP seems to have higher rates of response than ICE regimen does. PMID:28401077

Bolus versus continuous low dose of enalaprilat in congestive heart failure with acute refractory decompensation.

PubMed

Podbregar, M; Voga, G; Horvat, M; Zuran, I; Krivec, B; Skale, R; Pareznik, R

1999-01-01

The first dose of angiotensin-converting enzyme (ACE) inhibitors may trigger a considerable fall of blood pressure in chronic heart failure. The response may be dose-related. To determine hemodynamic and systemic oxygenation effects of low-dose enalaprilat, we administered intravenous enalaprilat (0.004 mg/kg) as bolus (group B) or continuous 1-hour infusion (group C) in 20 patients with congestive heart failure due to ischemic heart disease with acute decompensation refractory to inotropic, vasodilator and diuretic therapy. Hemodynamic and systemic oxygenation variables were recorded at baseline (+0 min), +30, +60, +120, +180, and +360 min after the start of intervention. Mean arterial pressure (MAP) (p < 0. 001), mean pulmonary artery pressure (MPAP) (p < 0.001), pulmonary artery occlusion pressure (PAOP) (p < 0.001), oxygen extraction ratio (ER) (p < 0.026) decreased regardless of enalaprilat application. Compared to group B, there was in group C prolonged decrease of MAP, MPAP, PAOP, ER and increase of pulmonary artery oxyhemoglobin saturation in regard to baseline values. Cardiac index, heart rate, central venous pressure and oxygen consumption index did not change. A low dose of intravenous enalaprilat (0.004 mg/kg) can be used to safely improve hemodynamics and systemic oxygenation in congestive heart failure due to ischemic heart disease with acute refractory decompensation.

Refining a complex nickel alloy to remove a sulfur impurity during vacuum induction melting: Part II

NASA Astrophysics Data System (ADS)

Sidorov, V. V.; Min, P. G.

2014-12-01

The results of studying the refining of complexly alloyed nickel melts from sulfur during melting in a vacuum induction furnace or with the use of an oxide calcium crucible, metallic calcium added to a melt, or rare-earth metals additions (which form thermodynamically stable refractory compounds with sulfur and, thus, eliminate the harmful effect of sulfur in the alloys) are reported.

The development of Nb-based advanced intermetallic alloys for structural applications

NASA Astrophysics Data System (ADS)

Subramanian, P. R.; Mendiratta, M. G.; Dimiduk, D. M.

1996-01-01

A new generation of refractory material systems with significant increases in temperature capability is required to meet the demands of future aerospace applications. Such materials require a balance of properties such as low-temperature damage tolerance, high-temperature strength, creep resistance, and superior environmental stability for implementation in advanced aerospace systems. Systems incorporating niobium-based beta alloys and intermetallic compounds have the potential for meeting these requirements.

Relation of Salivary PAF Periodontal Disease in Periodontal Maintenance and Refractory Periodontitis Patients

DTIC Science & Technology

1991-05-01

Knox, 1974). Studies have demonstrated the presence of streptococci and lactobacilli throughout the oral cavity , as well as in developing dental... oral cavity , it is apparent that these compounds have the potential to play a role in the initiation and progression of inflammatory oral disease...junctional epithelium and into the gingival sulcus and oral cavity . The perivascular connective tissue matrix becomes altered most likely by

The growth of Scenedesmus quadricauda in RO concentrate and the impacts on refractory organic matter, Escherichia coli, and trace organic compounds.

PubMed

Maeng, Sung Kyu; You, Song Hee; Nam, Joo-Youn; Ryu, Hodon; Timmes, Thomas C; Kim, Hyun-Chul

2018-05-01

This study achieves a better operational simplicity for the phycoremediation of reverse osmosis (RO) concentrate using Scenedesmus quadricauda microalgae. Under continuous illumination with CO 2 supplementation, algal growth in the RO concentrate resulted in a conversion of polymeric organic matter (a mixture of humic substances and polysaccharides) to biodegradable fractions and their prompt removal along with inorganic nutrients (NO 3 - and PO 4 3- ). The algal-induced degradation of humic-like substances which are typically refractory to microbial decomposition was demonstrated in an indirect manner. In this study, we also investigated the effects of algal treatment on the growth of Escherichia coli and removal of trace organic compounds (TOrCs) from the RO concentrate. Our results indicate that algal treatment of the RO concentrate using aeration with 10% (v/v) CO 2 under continuous illumination is highly feasible as a safe and inexpensive technology to remove non- or slowly-biodegradable organic matter, reduce enteric bacteria, and attenuate TOrCs in wastewater. However, the results should not be generalized, but critically discussed, due to limitations of using the synthetic RO concentrate in evaluating the performance of wastewater remediation with microalgae. Copyright © 2018 Elsevier Ltd. All rights reserved.

The influence of geometrical characteristics on the photocatalytic activity of TiO2 nanotube arrays for degradation of refractory organic pollutants in wastewater.

PubMed

Noeiaghaei, T; Yun, J-H; Nam, S W; Zoh, K D; Gomes, V G; Kim, J O; Chae, S R

2015-01-01

The effects of geometrical characteristics such as surface area (SA) and porosity of TiO2 nanotube arrays (TNAs) on its photocatalytic activity were investigated by applying variable voltages and reaction times for the anodization of Ti substrates. While larger SA of nanotubes was observed under higher applied potential, the porosity of TNAs decreased by increasing anodizing voltage. Under applied potential of 80 V, the SA of TNAs increased from 0.164 to 0.471 m2/g as anodization time increased from 1 to 5 hours, respectively. However, no significant effect on the porosity of TNAs was observed. On the other hand, both SA and porosity of TNAs, synthesized at 60 V, increased by augmenting the anodization time from 1 to 3 hours. But further increasing of anodization time to 5 hours resulted in a decreased SA of TNAs with no effect on their porosity. Accordingly, the TNAs with SA of 0.368 m2/g and porosity of 47% showed the highest photocatalytic activity for degradation of 4-chlorobenzoic acid (4CBA). Finally, the degradation of refractory model compounds such as carbamazepine and bisphenol-A was tested and more than 50% of both compounds could be degraded under UV-A irradiation (λmax=365 nm).

Ex-vivo sensitivity profiling to guide clinical decision making in acute myeloid leukemia: A pilot study.

PubMed

Swords, Ronan T; Azzam, Diana; Al-Ali, Hassan; Lohse, Ines; Volmar, Claude-Henry; Watts, Justin M; Perez, Aymee; Rodriguez, Ana; Vargas, Fernando; Elias, Roy; Vega, Francisco; Zelent, Arthur; Brothers, Shaun P; Abbasi, Taher; Trent, Jonathan; Rangwala, Shaukat; Deutsch, Yehuda; Conneally, Eibhlin; Drusbosky, Leylah; Cogle, Christopher R; Wahlestedt, Claes

2018-01-01

A precision medicine approach is appealing for use in AML due to ease of access to tumor samples and the significant variability in the patients' response to treatment. Attempts to establish a precision medicine platform for AML, however, have been unsuccessful, at least in part due to the use of small compound panels and having relatively slow turn over rates, which restricts the scope of treatment and delays its onset. For this pilot study, we evaluated a cohort of 12 patients with refractory AML using an ex vivo drug sensitivity testing (DST) platform. Purified AML blasts were screened with a panel of 215 FDA-approved compounds and treatment response was evaluated after 72h of exposure. Drug sensitivity scoring was reported to the treating physician, and patients were then treated with either DST- or non-DST guided therapy. We observed survival benefit of DST-guided therapy as compared to the survival of patients treated according to physician recommendation. Three out of four DST-treated patients displayed treatment response, while all of the non-DST-guided patients progressed during treatment. DST rapidly and effectively provides personalized treatment recommendations for patients with refractory AML. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Medical versus surgical treatment for refractory or recurrent peptic ulcer.

PubMed

Gurusamy, Kurinchi Selvan; Pallari, Elena

2016-03-29

Refractory peptic ulcers are ulcers in the stomach or duodenum that do not heal after eight to 12 weeks of medical treatment or those that are associated with complications despite medical treatment. Recurrent peptic ulcers are peptic ulcers that recur after healing of the ulcer. Given the number of deaths due to peptic ulcer-related complications and the long-term complications of medical treatment (increased incidence of fracture), it is unclear whether medical or surgical intervention is the better treatment option in people with recurrent or refractory peptic ulcers. To assess the benefits and harms of medical versus surgical treatment for people with recurrent or refractory peptic ulcer. We searched the specialised register of the Cochrane Upper GI and Pancreatic Diseases group, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and trials registers until September 2015 to identify randomised trials and non-randomised studies, using search strategies. We also searched the references of included studies to identify further studies. We considered randomised controlled trials and non-randomised studies comparing medical treatment with surgical treatment in people with refractory or recurrent peptic ulcer, irrespective of language, blinding, or publication status for inclusion in the review. Two review authors independently identified trials and extracted data. We planned to calculate the risk ratio, mean difference, standardised mean difference, or hazard ratio with 95% confidence intervals using both fixed-effect and random-effects models with Review Manager 5 based on intention-to-treat analysis. We included only one non-randomised study published 30 years ago in the review. This study included 77 participants who had gastric ulcer and in whom medical therapy (histamine H2 receptor blockers, antacids, and diet) had failed after an average duration of treatment of 29 months. The authors do not state whether these were recurrent or refractory ulcers. It appears that the participants did not have previous complications such as bleeding or perforation. Of the 77 included participants, 37 participants continued to have medical therapy while 40 participants received surgical therapy (antrectomy with or without vagotomy; subtotal gastrectomy with or without vagotomy; vagotomy; pyloroplasty and suture of the ulcer; suture or closure of ulcer without vagotomy or excision of the ulcer; proximal gastric or parietal cell vagotomy alone; suture or closure of the ulcer with proximal gastric or parietal cell vagotomy). Whether to use medical or surgical treatment was determined by participant's or treating physician's preference.The study authors reported that two participants in the medical treatment group (2 out of 37; 5.4%) had gastric cancer, which was identified by repeated biopsy. They did not report the proportion of participants who had gastric cancer in the surgical treatment group. They also did not report the implications of the delayed diagnosis of gastric cancer in the medical treatment group. They did not report any other outcomes of interest for this review (that is health-related quality of life (using any validated scale), adverse events and serious adverse events, peptic ulcer bleeding, peptic ulcer perforation, abdominal pain, and long-term mortality). We found no studies that provide the relative benefits and harms of medical versus surgical treatment for recurrent or refractory peptic ulcers. Studies that evaluate the natural history of recurrent and refractory peptic ulcers are urgently required to determine whether randomised controlled trials comparing medical versus surgical management in patients with recurrent or refractory peptic ulcers or both are necessary. Such studies will also provide information for the design of such randomised controlled trials. A minimum follow-up of two to three years will allow the calculation of the incidence of complications and gastric cancer (in gastric ulcers only) in recurrent and refractory peptic ulcers. In addition to complications related to treatment and disease, health-related quality of life and loss of productivity should also be measured.

Psychoeducation and cognitive-behavioral therapy for patients with refractory bipolar disorder: a 5-year controlled clinical trial.

PubMed

González Isasi, A; Echeburúa, E; Limiñana, J M; González-Pinto, A

2014-03-01

The aim of this research, which represents an additional and longer follow-up to a previous trial, was to evaluate a 5-year follow-up study of a combined treatment (pharmacological+psychoeducational and cognitive-behavioral therapy) as compared with a standard pharmacological treatment in patients with refractory bipolar disorder. Forty patients were randomly assigned to either an Experimental group-under combined treatment - or a Control group - under pharmacological treatment. Data were analyzed by analysis of variance (ANOVA), with repeated measures at different evaluation time points. Between-group differences were significant at all evaluation time points after treatment. Experimental group had less hospitalization events than Control group in the 12-month evaluation (P=0.015). The Experimental group showed lower depression and anxiety in the 6-month (P=0.006; P=0.019), 12-month (P=0.001; P<0.001) and 5-year (P<0.001, P<0.001) evaluation time points. Significant differences emerged in mania and misadjustment already in the post-treatment evaluation (P=0.009; P<0.001) and were sustained throughout the study (6-month: P=0.006, P<0.001; 12-month: P<0.001, P<0.001; 5-year: P=0.004, P<0.001). After 5-year follow-up, 88.9% of patients in the Control group and 20% of patients in the Experimental group showed persistent affective symptoms and/or difficulties in social-occupational functioning. A combined therapy is long-term effective for patients with refractory bipolar disorder. Suggestions for future research are commented. Published by Elsevier Masson SAS.

Absorption and scattering properties of organic carbon vs. sulfate dominant aerosols at Gosan climate observatory in Northeast Asia

NASA Astrophysics Data System (ADS)

Lim, S.; Lee, M.; Kim, S.-W.; Yoon, S.-C.; Lee, G.; Lee, Y.

2013-12-01

Carbonaceous and soluble ionic species of PM1.0 and PM10 were measured along with the absorption and scattering properties and aerosol number size distributions at Gosan climate observatory (GCO) from January to September 2008. The daily averaged equivalent black carbon (EBC) measured as aerosol absorption exhibited two types of spectral dependence with a distinct maximum (peak) at either 370 nm or 880 nm, by which two subsets were extracted and classified into the respective groups (370 nm and 880 nm). The 370 nm group was distinguished by high organic carbon (OC) concentrations relative to elemental carbon (EC) and sulfate, but sulfate was predominant for the 880 nm group. The PM1.0 OC of the 370 nm group was mainly composed of refractory and pyrolized components that correlated well with PM1.0 EC1, referred to as char EC, which suggests biofuel and biomass combustion as the source of these OC fractions, particularly during winter. The scanning electron microscope (SEM) images and the number size distributions implied that aerosols of the 370 nm group were externally mixed upon transport in fast-moving air masses that passed through the Beijing area in about one day. In contrast, the aerosols of the 880 nm group were characterized by high sulfate concentrations, and seemed to be internally mixed during slow transport over the Yellow Sea region over approximately two to four days. The absorption and scattering coefficients of the 880 nm group were noticeably higher compared to those of the 370 nm group. The average absorption ångström exponent (AAE) was estimated to be 1.29 and 1.0 for the 370 nm and 880 nm groups, respectively, in the range 370-950 nm. These results demonstrated that the optical properties of aerosols were intimately linked to chemical composition and mixing state, characteristics determined both by source and atmospheric aging processes. In OC dominant aerosols, absorption was enhanced in the UV region, which was possibly due to refractory and pyrolized OC compounds. Under sulfate dominant conditions, the sulfate coating on BC particles contributed to the absorption of the longer visible light. Consequently, single scattering albedo (SSA) was higher for the 880 nm group than for the 370 nm group, emphasizing that the relative abundances of absorbing and scattering constituents are also important in estimating the climate effect of aerosols.

Absorption and scattering properties of organic carbon versus sulfate dominant aerosols at Gosan climate observatory in Northeast Asia

NASA Astrophysics Data System (ADS)

Lim, S.; Lee, M.; Kim, S.-W.; Yoon, S.-C.; Lee, G.; Lee, Y. J.

2014-08-01

Carbonaceous and soluble ionic species of PM1.0 and PM10 were measured along with the absorption and scattering properties and aerosol number size distributions at Gosan Climate Observatory (GCO) from January to September 2008. The daily averaged equivalent black carbon (EBC) measured as aerosol absorption exhibited two types of spectral dependence with a distinct maximum (peak) at either 370 nm or 880 nm, by which two subsets were extracted and classified into the respective groups (370 and 880 nm). The 370 nm group was distinguished by high organic carbon (OC) concentrations relative to elemental carbon (EC) and sulfate, but sulfate was predominant for the 880 nm group. The PM1.0 OC of the 370 nm group was mainly composed of refractory and pyrolized components that correlated well with PM1.0 EC1, referred to as char EC, which suggests biofuel and biomass combustion as the source of these OC fractions, particularly during winter. The scanning electron microscope (SEM) images and the number size distributions implied that aerosols of the 370 nm group were externally mixed upon transport in fast-moving air masses that passed through the Beijing area in about one day. In contrast, the aerosols of the 880 nm group were characterized by high sulfate concentrations, and seemed to be internally mixed during slow transport over the Yellow Sea region over approximately 2 to 4 days. The absorption and scattering coefficients of the 880 nm group were noticeably higher compared to those of the 370 nm group. The average absorption ångström exponent (AAE) was estimated to be 1.29 and 1.0 for the 370 and 880 nm groups, respectively, in the range 370-950 nm. These results demonstrated that the optical properties of aerosols were intimately linked to chemical composition and mixing state, characteristics determined both by source and atmospheric aging processes. In OC dominant aerosols, absorption was enhanced in the UV region, which was possibly due to refractory and pyrolized OC compounds. Under sulfate dominant conditions, the sulfate coating on BC particles likely contributed to the absorption of the longer visible light. Consequently, single scattering albedo (SSA) was higher for the 880 nm group than for the 370 nm group, emphasizing that the relative abundances of absorbing and scattering constituents are also important in estimating the climate effect of aerosols.

The differential contributions of pFC and temporo-parietal cortex to multimodal semantic control: exploring refractory effects in semantic aphasia.

PubMed

Gardner, Hannah E; Lambon Ralph, Matthew A; Dodds, Naomi; Jones, Theresa; Ehsan, Sheeba; Jefferies, Elizabeth

2012-04-01

Aphasic patients with multimodal semantic impairment following pFC or temporo-parietal (TP) cortex damage (semantic aphasia [SA]) have deficits characterized by poor control of semantic activation/retrieval, as opposed to loss of semantic knowledge per se. In line with this, SA patients show "refractory effects"; that is, declining accuracy in cyclical word-picture matching tasks when semantically related sets are presented rapidly and repeatedly. This is argued to follow a build-up of competition between targets and distractors. However, the link between poor semantic control and refractory effects is still controversial for two reasons. (1) Some theories propose that refractory effects are specific to verbal or auditory tasks, yet SA patients show poor control over semantic processing in both word and picture semantic tasks. (2) SA can result from lesions to either the left pFC or TP cortex, yet previous work suggests that refractory effects are specifically linked to the left inferior frontal cortex. For the first time, verbal, visual, and nonverbal auditory refractory effects were explored in nine SA patients who had pFC (pFC+) or TP cortex (TP-only) lesions. In all modalities, patient accuracy declined significantly over repetitions. This refractory effect at the group level was driven by pFC+ patients and was not shown by individuals with TP-only lesions. These findings support the theory that SA patients have reduced control over multimodal semantic retrieval and, additionally, suggest there may be functional specialization within the posterior versus pFC elements of the semantic control network.

Enhancing biomethanogenic treatment of fresh incineration leachate using single chambered microbial electrolysis cells.

PubMed

Gao, Yan; Sun, Dezhi; Dang, Yan; Lei, Yuqing; Ji, Jiayang; Lv, Tingwei; Bian, Rui; Xiao, Zhihui; Yan, Liangming; Holmes, Dawn E

2017-05-01

Methanogenic treatment of municipal solid waste (MSW) incineration leachate can be hindered by high concentrations of refractory organic matter and humification of compounds in the leachate. In an attempt to overcome some of these impediments, microbial electrolysis cells (MECs) were incorporated into anaerobic digesters (ADMECs). COD removal efficiencies and methane production were 8.7% and 44.3% higher in ADMECs than in controls, and ADMEC reactors recovered more readily from souring caused by high organic loading rates. The degradation rate of large macromolecules was substantially higher (96% vs 81%) in ADMEC than control effluent, suggesting that MECs stimulated degradation of refractory organic matter and reduced humification. Exoelectrogenic bacteria and microorganisms known to form syntrophic partnerships were enriched in ADMECs. These results show that ADMECs were more effective at treatment of MSW incineration leachate, and should be taken into consideration when designing future treatment facilities. Copyright © 2017 Elsevier Ltd. All rights reserved.

DEVELOPMENT OF DIES FOR EXTRUSION OF COMPLEX SHAPES OF STEEL AND REFRACTORY ALLOYS. Interim Technical Documentary Progress Report to Aeronautical Systems Division for the Period September 16,1962 through December 31, 1962

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

Hunt, J.G.; Jenkins, R.G.; White, A.M.

1963-03-01

A number of ceramics, metallic compounds, and ceramic-metal composites were successfully hot pressed into the shape of die inserts. Steels were extruded through several of these for the purpose of evaluating the materials or to study methods of supporting the die inserts. Refractory metal inserts were also used in similar tests. Hot pressed inserts consisting of 80 vo1% Al/sub 2/O/ sub 3/--10 vol% W and 80 vol% ThO/sub 2/--10 vol% W cracked but did not erode. Sintered molybdenum inserts flowed excessively, whereas sintered tungsten inserts flowed to a lesser degree. A hard die casing with a slight shrink fit appearsmore » to be the most satisfactory method of support. (auth)« less

Stabilized Alumina/Ethanol Colloidal Dispersion for Seeding High Temperature Air Flows

NASA Technical Reports Server (NTRS)

Wernet, Judith H.; Wernet, Mark P.

1994-01-01

Seeding air flows with particles to enable measurements of gas velocities via laser anemometry and/or particle image velocimetry techniques can be quite exasperating. The seeding requirements are compounded when high temperature environments are encountered and special care must be used in selecting a refractory seed material. The pH stabilization techniques commonly employed in ceramic processing are used to obtain stable dispersions for generating aerosols of refractory seed material. By adding submicron alumina particles to a preadjusted pH solution of ethanol, a stable dispersion is obtained which when atomized produces a high quality aerosol. Commercial grade alumina powder is used with a moderate size distribution. The technique is not limited to alumina/ethanol and is also demonstrated with an alumina/H2O system. Other ceramic powders in various polar solvents could also be used once the point of zero charge (pH(sub pzc)) of the powder in the solvent has been determined.

Microstructural Constraints on the Formation History of Hibonite in Refractory Inclusions

NASA Technical Reports Server (NTRS)

Han, J.; Koop, L.; Keller, L. P.; Davis, A. M.

2017-01-01

Hibonite is a primary refractory phase occurring in many Ca-Al-rich inclusions (CAIs), typically with spinel and perovskite [1]. Previous mi-crostructural studies of hibonite in CAIs revealed the presence of numerous stacking defects along the (001) plane and correlated non-stoichiometry in hibonite [2,3]. These features are interpreted as complex inter-growths of stoichiometric and Ca-deficient hibonites, as shown by experimental studies of reaction-sintered CaO-Al2O3 compounds [4]. Here, we extend our transmission electron microscope (TEM) studies to hibonite-bearing CAIs in CM chondrites that have been well characterized isotopically [5-7]. In addition, we have undertaken a series of anneal-ing experiments to explore the effect of minor elements (Mg and Ti) on the microstucure of hibonite [8,9,this study]. The results of these experiments are being applied to hibonite in CAIs in order to better understand its formation conditions.

Altered spontaneous brain activity in MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder: A resting-state fMRI study.

PubMed

Zhu, Xi; He, Zhongqiong; Luo, Cheng; Qiu, Xiangmiao; He, Shixu; Peng, Anjiao; Zhang, Lin; Chen, Lei

2018-03-15

To investigate alterations in spontaneous brain activity in MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder using resting-state functional magnetic resonance imaging (RS-fMRI). Eighteen MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder (PDD), 17 MRI-negative refractory temporal lobe epilepsy patients without major depressive disorder (nPDD), and 21 matched healthy controls (HC) were recruited from West China Hospital of SiChuan University from April 2016 to June 2017. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and 17-item Hamilton Depression Rating Scale were employed to confirm the diagnosis of major depressive disorder and assess the severity of depression. All participants underwent RS-fMRI scans using a 3.0T MRI system. MRI data were compared and analyzed using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) to measure spontaneous brain activity. These two methods were both used to evaluate spontaneous cerebral activity. The PDD group showed significantly altered spontaneous brain activity in the bilateral mesial prefrontal cortex, precuneus, angular gyrus, right parahippocampal gyrus, and right temporal pole. Meanwhile, compared with HC, the nPDD group demonstrated altered spontaneous brain activity in the temporal neocortex but no changes in mesial temporal structures. The PDD group showed regional brain activity alterations in the prefrontal-limbic system and dysfunction of the default mode network. The underlying pathophysiology of PDD may be provided for further studies. Copyright © 2018 Elsevier B.V. All rights reserved.

Efficacy and Safety of Complete RAAS Blockade with ALISKIREN in Patients with Refractory Proteinuria Who were already on Combined ACE Inhibitor, ARB, and Aldosterone Antagonist.

PubMed

Panattil, Prabitha; Sreelatha, M

2016-09-01

Proteinuria is always associated with intrinsic kidney disese and is a strong predictor of later development of End Stage Renal Disease (ESRD). As Renin Angiotensin Aldosterone System (RAAS) has a role in mediating proteinuria, inhibitors of this system are renoprotective and patients with refractory proteinuria are put on a combination of these agents. The routinely employed triple blockade of RAAS with Angiotensin Converting Enzyme (ACE) inhibitor, ARB and Aldosterone antagonist has many limitations. Addition of Aliskiren to this combination suppresses the RAAS at the earliest stage and can offset many of these limitations. This study was conducted to assess the safety and efficacy of complete RAAS blockade by the addition of Aliskiren in those patients with refractory proteinuria who were already on triple blockade with ACE inhibitor, ARB and Aldosterone antagonist. This study was conducted in Nephrology Department, Calicut Medical College. A total of 36 patients with refractory proteinuria who were already on ACE inhibitor, ARB and Aldosterone antagonist were divided in to two groups A and B. Group A received Aliskiren in addition to the above combination whereas group B continued the same treatment for 12 weeks. Efficacy of the treatment was assessed by recording 24hr urine protein and safety by S.Creatinine, S.Potassium every 2 weeks of the treatment period. Statistical analysis of the lab values was done using SPSS software. Unpaired t-test, Paired t-test and Chi-square test were done for data analysis. Statistical analysis revealed that addition of Aliskiren to the combination therapy with ACE inhibitor+ ARB+ Aldosterone antagonist offers no advantage. But mean reduction in proteinuria was more with Group A than Group B. There is no statistically significant change in S.Creatinine and S.Potassium at the end of treatment. As proteinuria is a strong risk factor for progression to ESRD, even a mild decrease in proteinuria by treatment is renoprotective. Hence treatment with group A may be considered clinically superior to group B with no alteration in safety and tolerability. But further multicentre studies with larger sample size and dose escalation are required for confirmation.

Biologic therapies for refractory juvenile dermatomyositis: five years of experience of the Childhood Arthritis and Rheumatology Research Alliance in North America.

PubMed

Spencer, C H; Rouster-Stevens, K; Gewanter, H; Syverson, G; Modica, R; Schmidt, K; Emery, H; Wallace, C; Grevich, S; Nanda, K; Zhao, Y D; Shenoi, S; Tarvin, S; Hong, S; Lindsley, C; Weiss, J E; Passo, M; Ede, K; Brown, A; Ardalan, K; Bernal, W; Stoll, M L; Lang, B; Carrasco, R; Agaiar, C; Feller, L; Bukulmez, H; Vehe, R; Kim, H; Schmeling, H; Gerstbacher, D; Hoeltzel, M; Eberhard, B; Sundel, R; Kim, S; Huber, A M; Patwardhan, A

2017-06-13

The prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960's with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from human genes) for inflammatory myositis has been reported. In 2011-2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA). The JDM biologic study group developed a survey on the CARRA member experience using biologics for Juvenile DM utilizing Delphi consensus methods in 2011-2012. The survey was completed online by the CARRA members interested in JDM in 2012. A second survey was similarly developed that provided more opportunity to describe their experiences with biologics in JDM in detail and was completed by CARRA members in Feb 2013. During three CARRA meetings in 2013-2015, nominal group techniques were used for achieving consensus on the current choices of biologic drugs. A final survey was performed at the 2016 CARRA meeting. One hundred and five of a potential 231 pediatric rheumatologists (42%) responded to the first survey in 2012. Thirty-five of 90 had never used a biologic for Juvenile DM at that time. Fifty-five of 91 (denominators vary) had used biologics for JDM in their practice with 32%, 5%, and 4% using rituximab, etanercept, and infliximab, respectively, and 17% having used more than one of the three drugs. Ten percent used a biologic as monotherapy, 19% a biologic in combination with methotrexate (mtx), 52% a biologic in combination with mtx and corticosteroids, 42% a combination of a biologic, mtx, corticosteroids (steroids), and an immunosuppressive drug, and 43% a combination of a biologic, IVIG and mtx. The results of the second survey supported these findings in considerably more detail with multiple combinations of drugs used with biologics and supported the use of rituximab, abatacept, anti-TNFα drugs, and tocilizumab in that order. One hundred percent recommended that CARRA continue studying biologics for JDM. The CARRA meeting survey in 2016 again supported the study and use of these four biologic drug groups. Our CARRA JDM biologic work group developed and performed three surveys demonstrating that pediatric rheumatologists in North America have been using multiple biologics for refractory JDM in numerous scenarios from 2011 to 2016. These survey results and our consensus meetings determined our choice of four biologic therapies (rituximab, abatacept, tocilizumab and anti-TNFα drugs) to consider for refractory JDM treatment when indicated and to evaluate for comparative effectiveness and safety in the future. Significance and Innovations This is the first report that provides a substantial clinical experience of a large group of pediatric rheumatologists with biologics for refractory JDM over five years. This experience with biologic therapies for refractory JDM may aid pediatric rheumatologists in the current treatment of these children and form a basis for further clinical research into the comparative effectiveness and safety of biologics for refractory JDM.

Diaphragmatic Breathing Reduces Belching and Proton Pump Inhibitor Refractory Gastroesophageal Reflux Symptoms.

PubMed

Ong, Andrew Ming-Liang; Chua, Laura Teng-Teng; Khor, Christopher Jen-Lock; Asokkumar, Ravishankar; S/O Namasivayam, Vikneswaran; Wang, Yu-Tien

2018-03-01

In patients with gastroesophageal reflux disease (GERD) and excessive belching, most belches are supragastric, and can induce reflux episodes and worsen GERD. Supragastric belching (SGB) might be reduced with diaphragmatic breathing exercises. We investigated whether diaphragmatic breathing therapy is effective in reducing belching and proton pump inhibitor (PPI)-refractory gastroesophageal reflux symptoms. We performed a prospective study of 36 consecutive patients with GERD refractory to PPI therapy and a belching visual analogue scale (VAS) score of 6 or more, seen at a gastroenterology clinic at a tertiary hospital in Singapore from April 2015 through October 2016. Patients underwent high-resolution manometry and 24-hour pH-impedance studies while they were off PPIs. Fifteen patients were placed on a standardized diaphragmatic breathing exercise protocol (treatment group) and completed questionnaires at baseline, after diaphragmatic breathing therapy, and 4 months after the therapy ended. Twenty-one patients were placed on a waitlist (control subjects), completed the same questionnaires with an additional questionnaire after their waitlist period, and eventually received diaphragmatic breathing therapy. The primary outcome was reduction in belching VAS by 50% or more after treatment. Secondary outcomes included GERD symptoms (evaluated using the reflux disease questionnaire) and quality of life (QoL) scores, determined from the Reflux-Qual Short Form and EuroQoL-VAS. Nine of the 15 patients in the treatment group (60%) and none of the 21 control subjects achieved the primary outcome (P < .001). In the treatment group, the mean belching VAS score decreased from 7.1 ± 1.5 at baseline to 3.5 ± 2.0 after diaphragmatic breathing therapy; in the control group, the mean VAS score was 7.6 ± 1.1 at baseline and 7.4 ± 1.3 after the waitlist period. Eighty percent of patients in the treatment group significantly reduced belching frequency compared with 19% in control subjects (P = .001). Treatment significantly reduced symptoms of GERD (the mean reflux disease questionnaire score decreased by 12.2 in the treatment group and 3.1 in the control group; P = .01). The treatment significantly increased QoL scores (the mean Reflux-Qual Short Form score increased by 15.4 in the treatment group and 5.2 in the control group; P = .04) and mean EuroQoL-VAS scores (15.7 increase in treatment group and 2.4 decrease in the control group). These changes were sustained at 4 months after treatment. In the end, 20 of the 36 patients who received diaphragmatic breathing therapy (55.6%), all with excessive SGB, achieved the primary outcome. In a prospective study, we found a standardized protocol for diaphragmatic breathing to reduce belching and PPI-refractory gastroesophageal reflux symptoms, and increase QoL in patients with PPI-refractory GERD with belching-especially those with excessive SGB. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Efficacy of tolvaptan in patients with refractory ascites in a clinical setting

PubMed Central

Ohki, Takamasa; Sato, Koki; Yamada, Tomoharu; Yamagami, Mari; Ito, Daisaku; Kawanishi, Koki; Kojima, Kentaro; Seki, Michiharu; Toda, Nobuo; Tagawa, Kazumi

2015-01-01

AIM: To elucidate the efficacies of tolvaptan (TLV) as a treatment for refractory ascites compared with conventional treatment. METHODS: We retrospectively enrolled 120 refractory ascites patients between January 1, 2009 and September 31, 2014. Sixty patients were treated with oral TLV at a starting dose of 3.75 mg/d in addition to sodium restriction (> 7 g/d), albumin infusion (10-20 g/wk), and standard diuretic therapy (20-60 mg/d furosemide and 25-50 mg/d spironolactone) and 60 patients with large volume paracentesis in addition to sodium restriction (less than 7 g/d), albumin infusion (10-20 g/wk), and standard diuretic therapy (20-120 mg/d furosemide and 25-150 mg/d spironolactone). Patient demographics and laboratory data, including liver function, were not matched due to the small number of patients. Continuous variables were analyzed by unpaired t-test or paired t-test. Fisher’s exact test was applied in cases comparing two nominal variables. We analyzed factors affecting clinical outcomes using receiver operating characteristic curves and multivariate regression analysis. We also used multivariate Cox’s proportional hazard regression analysis to elucidate the risk factors that contributed to the increased incidence of ascites. RESULTS: TLV was effective in 38 (63.3%) patients. The best cut-off values for urine output and reduced urine osmolality as measures of refractory ascites improvement were > 1800 mL within the first 24 h and > 30%, respectively. Multivariate regression analysis indicated that > 25% reduced urine osmolality [odds ratio (OR) = 20.7; P < 0.01] and positive hepatitis C viral antibodies (OR = 5.93; P = 0.05) were positively correlated with an improvement of refractory ascites, while the total bilirubin level per 1.0 mg/dL (OR = 0.57; P = 0.02) was negatively correlated with improvement. In comparing the TLV group and controls, only the serum sodium level was significantly lower in the TLV group (133 mEq/L vs 136 mEq/L; P = 0.02). However, there were no significant differences in the other parameters between the two groups. The cumulative incidence rate was significantly higher in the control group with a median incidence time of 30 d in the TLV group and 20 d in the control group (P = 0.01). Cox hazard proportional multivariate analysis indicated that the use of TLV (OR = 0.58; P < 0.01), uncontrolled liver neoplasms (OR = 1.92; P < 0.01), total bilirubin level per 1.0 mg/dL (OR = 1.10; P < 0.01), and higher sodium level per 1.0 mEq/L (OR = 0.94; P < 0.01) were independent factors that contributed to incidence. CONCLUSION: Administration of TLV results in better control of refractory ascites and reduced the incidence of additional invasive procedures or hospitalization compared with conventional ascites treatments. PMID:26140088

Effectiveness of Combined Tear Film Therapy in Patients with Evaporative Dry Eye with Short Tear Film Breakup Time.

PubMed

Kim, Yung Hui; Kang, Yeon Soo; Lee, Hyo Seok; Choi, Won; You, In Cheon; Yoon, Kyung Chul

2017-10-01

The aim of this study was to evaluate the effectiveness of combined tear film therapy targeted to aqueous, mucin, and lipid layers in patients with refractory evaporative dry eye (EDE) with short tear film breakup time (TBUT). The patients who had EDE with short TBUT and severe symptoms refractory to artificial tears were treated with hyaluronic acid (HA) 0.15% and diquafosol tetrasodium (DQS) 3% (Group 1), HA and carbomer-based lipid-containing eyedrops (Liposic EDO Gel, LPO) (Group 2), or HA, DQS, and LPO (Group 3). Ocular Surface Disease Index (OSDI) score, visual analog scale (VAS) symptom score, TBUT, Schirmer score, and corneal and conjunctival staining scores were evaluated, and noninvasive tear film breakup time (NIBUT) and tear meniscus height were measured using Keratograph ® 5 M before and 1 and 3 months after treatment. OSDI scores, VAS scores, TBUT, and NIBUT were improved at 1 and 3 months after treatment in all groups (all P < 0.05). At each follow-up visit, the total OSDI, OSDI symptom, and all VAS scores were significantly lower in group 3 compared with groups 1 and 2 (all P < 0.05). In addition, TBUT and NIBUT were significantly higher in group 3 compared with groups 1 and 2 (all P < 0.05). No significant adverse effects were noted in the groups during treatment. Mucin or lipid-targeting agents combined with aqueous supplements in patients with refractory EDE with short TBUT might improve subjective symptoms and TBUT. Of this, targeting whole tear film layers was most effective in improving ocular symptoms and tear film quality.

Atopy: a risk factor of refractory mycoplasma pneumoniae pneumonia?

PubMed

Bao, Yi-Xiao; Li, Jing; Tian, Ye; Liu, Quang-Hua; Bao, Jun

2017-11-01

To investigate the relationship of pathogen DNA copies with clinic and laboratory features among children with Mycoplasma pneumoniae (MP) pneumonia. A total of 95 enrolled children with MP pneumonia were assigned into the high-MP-load group (>10 6 /mL) and the low-MP-load group (≤10 6 /mL) according to MP-DNA copies in bronchoalveolar lavage fluid (BALF). Clinical characteristics and any allergy history were collected. Aeroallergens and food allergens were detected with a skin test. Serum IgE and eosinophil cationic protein (ECP) were assessed using enzyme immunoassay. BALF levels of IL-4, IFN-γ, IL-8 and TNF-α were assessed by ELISA. Compared with the low-MP-load group, 72.7% in the high-MP-load group developed refractory MP pneumonia who failed to respond to at least 1-week treatment with macrolides (72.7% vs 41.9%, P = 0.005). More children in the high-load group than those in the low-load group presented with extrapulmonary manifestations, lung consolidation, pleural effusion and atopic conditions including any allergy history, positive findings of aeroallergen test and increased serum IgE and ECP (P < 0.05). A significant higher BALF IL-4 level was seen in the high-load group versus the low-load group (23.00 ± 11.24 vs 14.68 ± 7.12; pg/mL; P < 0.01). There were no significant differences in BALF levels of IFN-γ, IL-8 and TNF-α between the two groups (P > 0.05). Atopy may be a risk factor for the presence and severity of refractory MP pneumonia due to the high pathogen load in airway. © 2016 John Wiley & Sons Ltd.

Effects and safety of 99Tc-MDP in patients with refractory ankylosing spondylitis: a 2-stage (30-week follow-up) clinical trial.

PubMed

Xu, Yunyun; Zhong, Yi; Zhao, Minjing; Tu, Liudan; Fan, Meida; Zhang, Pingping; Wei, Qiujing; Cao, Shuangyan; Li, Qiuxia; Liao, Zetao; Lin, Zhiming; Pan, Yunfeng; Jin, Ou; Gu, Jieruo

2018-01-01

To evaluate the clinical efficacy and safety in patients with refractory ankylosing spondylitis (AS) initiating 99Tc-MDP therapy and explore the mechanisms. Refractory AS patients were enrolled in the clinical trial and received 99Tc-MDP treatments for 3 or 5 courses according to ASAS improvement. Efficacy and safety evaluations were conducted during the follow-up. 37 cytokines were quantified by Luminex at baseline and week 30. p-values<0.05 were considered statistically significant. 51 refractory AS patients were included, with 20 healthy people serving as the control group. The patients were in an active disease state (mean (SD) ASDAS 3.66 (0.83), BASDAI 4.53 (1.92)), 42(82.35%) patients had syndesmophytes. Their cytokines were significantly higher than that in the control group. After 3 courses of 99Tc-MDP treatment, 32 (62.75%) patients achieved ASAS20 improvement, 24 (47.06%) patients achieved a clinically significant improvement (ΔASDAS-CRP≥1.1). 27 patients entered the second stage to complete 5 courses of the treatment, all of whom achieved ASAS20 improvement, 18 (66.67%) patients achieved a clinically significant improvement. All clinical parameters including ASAS and ASDAS significantly improved as the treatment was continued. Cytokines also had significant down-regulation after the treatment, and the reductions had positive correlations with the improvements of disease activity. No serious adverse event was observed. This investigation confirmed the remarkable efficacy of 99Tc-MDP in a large number of refractory AS patients, and highlighted the mechanism by dramatic regulation on cytokines. 99Tc-MDP was safe in clinical application.

Histomorphological differentiation of non-erosive reflux disease and functional heartburn in patients with PPI-refractory heartburn.

PubMed

Kandulski, A; Jechorek, D; Caro, C; Weigt, J; Wex, T; Mönkemüller, K; Malfertheiner, P

2013-09-01

Proton pump inhibitor (PPI)-refractory heartburn may be due to persistent gastro-oesophageal reflux, oesophageal hypersensitivity or functional heartburn (FH). The differentiation between non-erosive reflux disease (NERD) and FH may be very difficult. However, this differentiation is important for appropriate therapeutic management. Dilated intercellular spaces (DIS), papillary elongation (PE) and basal cell hyperplasia (BCH) can be all assessed by light microscopy. Whether these mucosal abnormalities allow the differentiation of NERD from FH in PPI-refractory patients is uncertain. To assess histopathological findings by light microscopy in patients with refractory heartburn to differentiate NERD from FH. Sixty-two patients with PPI-refractory symptoms underwent EGD and MII-pH after pausing PPI medication for 2 weeks before investigation. Twenty-five subjects without upper gastrointestinal symptoms were included as controls. Symptom assessment was based on the reflux disease questionnaire (RDQ). Biopsies were taken 3-5 cm above the gastro-oesophageal junction. DIS, PE, BCH and infiltration of immune cells were evaluated and a sum score was calculated. Based on endoscopy and MII-pH, GERD was diagnosed in 43 patients (NERD: 20; ERD: 23) and FH in 19 patients. There was no difference in symptoms between the groups. Each individual histopathological item was different between the groups (P < 0.0001). Between NERD and FH, the most significant difference was found for DIS and the histopathological sum score (P < 0.001). These findings suggest that oesophageal biopsies are useful to differentiate NERD from FH. Increased DIS and a histological sum score are the most significant histopathological abnormalities in NERD as compared with FH. © 2013 John Wiley & Sons Ltd.

Platinum Group Coatings for Refractory Metals

DTIC Science & Technology

1984-06-01

temperatures and deposition was very slow. We decided to try iridium hexaflouride, Siridium trichloride hydrate, iridiuw carbonyl and tris-acetyl acetonato...T:*ouu sue. CO. Rhenium Refractory Metals 03 1 d.pRsiý C rg Iridium Coatings 2i 8 bapo i 10. ASSTRACT Won#~.. on mov ofot~sfte.. iad k.dhItfV by b...b q Oxidation resistant coatings of iridium on rhenium substrates have been produced by chemical vapor deposition from an iridium acetyl acetonate

First-in-human response of BCL-2 inhibitor venetoclax in T-cell prolymphocytic leukemia.

PubMed

Boidol, Bernd; Kornauth, Christoph; van der Kouwe, Emiel; Prutsch, Nicole; Kazianka, Lukas; Gültekin, Sinan; Hoermann, Gregor; Mayerhoefer, Marius E; Hopfinger, Georg; Hauswirth, Alexander; Panny, Michael; Aretin, Marie-Bernadette; Hilgarth, Bernadette; Sperr, Wolfgang R; Valent, Peter; Simonitsch-Klupp, Ingrid; Moriggl, Richard; Merkel, Olaf; Kenner, Lukas; Jäger, Ulrich; Kubicek, Stefan; Staber, Philipp B

2017-12-07

T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive T-lymphoid malignancy usually refractory to current treatment strategies and associated with short overall survival. By applying next-generation functional testing of primary patient-derived lymphoma cells using a library of 106 US Food and Drug Administration (FDA)-approved anticancer drugs or compounds currently in clinical development, we set out to identify novel effective treatments for T-PLL patients. We found that the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (ABT-199) demonstrated the strongest T-PLL-specific response when comparing individual ex vivo drug response in 86 patients with refractory hematologic malignancies. Mechanistically, responses to venetoclax correlated with protein expression of BCL-2 but not with expression of the BCL-2 family members myeloid cell leukemia 1 (MCL-1) and BCL-XL in lymphoma cells. BCL-2 expression was inversely correlated with the expression of MCL-1. Based on the ex vivo responses, venetoclax treatment was commenced in 2 late-stage refractory T-PLL patients resulting in clinical responses. Our findings demonstrate first evidence of single-agent activity of venetoclax both ex vivo and in humans, offering a novel agent in T-PLL. © 2017 by The American Society of Hematology.

Compounds Derived from the Bhutanese Daisy, Ajania nubigena, Demonstrate Dual Anthelmintic Activity against Schistosoma mansoni and Trichuris muris.

PubMed

Wangchuk, Phurpa; Pearson, Mark S; Giacomin, Paul R; Becker, Luke; Sotillo, Javier; Pickering, Darren; Smout, Michael J; Loukas, Alex

2016-08-01

Whipworms and blood flukes combined infect almost one billion people in developing countries. Only a handful of anthelmintic drugs are currently available to treat these infections effectively; there is therefore an urgent need for new generations of anthelmintic compounds. Medicinal plants have presented as a viable source of new parasiticides. Ajania nubigena, the Bhutanese daisy, has been used in Bhutanese traditional medicine for treating various diseases and our previous studies revealed that small molecules from this plant have antimalarial properties. Encouraged by these findings, we screened four major compounds isolated from A. nubigena for their anthelmintic properties. Here we studied four major compounds derived from A. nubigena for their anthelmintic properties against the nematode whipworm Trichuris muris and the platyhelminth blood fluke Schistosoma mansoni using the xWORM assay technique. Of four compounds tested, two compounds-luteolin (3) and (3R,6R)-linalool oxide acetate (1)-showed dual anthelmintic activity against S. mansoni (IC50 range = 5.8-36.9 μg/mL) and T. muris (IC50 range = 9.7-20.4 μg/mL). Using scanning electron microscopy, we determined luteolin as the most efficacious compound against both parasites and additionally was found effective against the schistosomula, the infective stage of S. mansoni (IC50 = 13.3 μg/mL). Luteolin induced tegumental damage to S. mansoni and affected the cuticle, bacillary bands and bacillary glands of T. muris. Our in vivo assessment of luteolin (3) against T. muris infection at a single oral dosing of 100 mg/kg, despite being significantly (27.6%) better than the untreated control group, was markedly weaker than mebendazole (93.1%) in reducing the worm burden in mice. Among the four compounds tested, luteolin demonstrated the best broad-spectrum activity against two different helminths-T. muris and S. mansoni-and was effective against juvenile schistosomes, the stage that is refractory to the current gold standard drug, praziquantel. Medicinal chemistry optimisation including cytotoxicity analysis, analogue development and structure-activity relationship studies are warranted and could lead to the identification of more potent chemical entities for the control of parasitic helminths of humans and animals.

Rapid Clozapine Titration in Patients with Treatment Refractory Schizophrenia.

PubMed

Poyraz, Cana Aksoy; Özdemir, Armağan; Sağlam, Nazife Gamze Usta; Turan, Şenol; Poyraz, Burç Çağrı; Tomruk, Nesrin; Duran, Alaattin

2016-06-01

The aim of this study is to evaluate the safety and effectiveness of rapid clozapine titration in patients with schizophrenia in hospital settings. We conducted a retrospective two-center cohort study to compare the safety and effectiveness of clozapine with different titration rates in treatment-refractory patients with schizophrenia. In the first center, clozapine was started at 25-50 mg followed by 50-100 mg as needed every 6 h on day 1, followed by increases of 50-100 mg/day. In the second center, titration was slower; clozapine initiated with 12.5-50 mg on day 1 followed by increases of 25-50 mg/day. The number of days between starting of clozapine until discharge was shorter in the rapid titration group (22.4 ± 8.72 vs 27.0 ± 10.5, p = 0.1). Number of days of total hospital stay were significantly shorter in the rapid titration group (29.6 ± 10.6 vs 41.2 ± 14.8, p = 0.002). Hypotension was more common in the rapid titration group and one patient had suspected myocarditis. Rapid clozapine titration appeared safe and effective. The length of stay following initiation of clozapine was shorter in the rapid-titration group, although this was not statistically significant. However starting clozapine earlier together with rapid titration has significantly shortened the length of hospital stay in patients with treatment refractory schizophrenia.

[Prevention of refractory cough with mediastinal fat to fill the residual cavity after radical systematic mediastinal lymphadenectomy in patients with right lung cancer].

PubMed

Huang, Jia; Luo, Qingquan; Shentu, Yang; Zhao, Xiaojing

2010-10-01

The aim of this study is to analyze the impact on the cough after radical systematic mediastinal lymphadenectomy and prevention of refractory cough with mediastinal fat to fill the residual cavity after radical systematic mediastinal lymphadenectomy. Sixty patients clinically diagnosed of lung cancer were selected according to the adopt standardization, from January 2008 to December 2008. All of the patients were divided into two groups randomly: the filling-fat group and the non-filling-fat group. The surgical information such as operation duration time bleeding volume during operation, post-operation bleeding volume were recorded. After one month, FACT-L and LCQ were completed. There are no remarkably differences between the operation duration time, bleeding volume in operation and 1st postoperation day's drainage volume of the two groups. There's significant difference in the scores of cough at night after taking off the chest tube, as well as in the scores of LCQ after one month and in the scores of last items of FACT-L. Filling the fat of the mediastinal to cover the residual cavity left by completely systematic mediastinal lymphadenectomy can reduce the refractory cough after surgery, and can also improve the quality of the life. It has no effect on the the operation duration time, bleeding volume in operation and 1st post-operation day's drainage volume of the patients.

Sacral Nerve Stimulation for Pediatric Lower Urinary Tract Dysfunction: Development of a Standardized Pathway with Objective Urodynamic Outcomes.

PubMed

Schober, Megan S; Sulkowski, Jason P; Lu, Peter L; Minneci, Peter C; Deans, Katherine J; Teich, Steven; Alpert, Seth A

2015-12-01

We propose that sacral nerve stimulation is a valid adjunctive therapy for refractory pediatric lower urinary tract dysfunction, and that prospective collection of preoperative and postoperative validated questionnaires and urodynamic data in a standardized fashion is beneficial in characterizing patient response. Patients were candidates for sacral nerve stimulation if they had refractory voiding dysfunction and standard treatments had failed. Preoperative evaluation included urodynamic studies, spinal magnetic resonance imaging, and validated bladder and bowel related questionnaires. Children were stratified into 2 groups, ie overactive bladder with or without incontinence (group 1) and detrusor underactivity/urinary retention requiring clean intermittent catheterization (group 2). A staged procedure was used with initial test lead placement, followed by permanent device insertion 2 weeks later if patients demonstrated symptom improvement with test lead. Postoperatively children were followed with questionnaires and at least 1 urodynamic study. A total of 26 children underwent sacral nerve stimulation. Mean patient age was 10.8 years and median followup was 1.2 years. There were 23 patients in group 1 and 4 in group 2 (1 patient was included in both groups). In group 1 voiding dysfunction scores improved significantly, and urodynamic studies revealed a significant decrease in mean number of uninhibited contractions and maximum detrusor pressure during the filling phase. In group 2 there was significant improvement in mean post-void residual. Sacral nerve stimulation is a treatment option that may produce significant improvement in objective and subjective measures of bladder function in children with refractory lower urinary tract dysfunction. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Preparation of Ti3Al intermetallic compound by spark plasma sintering

NASA Astrophysics Data System (ADS)

Ito, Tsutomu; Fukui, Takahiro

2018-04-01

Sintered compacts of single phase Ti3Al intermetallic compound, which have excellent potential as refractory materials, were prepared by spark plasma sintering (SPS). A raw powder of Ti3Al intermetallic compound with an average powder diameter of 176 ± 56 μm was used in this study; this large powder diameter is disadvantageous for sintering because of the small surface area. The samples were prepared at sintering temperatures (Ts) of 1088, 1203, and 1323 K, sintering stresses (σs) of 16, 32, and 48 MPa, and a sintering time (ts) of 10 min. The calculated relative densities based on the apparent density of Ti3Al provided by the supplier were approximately 100% under all sintering conditions. From the experimental results, it was evident that SPS is an effective technique for dense sintering of Ti3Al intermetallic compounds in a short time interval. In this report, the sintering characteristics of Ti3Al intermetallic compacts are briefly discussed and compared with those of pure titanium compacts.

Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions.

PubMed

Hirsch, Lawrence J; Gaspard, Nicolas; van Baalen, Andreas; Nabbout, Rima; Demeret, Sophie; Loddenkemper, Tobias; Navarro, Vincent; Specchio, Nicola; Lagae, Lieven; Rossetti, Andrea O; Hocker, Sara; Gofton, Teneille E; Abend, Nicholas S; Gilmore, Emily J; Hahn, Cecil; Khosravani, Houman; Rosenow, Felix; Trinka, Eugen

2018-04-01

We convened an international group of experts to standardize definitions of New-Onset Refractory Status Epilepticus (NORSE), Febrile Infection-Related Epilepsy Syndrome (FIRES), and related conditions. This was done to enable improved communication for investigators, physicians, families, patients, and other caregivers. Consensus definitions were achieved via email messages, phone calls, an in-person consensus conference, and collaborative manuscript preparation. Panel members were from 8 countries and included adult and pediatric experts in epilepsy, electroencephalography (EEG), and neurocritical care. The proposed consensus definitions are as follows: NORSE is a clinical presentation, not a specific diagnosis, in a patient without active epilepsy or other preexisting relevant neurological disorder, with new onset of refractory status epilepticus without a clear acute or active structural, toxic or metabolic cause. FIRES is a subcategory of NORSE, applicable for all ages, that requires a prior febrile infection starting between 2 weeks and 24 hours prior to onset of refractory status epilepticus, with or without fever at onset of status epilepticus. Proposed consensus definitions are also provided for Infantile Hemiconvulsion-Hemiplegia and Epilepsy syndrome (IHHE) and for prolonged, refractory and super-refractory status epilepticus. This document has been endorsed by the Critical Care EEG Monitoring Research Consortium. We hope these consensus definitions will promote improved communication, permit multicenter research, and ultimately improve understanding and treatment of these conditions. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Metal alloy coatings and methods for applying

DOEpatents

Merz, Martin D.; Knoll, Robert W.

1991-01-01

A method of coating a substrate comprises plasma spraying a prealloyed feed powder onto a substrate, where the prealloyed feed powder comprises a significant amount of an alloy of stainless steel and at least one refractory element selected from the group consisting of titanium, zirconium, hafnium, niobium, tantalum, molybdenum, and tungsten. The plasma spraying of such a feed powder is conducted in an oxygen containing atmosphere and forms an adherent, corrosion resistant, and substantially homogenous metallic refractory alloy coating on the substrate.

The Influence of refractoriness upon comprehension of non-verbal auditory stimuli.

PubMed

Crutch, Sebastian J; Warrington, Elizabeth K

2008-01-01

An investigation of non-verbal auditory comprehension in two patients with global aphasia following stroke is reported. The primary aim of the investigation was to establish whether refractory access disorders can affect non-verbal input modalities. All previous reports of refractoriness, a cognitive syndrome characterized by response inconsistency, sensitivity to temporal factors and insensitivity to item frequency, have involved comprehension tasks which have a verbal component. Two main experiments are described. The first consists of a novel sound-to-picture and sound-to-word matching task in which comprehension of environmental sounds is probed under conditions of semantic relatedness and semantic unrelatedness. In addition to the two stroke patients, the performance of a group of 10 control patients with non-vascular pathology is reported, along with evidence of semantic relatedness effects in sound comprehension. The second experiment examines environmental sound comprehension within a repetitive probing paradigm which affords assessment of the effects of semantic relatedness, response consistency and presentation rate. It is demonstrated that the two stroke patients show a significant increase in error rate across multiple probes of the same set of sound stimuli, indicating the presence of refractoriness within this non-verbal domain. The implications of the results are discussed with reference to our current understanding of the mechanisms of refractoriness.

Eligibility of real-world patients with chemo-refractory, K-RAS wild-type, metastatic colorectal cancer for palliative intent regorafenib monotherapy.

PubMed

Angeles, Arkhjamil; Hung, Wayne; Cheung, Winson Y

2018-06-23

The CORRECT trial demonstrated survival benefits with regorafenib monotherapy in patients with treatment-refractory, metastatic colorectal cancer (mCRC). However, the trial's stringent eligibility criteria for regorafenib may limit its external validity. We aimed to examine treatment attrition rates and eligibility for regorafenib in routine practice. We identified patients at the British Columbia Cancer Agency diagnosed with mCRC who demonstrated disease progression or intolerable toxicity on 2 or more lines of systemic therapy. During the study timeframe, panitumumab and cetuximab were only used in the chemo-refractory setting. Data on clinicopathologic variables and patient outcomes were ascertained and analyzed. Eligibility was determined using the CORRECT trial criteria. A total of 391 patients were identified, among whom only 39% were eligible for regorafenib: 35% in the panitumumab group and 51% in the cetuximab group. The main reasons for ineligibility in all patients were Eastern Cooperative Oncology Group Performance Status (ECOG PS) > 1 (69%), an elevated total bilirubin (21%), and thromboembolic events in the past 6 months (10%). No difference in eligibility for regorafenib was observed between patients previously receiving panitumumab or cetuximab (P = 0.914; 95% CI 0.550-1.951). Kaplan-Meier analyses showed that regorafenib-eligible compared to regorafenib-ineligible patients had an increased median overall survival of 5.3 versus 2.1 months, respectively (P < 0.001). However, Cox proportional hazard analyses showed that only ECOG PS rather than trial eligibility was correlated with outcomes. The strict eligibility criteria disqualify most patients with treatment-refractory mCRC for regorafenib therapy. Future trials should broaden the eligibility criteria to improve external validity.

Ozone-augmented percutaneous discectomy: a novel treatment option for refractory discogenic sciatica.

PubMed

Crockett, M T; Moynagh, M; Long, N; Kilcoyne, A; Dicker, P; Synnott, K; Eustace, S J

2014-12-01

To assess the short and medium-term efficacy and safety of a novel, minimally invasive therapeutic option combining automated percutaneous lumbar discectomy, intradiscal ozone injection, and caudal epidural: ozone-augmented percutaneous discectomy (OPLD). One hundred and forty-seven patients with a clinical and radiological diagnosis of discogenic sciatica who were refractory to initial therapy were included. Fifty patients underwent OPLD whilst 97 underwent a further caudal epidural. Outcomes were evaluated using McNab's score, improvement in visual analogue score (VAS) pain score, and requirement for further intervention. Follow-up occurred at 1 and 6 months, and comparison was made between groups. OPLD achieved successful outcomes in almost three-quarters of patients in the short and medium term. OPLD achieved superior outcomes at 1 and 6 months compared to caudal epidural. There was a reduced requirement for further intervention in the OPLD group. No significant complications occurred in either group. OPLD is a safe and effective treatment for patients with refractory discogenic sciatica in the short and medium term. OPLD has the potential to offer an alternative second-line minimally invasive treatment option that could reduce the requirement for surgery in this patient cohort. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Gamma knife treatment for refractory epilepsy in seizure focus localized by positron emission tomography/CT★

PubMed Central

Bai, Xia; Wang, Xuemei; Wang, Hongwei; Zhao, Shigang; Han, Xiaodong; Hao, Linjun; Wang, Xiangcheng

2012-01-01

A total of 80 patients with refractory epilepsy were recruited from the Inner Mongolia Medical College Affiliated Hospital. The foci of 60% of the patients could be positioned using a combined positron emission tomography/CT imaging modality. Hyper- and hypometabolism foci were examined as part of this study. Patients who had abnormal metabolism in positron emission tomography/CT imaging were divided into intermittent-phase group and the seizure-phase group. The intermittent-phase group was further divided into a single-focus group and a multiple-foci group according to the number of seizure foci detected by imaging. Following gamma knife treatment, seizure frequency was significantly lower in the intermittent-phase group and the seizure-phase group. Wieser’s classification reached Grade I or II in nearly 40% of patients. Seizure frequency was significantly lower following treatment, but Wieser’s classification score was significantly higher in the seizure-phase group compared with the intermittent-phase group. Seizure frequency was significantly lower following treatment in the single-focus group, but Wieser’s classification score was significantly higher in the single-focus group as compared with the multiple-foci group. PMID:25317147

EPI-001, a compound active against castration-resistant prostate cancer, targets transactivation unit 5 of the androgen receptor

PubMed Central

De Mol, Eva; Fenwick, R. Bryn; Phang, Christopher T. W.; Buzón, Victor; Szulc, Elzbieta; de la Fuente, Alex; Escobedo, Albert; García, Jesús; Bertoncini, Carlos W.; Estébanez-Perpiñá, Eva; McEwan, Iain J.; Riera, Antoni; Salvatella, Xavier

2016-01-01

Castration-resistant prostate cancer is the lethal condition suffered by prostate cancer patients that become refractory to androgen deprivation therapy. EPI-001 is a recently identified compound active against this condition that modulates the activity of the androgen receptor, a nuclear receptor that is essential for disease progression. The mechanism by which this compound exerts its inhibitory activity is however not yet fully understood. Here we show, by using high resolution solution nuclear magnetic resonance spectroscopy, that EPI-001 selectively interacts with a partially folded region of the transactivation domain of the androgen receptor, known as transactivation unit 5, that is key for the ability of prostate cells to proliferate in the absence of androgens, a distinctive feature of castration-resistant prostate cancer. Our results can contribute to the development of more potent and less toxic novel androgen receptor antagonists for treating this disease. PMID:27356095

Magnesium compounds

USGS Publications Warehouse

Kramer, D.A.

2007-01-01

Seawater and natural brines accounted for about 52 percent of U.S. magnesium compounds production in 2006. Dead-burned magnesia was produced by Martin Marietta Magnesia Specialties from well brines in Michigan. Caustic-calcined magnesia was recovered from sea-water by Premier Chemicals in Florida; from well brines in Michigan by Martin Marietta and Rohm and Haas; and from magnesite in Nevada by Premier Chemicals. Intrepid Potash-Wendover and Great Salt Lake Minerals recovered magnesium chloride brines from the Great Salt Lake in Utah. Magnesium hydroxide was produced from brucite by Applied Chemical Magnesias in Texas, from seawater by SPI Pharma in Delaware and Premier Chemicals in Florida, and by Martin Marietta and Rohm and Haas from their operations mentioned above. About 59 percent of the magnesium compounds consumed in the United States was used for refractories that are used mainly to line steelmaking furnaces. The remaining 41 percent was consumed in agricultural, chemical, construction, environmental and industrial applications.

Bone marrow mesenchymal stem cells accelerate the hyperglycemic refractory wound healing by inhibiting an excessive inflammatory response.

PubMed

Nan, Wenbin; Xu, Zhihao; Chen, Zhibin; Yuan, Xin; Lin, Juntang; Feng, Huigen; Lian, Jie; Chen, Hongli

2017-05-01

The aim of the present study was to evaluate the healing effect of bone marrow-derived mesenchymal stem cells administered to hyperglycemia model mice with skin wounds, and to explore the underlying mechanism contributing to their effects in promoting refractory wound healing. A full‑thickness skin wound mouse model was established, and refers to a wound of the skin and subcutaneous tissue. The mice were randomly divided into three groups: Blank control group, hyperglycemic group and a hyperglycemic group treated with stem cells. Wound healing was monitored and the wound‑healing rate was determined at 3, 6, 9, and 12 days following trauma. The structure of the organization of new skin tissue was observed by hematoxylin and eosin staining, and expression levels of the inflammatory cytokines interleukin (IL)‑6 and tumor necrosis factor (TNF)‑α were determined from 1 to 6 days following trauma. The wound healing of the hyperglycemic group was slower than that of the blank group, and the hyperglycemic mice treated with stem cells presented faster healing than the hyperglycemia group. The horny layer and granular layer of the skin were thinner and incomplete in the new skin tissue of the hyperglycemic group, whereas the new skin wound tissue basal layer was flat and demonstrated better fusion with the wound edge in the other two groups. The expression of inflammatory cytokines (IL‑6 and TNF‑α) was significantly increased in all three groups, with continuously higher expression in the hyperglycemic group and decreased expression in the other two groups over time. Hyperglycemia refractory wounds are likely related to the excessive expression of inflammatory cytokines surrounding the wound area. Stem cells may be able to alleviate the excessive inflammatory reaction in the wound tissue of hyperglycemic mice, so as to promote wound healing.

Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-13

Advanced Malignant Solid Neoplasm; RB1 Positive; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma

Abobotulinum - a toxin injection in patients with refractory idiopathic detrusor overactivity: injections in detrusor, trigone and bladder neck or prostatic urethra, versus detrusor - only injections

PubMed Central

Emami, Maryam; Shadpour, Pejman; Kashi, Amir H.; Choopani, Masoud; Zeighami, Mohammadreza

2017-01-01

ABSTRACT Purpose: To evaluate if the injections of abobotulinum-A toxin in trigone and bladder neck/prostatic urethra in addition to detrusor provides better symptoms relief and urodynamic findings in patients with idiopathic detrusor overactivity (IDO) refractory to medical treatment. Materials and Methods: A total of 74 patients with IDO refractory to anticholinergics received injections in detrusor, trigone and bladder neck/prostatic urethra (Group A, N=36) versus detrusor only injections (Group B, N=38) of abobotulinum-A toxin. All patients were evaluated by a standard overactive bladder symptom score (OABSS) questionnaire and cystometrography before and 6 weeks after the operation. OABSS questionnaire was also completed 20 weeks after the operation. Results: The magnitude of OABSS reduction from baseline to 6 weeks after operation in groups A and B patients was 13.4±2.2 versus 11.7±2.1 (p=0.001). Cystometry results were similar in both groups except for higher volume at urgent desire to void in Group B patients (p <0.001). The mean±SD change in residual volume in Group A at 6 weeks after the operation was −4.8±28.6mL (p=0.33) compared to 21.3±16.9mL in Group B patients (p <0.001). Conclusions: In patients with IDO, adding trigone, and bladder neck/prostatic urethra as sites of abobotulinum- A toxin injection produces greater reductions in OABSS score and less residual urine volume but a lower volume at urgent desire to void in comparison with detrusor only injections. PMID:28727385

Impact of the International Prognostic Scoring System cytogenetic risk groups on the outcome of patients with primary myelodysplastic syndromes undergoing allogeneic stem cell transplantation from human leukocyte antigen-identical siblings: a retrospective analysis of the European Society for Blood and Marrow Transplantation-Chronic Malignancies Working Party.

PubMed

Onida, Francesco; Brand, Ronald; van Biezen, Anja; Schaap, Michel; von dem Borne, Peter A; Maertens, Johan; Beelen, Dietrich W; Carreras, Enric; Alessandrino, Emilio P; Volin, Liisa; Kuball, Jürgen H E; Figuera, Angela; Sierra, Jorge; Finke, Jürgen; Kröger, Nicolaus; de Witte, Theo

2014-10-01

Acquired chromosomal abnormalities are important prognostic factors in patients with myelodysplastic syndromes treated with supportive care and with disease-modifying therapeutic interventions, including allogeneic hematopoietic stem cell transplantation. To assess the prognostic impact of cytogenetic characteristics after hematopoietic stem cell transplantation accurately, we investigated a homogeneous group of 523 patients with primary myelodysplastic syndromes who have received stem cells from human leukocyte antigen-identical siblings. Overall survival at five years from transplantation in good, intermediate, and poor cytogenetic risk groups according to the International Prognostic Scoring System was 48%, 45% and 30%, respectively (P<0.01). Both the disease status (complete remission vs. not in complete remission) and the morphological classification at transplant in the untreated patients were significantly associated with probability of overall survival and relapse-free survival (P<0.01). The cytogenetic risk groups have no prognostic impact in untreated patients with refractory anemia ± ringed sideroblasts (P=0.90). However, combining the good and intermediate cytogenetic risk groups and comparing them to the poor-risk group showed within the other three disease-status-at-transplant groups a hazard ratio of 1.86 (95%CI: 1.41-2.45). In conclusion, this study shows that, in a large series of patients with primary myelodysplastic syndromes, poor-risk cytogenetics as defined by the standard International Prognostic Scoring System is associated with a relatively poor survival after allogeneic stem cell transplantation from human leukocyte antigen-identical siblings except in patients who are transplanted in refractory anemia/refractory anemia with ringed sideroblasts stage before progression to higher myelodysplastic syndrome stages. Copyright© Ferrata Storti Foundation.

ASSOCIATION OF POTENTIAL CELIAC DISEASE AND REFRACTORY IRON DEFICIENCY ANEMIA IN CHILDREN AND ADOLESCENTS.

PubMed

Shahriari, Mahdi; Honar, Naser; Yousefi, Ali; Javaherizadeh, Hazhir

2018-01-01

Celiac disease is an enteropathy caused by dietary gluten. The combination of serologic, genetic and histologic data has led to description of other categories of this disease. There are a number of patients with iron deficiency anemia (IDA) that do not respond to iron treatment and may be repeated for many times, Therefore, we aimed to investigate celiac disease in this group. In this cross sectional transverse prospective study from August 2011 to February 2013, in a Pediatric care clinic affiliated to Shiraz University of Medical Sciences, 184 children including 92 IDA patients who responded to treatment using iron supplement, 45 non-responding iron deficient patients, and 47 healthy individuals, with the maximum age of 18 years, with written consent from their parents, participated in serologic screening (with Anti-TTG antibody and anti-Endomysial antibody) for celiac disease. Patients with at least one positive serology test underwent multiple mucosal biopsy from bulb and duodenum. Among 184 participants, 19 (10.3%) subjects had positive serologic test for celiac disease, including 13 (28.9%) patients in the group with refractory IDA, 5 (5.4%) patients in the group with treated IDA, and 1 patient in the healthy group. The frequency of positive serologic test in the group with IDA resistant to treatment was prominently higher than the other two groups (P<0.001). Among the patients with positive serologic celiac test who underwent endoscopy and biopsy, no histologic evidence of celiac disease was seen. They were diagnosed as potential celiac disease. Frequency of potential celiac disease in patients with refractory IDA was higher than control the subjects. Therefore, we recommend serologic screening for early detection and minimizing the complications of celiac disease and repeated iron therapy for this group.

Critical Assessment 14: High Entropy Alloys and Their Development as Structural Materials (Postprint)

DTIC Science & Technology

2015-01-01

Mn and Cu or on refractory metals such as V, Cr, Ti, Mo, Nb , Ta, W, Zr and Hf.5,6 The compound forming elements Al and Ti are often added to both...additional properties include environmental resistance , processibil- ity, appearance (for architectural uses) and low cost. Workhardening and solid...be successful, and some work already reports on the corrosion resistance , oxidation behaviour and wear properties of structural HEAs.5 High entropy

Proceeding of US Army Corps of Engineers Workshop on Sediment Oxygen Demand Held in Providence, Rhode Island on 21-22 August 1990.

DTIC Science & Technology

1992-06-01

part, the composition , structure, and mechanisms for formation of the geopolymers is generally not understood (Henrichs, submitted). A possible scheme...unknown. A major process appears to be the incorpora- tion of organic compounds by refractory geopolymers or humic substances. However, for the most... geopolymers (Ertel and Hedges 1983; Rubinsztain et al. 1984; Taguchi and Sampei 1986). Alternative pathways of geopolymerization could involve alteration

A physiological perspective for utility or futility of alcohol-based hand rub gel against nausea-vomiting: is it P-6 acupoint or transnasal aroma?

PubMed

Gupta, Deepak; Mazumdar, Ashish; Stellini, Michael

2014-09-01

Nausea-vomiting is a common and unpleasant phenomenon with numerous underlying mechanisms and pathways that are not always well elucidated. In clinical practice, refractory nausea-vomiting is encountered in several settings. Antiemetic medications may reduce these symptoms but are not always effective in all patients. In the absence of a well-defined optimal strategy for management of nausea-vomiting, the search for better approaches to treat this distressing symptom continues. One of the alternative treatment approaches is a compounded formulation called ABHR gel that is comprised of multiple antiemetic medications and has been shown to be useful for symptomatic relief in some patients with refractory nausea-vomiting. It has been suggested that alternative mechanisms should be explored to explain the perceived efficacy of ABHR gel, because transdermal absorption leading to nil-to-minimal or subtherapeutic blood concentrations of active ingredients does not explain the role of ABHR gel in the treatment of nausea-vomiting. In the current paper, we discuss possible mechanisms that may explain ABHR transdermal gel's efficacy. Compounded ABHR transdermal gel formulation's efficacy in antagonizing nausea-vomiting that has been recently questioned may be explained by alternative mechanisms mediated through the P-6 acupoint stimulation and facial-nasal, cooling-related counterstimulation. © The Author(s) 2013.

Study protocol for a multi-institutional, randomised, double-blinded, placebo-controlled phase III trial investigating additive efficacy of duloxetine for neuropathic cancer pain refractory to opioids and gabapentinoids: the DIRECT study.

PubMed

Matsuoka, Hiromichi; Ishiki, Hiroto; Iwase, Satoru; Koyama, Atsuko; Kawaguchi, Takashi; Kizawa, Yoshiyuki; Morita, Tatsuya; Matsuda, Yoshinobu; Miyaji, Tempei; Ariyoshi, Keisuke; Yamaguchi, Takuhiro

2017-08-28

Management of patients with cancer suffering from neuropathic pain refractory to opioids and gabapentinoids remains an important challenge. Duloxetine is one of the choices after first-line treatment fails. The efficacy of duloxetine has been reported in patients with non-cancer disease and in chemotherapy-induced peripheral neuropathy, but no randomised clinical trials have examined its effects on neuropathic cancer pain refractory to first-line treatment. The objective of this study is to assess the analgesic efficacy of duloxetine in patients suffering from neuropathic cancer pain refractory to opioids and gabapentinoids. A multi-institutional, prospective, randomised, double-blind, placebo-controlled, two-parallel trial is planned. The inclusion criteria are adult patients with cancer suffering from neuropathic cancer pain refractory to opioids and gabapentinoids, patients with a Numerical Rating Scale (NRS) pain score of 4 or higher and patients with a total Hospital Anxiety and Depression Scale score of less than 20. Patients with chemotherapy-induced peripheral neuropathy are excluded. The study will take place at 14 sites across Japan. Participants will be randomised (1:1 allocation ratio) to a duloxetine intervention group or a placebo control group. Evaluations will be made at baseline (T0 randomisation), day 0 (T1), day 3 (T2) and day 10 (T3). The primary endpoint is defined as the difference in NRS score for pain intensity (average over the previous 24 hours) at T3 between the duloxetine and placebo groups. A sample size of 70 patients will be examined between July 2015 and March 2018. Ethics approval was obtained at all participating sites.The results of this study will be submitted for publication in international peer-reviewed journals and the key findings presented at international scientific conferences. UMIN000017647; Pre-results. 2.2, 26 April 2017. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Bio-refractory dissolved organic matter and colorants in cassava distillery wastewater: Characterization, coagulation treatment and mechanisms.

PubMed

Zhang, Ming; Wang, Zhou; Li, Penghui; Zhang, Hua; Xie, Li

2017-07-01

An important portion of organic matter and colorants still remain in the biologically treated distillery wastewater, leaving the dark brown and odorous downstream with the heavy loading of chemical oxygen demand and the potential of forming disinfection byproducts. However, those bio-recalcitrant colorants have not been clearly recognized. The current study investigated the features of the bio-refractory organic matter and colorants in a typical distillery effluent, cassava distillery wastewater; special attention was paid to their change and behaviors in the coagulation treatment following the bio-processes. The wastewater analyses denoted that the fraction of high molecular weight (1-50 kDa and >50 kDa) became predominant after the anaerobic-aerobic processes. Importantly, the lignin breakdown products, melanoidins and lignin phenols were confirmed to be the leading colored components, according to the parallel factor analysis of fluorescence excitation-emission matrixes results. Compared with lignin phenols, the former two types of colorants exhibited stronger bio-refractory activity and resulted in smaller color reduction after the aerobic treatment. Neither advanced oxidation nor adsorption could perform efficiently as post-treatment for decolorization in this study. Nevertheless, high removal of color and dissolved organic matter (∼94.0% and ∼78.3%, respectively) could be achieved by the FeCl 3 -involved coagulation under the optimal conditions. The ferric coagulant was found to preferably interact with the aromatic compounds (such as lignin derivatives) and melanoidins via either surface complexation or electric charge neutralization, or both. The findings presented herein might provide an insight into the evaluation of bio-refractory organic colorants and the Fe(III)-involved decolorization mechanisms of ethanol production wastewaters. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gemcitabine, dexamethasone, and cisplatin (GDP) is an effective and well-tolerated salvage therapy for relapsed/refractory diffuse large B-cell lymphoma and Hodgkin lymphoma.

PubMed

Moccia, Alden A; Hitz, Felicitas; Hoskins, Paul; Klasa, Richard; Power, Maryse M; Savage, Kerry J; Shenkier, Tamara; Shepherd, John D; Slack, Graham W; Song, Kevin W; Gascoyne, Randy D; Connors, Joseph M; Sehn, Laurie H

2017-02-01

The optimal choice of salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) remains unknown. Based on promising results of phase II trials, the preferred salvage regimen in British Columbia since 2002 has been the out-patient regimen, gemcitabine, dexamethasone, and cisplatin (GDP). We conducted a retrospective analysis including all patients with relapsed/refractory DLBCL or HL who received GDP as salvage therapy between September 2002 and June 2010. We identified 235 patients: 152 DLBCL, 83 HL. Overall response rates were 49% and 71% for patients with DLBCL and HL, respectively. Within the transplant-eligible population, 52% of patients with DLBCL and 96% of patients with HL proceeded to stem cell transplantation. The 2-year progression-free survival and overall survival were 21% and 28% in the DLBCL cohort, and 58% and 85% in the HL group. GDP is an effective and well-tolerated out-patient salvage regimen for relapsed/refractory DLBCL and HL.

Stacking Defects in Synthetic and Meteoritic Hibonites: Implications for High-Temperature Processes in the Solar Nebula

NASA Technical Reports Server (NTRS)

Han, J.; Keller, L. P.; Brearley, A. J.; Danielson, L. R.

2016-01-01

Hibonite (CaAl12O19) is a primary, highly refractory phase occurring in many Ca-Al-rich inclusions (CAIs) from different chondrite groups, except CI chondrites. Hibonite is predicted to be one of the earliest minerals to condense during cooling of the solar nebula at higher temperatures than any other major CAI mineral. Therefore, hibonite has great potential to reveal the processes and conditions of the very early, high-temperature stages of the solar nebular evolution. Previous microstructural studies of hibonite in CAIs and their Wark-Lovering (WL) rims showed the presence of numerous stacking defects in hibonite. These defects are interpreted as the modification of the stacking sequences of spinel and Ca-containing blocks within the ideal hexagonal hibonite structure, as shown by experimental studies of reaction-sintered ceramic CaO-Al2O3 compounds. We performed preliminary experiments in the CaO-Al2O3-MgO system to understand the formation processes and conditions of defect-structured hibonite found in meteorites.

Pentobarbital versus thiopental in the treatment of refractory intracranial hypertension in patients with traumatic brain injury: a randomized controlled trial

PubMed Central

Pérez-Bárcena, Jon; Llompart-Pou, Juan A; Homar, Javier; Abadal, Josep M; Raurich, Joan M; Frontera, Guillem; Brell, Marta; Ibáñez, Javier; Ibáñez, Jordi

2008-01-01

Introduction Experimental research has demonstrated that the level of neuroprotection conferred by the various barbiturates is not equal. Until now no controlled studies have been conducted to compare their effectiveness, even though the Brain Trauma Foundation Guidelines recommend that such studies be undertaken. The objectives of the present study were to assess the effectiveness of pentobarbital and thiopental in terms of controlling refractory intracranial hypertension in patients with severe traumatic brain injury, and to evaluate the adverse effects of treatment. Methods This was a prospective, randomized, cohort study comparing two treatments: pentobarbital and thiopental. Patients who had suffered a severe traumatic brain injury (Glasgow Coma Scale score after resuscitation ≤ 8 points or neurological deterioration during the first week after trauma) and with refractory intracranial hypertension (intracranial pressure > 20 mmHg) first-tier measures, in accordance with the Brain Trauma Foundation Guidelines. Results A total of 44 patients (22 in each group) were included over a 5-year period. There were no statistically significant differences in ' baseline characteristics, except for admission computed cranial tomography characteristics, using the Traumatic Coma Data Bank classification. Uncontrollable intracranial pressure occurred in 11 patients (50%) in the thiopental treatment group and in 18 patients (82%) in the pentobarbital group (P = 0.03). Under logistic regression analysis – undertaken in an effort to adjust for the cranial tomography characteristics, which were unfavourable for pentobarbital – thiopental was more effective than pentobarbital in terms of controlling intracranial pressure (odds ratio = 5.1, 95% confidence interval 1.2 to 21.9; P = 0.027). There were no significant differences between the two groups with respect to the incidence of arterial hypotension or infection. Conclusions Thiopental appeared to be more effective than pentobarbital in controlling intracranial hypertension refractory to first-tier measures. These findings should be interpreted with caution because of the imbalance in cranial tomography characteristics and the different dosages employed in the two arms of the study. The incidence of adverse effects was similar in both groups. Trial Registration (Trial registration: US Clinical Trials registry NCT00622570.) PMID:18759980

High temperature barrier coatings for refractory metals

NASA Technical Reports Server (NTRS)

Malone, G. A.; Walech, T.

1995-01-01

Improvements in high temperature oxidation resistant metal coating technology will allow NASA and commercial entities to develop competitive civil space transport and communication systems. The success of investigations completed in this program will have a positive impact on broadening the technology base for high temperature materials. The work reported herein describes processes and procedures for successfully depositing coherent oxidation barrier coatings on refractory metals to prevent degradation under very severe operating environments. Application of the new technology developed is now being utilized in numerous Phase 3 applications through several prominent aerospace firms. Major achievements have included: (1) development of means to deposit thick platinum and rhodium coatings with lower stress and fewer microcracks than could be previously achieved; (2) development of processes to deposit thick adherent coatings of platinum group metals on refractory substrates that remain bonded through high temperature excursions and without need for intermediate coatings (bonding processes unique to specific refractory metals and alloys have been defined; (3) demonstration that useful alloys of refractory and platinum coatings can be made through thermal diffusion means; (4) demonstration that selected barrier coatings on refractory substrates can withstand severe oxidizing environments in the range of 1260 deg and 1760 deg C for long time periods essential to the life requirements of the hardware; and (5) successful application of the processes and procedures to prototype hardware. The results of these studies have been instrumental in improved thermal oxidation barrier coatings for the NASP propulsion system. Other Phase 3 applications currently being exploited include small uncooled thrusters for spacecraft and microsatellite maneuvering systems.

Composites of low-density trialuminides: Particulate and long fiber reinforcements

NASA Technical Reports Server (NTRS)

Kumar, K. S.; Dipietro, M. S.; Brown, S. A.; Whittenberger, J. D.

1992-01-01

An examination of the ternary L1(sub 2) trialuminides, Al66Ti25Mn9, Al67Ti25Cr8, and Al22Ti8Fe3 in compression, bending, and tension revealed that none of these compounds exhibited a desirable balance of strength, ductility, and oxidation resistance. Subsequently, specific quaternary and quinary compositions were cast, homogenized, and isothermally forged. Both, the monolithic material and its particulate reinforced counterparts were examined in compression, three point bend, and tension as a function of temperature, and at high temperatures as a function of strain rate. An alternate approach that was examined in this program to enhance the low temperature damage tolerance of these materials was to incorporate long refractory metal wires in the matrix. In summary, it appears that of the various matrix compositions examined, ternary Al66Ti25Mn9 exhibits the best balance in strength, ductility, and oxidation resistance. Although the idea of refractory metal wire reinforcement is an attractive one, a successful combination remains to be identified.

Activation of concurrent apoptosis and necroptosis by SMAC mimetics for the treatment of refractory and relapsed ALL.

PubMed

McComb, Scott; Aguadé-Gorgorió, Júlia; Harder, Lena; Marovca, Blerim; Cario, Gunnar; Eckert, Cornelia; Schrappe, Martin; Stanulla, Martin; von Stackelberg, Arend; Bourquin, Jean-Pierre; Bornhauser, Beat C

2016-05-18

More precise treatment strategies are urgently needed to decrease toxicity and improve outcomes for treatment-refractory leukemia. We used ex vivo drug response profiling of high-risk, relapsed, or refractory acute lymphoblastic leukemia (ALL) cases and identified a subset with exquisite sensitivity to small-molecule mimetics of the second mitochondria-derived activator of caspases (SMAC) protein. Potent ex vivo activity of the SMAC mimetic (SM) birinapant correlated with marked in vivo antileukemic effects, as indicated by delayed engraftment, decreased leukemia burden, and prolonged survival of xenografted mice. Antileukemic activity was dependent on simultaneous execution of apoptosis and necroptosis, as demonstrated by functional genomic dissection with a multicolored lentiCRISPR approach to simultaneously disrupt multiple genes in patient-derived ALL. SM specifically targeted receptor-interacting protein kinase 1 (RIP1)-dependent death, and CRISPR-mediated disruption of RIP1 completely blocked SM-induced death yet had no impact on the response to standard antileukemic agents. Thus, SM compounds such as birinapant circumvent escape from apoptosis in leukemia by activating a potent dual RIP1-dependent apoptotic and necroptotic cell death, which is not exploited by current therapy. Ex vivo drug activity profiling could provide important functional diagnostic information to identify patients who may benefit from targeted treatment with birinapant in early clinical trials. Copyright © 2016, American Association for the Advancement of Science.

Catchment-fed cyanobacterial blooms in brownified temperate lakes

NASA Astrophysics Data System (ADS)

Senar, O.; Creed, I. F.

2017-12-01

One of the most significant impacts of global atmospheric change is the alteration of hydrological regimes and the associated disruption of hydrological connectivity within watersheds. We show how changes in the frequency, magnitude, and duration of hydrological connectivity and disconnectivity is compromising the capacity of forest soils to store organic carbon, and increasing its export to both aquatic and atmospheric systems. Increases in dissolved organic matter (DOM) loads from forested landscapes to aquatic systems and the shift of the DOM pool to a more refractory mixture of organic compounds, a process known as brownification, alters the physical and chemical characteristics of lake environments. Furthermore, by characterizing the stages of brownification (from low to high concentrations of refractory DOM), we show a shift in the limiting factors for phytoplankton growth from macronutrients (nitrogen -N- and phosphorus -P) to micronutrients (iron -Fe) and light availability. This shift is driven by the low concentrations of DOM supplying N and P in early stages of brownification, to the strong Fe-binding capacity of refractory DOM in brownified lakes. As lakes undergo brownification, cyanobacteria adapted to scavenge Fe from DOM-Fe complexes have a competitive advantage leading to the formation of cyanobacterial blooms. Our findings provide evidence that brownification is a driving force leading to cyanobacterial blooms in lakes on forested landscapes, with expected cascading consequences to lake food webs.

Composition of RF-sputtered refractory compounds determined by X-ray photoelectron spectroscopy

NASA Technical Reports Server (NTRS)

Wheeler, D. R.; Brainard, W. A.

1978-01-01

RF-sputtered coatings of CrB2, MoSi2, Mo2C, TiC, and MoS2 were examined by X-ray photoelectron spectroscopy (XPS). Data on stoichiometry, impurity content, and chemical bonding were obtained. The influences of sputtering target history, deposition time, RF power level, and substrate bias were studied. Significant deviations from stoichiometry and high oxide levels were related to target outgassing. The effect of substrate bias depended on the particular coating material studied.

Studies of Silicon-Refractory Metal Interfaces: Photoemission Study of Interface Formation and Compound Nucleation.

DTIC Science & Technology

1984-10-29

Photoelectron energy analysis was done with Si s states 10--14 eV below E,. For CoSi2 and NiSi2, a commercial double-pass electron energy analyzer . The...Collaborative studies with theorists gave rise to modeling ,f interfaces and calculation of electronic energy states for ordered silicides. (i, ,I... analyzed by a double-pass cylindrical mirror energy A. There is no evidence of Cr outdiffusion into the Au analyzer , and the overall resolution

Synthesis of Refractory Compounds with Gasless Combustion Reactions.

DTIC Science & Technology

1983-09-01

either Al or Mg as the reducing agent. With Al as the reductant, the stoichiometric equation is 2Mo03 + B203 + 6 Al 2MoB + 3 A120 3 Using the methods...r. rr. . . ;. ., .s . , . . o. . - •-~~- ~- . . . .4 calculated to be 267.3 kcal/mole. With Mg as the reductant, the stoichio- metric equation for the...reaction conditions also are assumed for each model. Conservation of energy and heat diffusion equations are applied to a characteristic control volume

Synthesis of refractory materials

DOEpatents

Holt, Joseph B.

1984-01-01

Refractory metal nitrides are synthesized during a self-propagating combustion process utilizing a solid source of nitrogren. For this purpose, a metal azide is employed, preferably NaN.sub.3. The azide is combusted with Mg or Ca, and a metal oxide is selected from Groups III-A, IV-A, III-B, IV-B, or a rare earth metal oxide. The mixture of azide, Ca or Mg and metal oxide is heated to the mixture's ignition temperature. At that temperature the mixture is ignited and undergoes self-sustaining combustion until the starter materials are exhausted, producing the metal nitride.

Materials interactions between the thermoelectric converter and the 5kwe reactor system

NASA Technical Reports Server (NTRS)

Ferry, P. B.

1973-01-01

The integration of a compact thermoelectric converter with a 5-kwe reactor system is described. Material interaction uncertainties study is also presented. This includes degradation of the required austenitic - refractory metal transition joint during operation at high temperatures; loss of corrosion resistance; embrittlement by the presence of hydrogen; and loss of design margin by transport of interstitial elements. Analysis and limited experimental evidence indicate that these potential materials interactions can be adequately controlled. Group 5-2 refractory metals can be utilized without unacceptable adverse effect on system reliability.

OPEC chemotherapy (vincristine, prednisolone, etoposide and chlorambucil) for refractory and recurrent Hodgkin's disease.

PubMed

Barnett, M J; Man, A M; Richards, M A; Waxman, J H; Wrigley, P F; Lister, T A

1987-01-01

Fifteen adults with refractory or recurrent Hodgkin's disease were treated with a combination of: vincristine, prednisolone, etoposide and chlorambucil (OPEC). All had previously received mustine, vinblastine, procarbazine and prednisolone (MVPP) and seven had subsequently been treated with alternative regimens. Responses were achieved in four, but complete remission in only one. Toxicity was considerable and five died of treatment related complications. Only two are alive (one in complete remission) more than three years after therapy. The toxicity of the OPEC regimen outweighed its benefit in this group of poor prognosis patients.

Synthesis of refractory materials

DOEpatents

Holt, J.B.

1983-08-16

Refractory metal nitrides are synthesized during a self-propagating combustion process utilizing a solid source of nitrogen. For this purpose, a metal azide is employed, preferably NaN/sub 3/. The azide is combusted with Mg or Ca, and a metal oxide is selected from Groups III-A, IV-A, III-B, IV-B, or a rare earth metal oxide. The mixture of azide, Ca or Mg and metal oxide is heated to the mixture's ignition temperature. At that temperature the mixture is ignited and undergoes self-sustaining combustion until the starter materials are exhausted, producing the metal nitride.

International reference analysis of outcomes in adults with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia

PubMed Central

Gökbuget, Nicola; Dombret, Hervè; Ribera, Jose-Maria; Fielding, Adele K.; Advani, Anjali; Bassan, Renato; Chia, Victoria; Doubek, Michael; Giebel, Sebastian; Hoelzer, Dieter; Ifrah, Norbert; Katz, Aaron; Kelsh, Michael; Martinelli, Giovanni; Morgades, Mireia; O’Brien, Susan; Rowe, Jacob M.; Stieglmaier, Julia; Wadleigh, Martha; Kantarjian, Hagop

2016-01-01

Adults with relapsed/refractory acute lymphoblastic leukemia have an unfavourable prognosis, which is influenced by disease and patient characteristics. To further evaluate these characteristics, a retrospective analysis of 1,706 adult patients with Ph-negative relapsed/refractory B-precursor acute lymphoblastic leukemia diagnosed between 1990–2013 was conducted using data reflecting the standard of care from 11 study groups and large centers in Europe and the United States. Outcomes included complete remission, overall survival, and realization of stem cell transplantation after salvage treatment. The overall complete remission rate after first salvage was 40%, ranging from 35%–41% across disease status categories (primary refractory, relapsed with or without prior transplant), and was lower after second (21%) and third or greater (11%) salvage. The overall complete remission rate was higher for patients diagnosed from 2005 onward (45%, 95% CI: 39%–50%). One- and three-year survival rates after first, second, and third or greater salvage were 26% and 11%, 18% and 6%, and 15% and 4%, respectively, and rates were 2%–5% higher among patients diagnosed from 2005. Prognostic factors included younger age, longer duration of first remission, and lower white blood cell counts at primary diagnosis. This large dataset can provide detailed reference outcomes for patients with relapsed/refractory Ph-negative B-precursor acute lymphoblastic leukemia. clinicaltrials.gov identifier: 02003612 PMID:27587380

Simultaneous degradation of toxic refractory organic pesticide and bioelectricity generation using a soil microbial fuel cell.

PubMed

Cao, Xian; Song, Hai-Liang; Yu, Chun-Yan; Li, Xian-Ning

2015-01-01

In this study, the soil microbial fuel cells (MFCs) were constructed in the topsoil contaminated with toxic refractory organic pesticide, hexachlorobenzene (HCB). The performance of electricity generation and HCB degradation in the soil-MFCs were investigated. The HCB degradation pathway was analyzed based on the determination of degradation products and intermediates. Experimental results showed that the HCB removal efficiencies in the three groups (soil MFCs group, open circuit control group and no adding anaerobic sludge blank group) were 71.15%, 52.49% and 38.92%, respectively. The highest detected power density was 77.5 mW/m(2) at the external resistance of 1000 Ω. HCB was degraded via the reductive dechlorination pathway in the soil MFC under anaerobic condition. The existence of the anode promoted electrogenic bacteria to provide more electrons to increase the metabolic reactions rates of anaerobic bacteria was the main way which could promote the removal efficiencies of HCB in soil MFC. Copyright © 2015 Elsevier Ltd. All rights reserved.

Oxygen sensitive, refractory oxide composition

DOEpatents

Holcombe, Jr., Cressie E.; Smith, Douglas D.

1976-01-01

Oxide compositions containing niobium pentoxide and an oxide selected from the group consisting of hafnia, titania, and zirconia have electrical conductivity characteristics which vary greatly depending on the oxygen content.

Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study.

PubMed

Ravandi, Farhad; Ritchie, Ellen K; Sayar, Hamid; Lancet, Jeffrey E; Craig, Michael D; Vey, Norbert; Strickland, Stephen A; Schiller, Gary J; Jabbour, Elias; Erba, Harry P; Pigneux, Arnaud; Horst, Heinz-August; Recher, Christian; Klimek, Virginia M; Cortes, Jorge; Roboz, Gail J; Odenike, Olatoyosi; Thomas, Xavier; Havelange, Violaine; Maertens, Johan; Derigs, Hans-Günter; Heuser, Michael; Damon, Lloyd; Powell, Bayard L; Gaidano, Gianluca; Carella, Angelo-Michele; Wei, Andrew; Hogge, Donna; Craig, Adam R; Fox, Judith A; Ward, Renee; Smith, Jennifer A; Acton, Gary; Mehta, Cyrus; Stuart, Robert K; Kantarjian, Hagop M

2015-09-01

Safe and effective treatments are urgently needed for patients with relapsed or refractory acute myeloid leukaemia. We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed or refractory acute myeloid leukaemia. This phase 3, double-blind, placebo-controlled trial was undertaken at 101 international sites. Eligible patients with acute myeloid leukaemia were aged 18 years of age or older and had refractory disease or were in first relapse after one or two cycles of previous induction chemotherapy, including at least one cycle of anthracycline (or anthracenedione) plus cytarabine. Patients were randomly assigned 1:1 to vosaroxin (90 mg/m(2) intravenously on days 1 and 4 in a first cycle; 70 mg/m(2) in subsequent cycles) plus cytarabine (1 g/m(2) intravenously on days 1-5) or placebo plus cytarabine through a central interactive voice system with a permuted block procedure stratified by disease status, age, and geographical location. All participants were masked to treatment assignment. The primary efficacy endpoint was overall survival and the primary safety endpoint was 30-day and 60-day all-cause mortality. Efficacy analyses were done by intention to treat; safety analyses included all treated patients. This study is registered with ClinicalTrials.gov, number NCT01191801. Between Dec 17, 2010, and Sept 25, 2013, 711 patients were randomly assigned to vosaroxin plus cytarabine (n=356) or placebo plus cytarabine (n=355). At the final analysis, median overall survival was 7·5 months (95% CI 6·4-8·5) in the vosaroxin plus cytarabine group and 6·1 months (5·2-7·1) in the placebo plus cytarabine group (hazard ratio 0·87, 95% CI 0·73-1·02; unstratified log-rank p=0·061; stratified p=0·024). A higher proportion of patients achieved complete remission in the vosaroxin plus cytarabine group than in the placebo plus cytarabine group (107 [30%] of 356 patients vs 58 [16%] of 355 patients, p<0·0001). Early mortality was similar between treatment groups (30-day: 28 [8%] of 355 patients in the vosaroxin plus cytarabine group vs 23 [7%] of 350 in the placebo plus cytarabine group; 60-day: 70 [20%] vs 68 [19%]). Treatment-related deaths occurred at any time in 20 (6%) of 355 patients given vosaroxin plus cytarabine and in eight (2%) of 350 patients given placebo plus cytarabine. Treatment-related serious adverse events occurred in 116 (33%) and 58 (17%) patients in each group, respectively. Grade 3 or worse adverse events that were more frequent in the vosaroxin plus cytarabine group than in the placebo plus cytarabine group included febrile neutropenia (167 [47%] vs 117 [33%]), neutropenia (66 [19%] vs 49 [14%]), stomatitis (54 [15%] vs 10 [3%]), hypokalaemia (52 [15%] vs 21 [6%]), bacteraemia (43 [12%] vs 16 [5%]), sepsis (42 [12%] vs 18 [5%]), and pneumonia (39 [11%] vs 26 [7%]). Although there was no significant difference in the primary endpoint between groups, the prespecified secondary analysis stratified by randomisation factors suggests that the addition of vosaroxin to cytarabine might be of clinical benefit to some patients with relapsed or refractory acute myeloid leukaemia. Sunesis Pharmaceuticals. Copyright © 2015 Elsevier Ltd. All rights reserved.

High Voltage Pulsed Radiofrequency for the Treatment of Refractory Neuralgia of the Infraorbital Nerve: A Prospective Double-Blinded Randomized Controlled Study.

PubMed

Luo, Fang; Wang, Tao; Shen, Ying; Meng, Lan; Lu, Jingjing; Ji, Nan

2017-05-01

A recent study showed that 50% of patients who suffered from refractory neuralgia of the infraorbital nerve obtained satisfactory efficacy after pulsed radiofrequency (PRF) treatment. A pilot study showed that increasing the output voltage of PRF significantly improved the efficacy for trigeminal neuralgia; however, whether increasing the output voltage of PRF can improve the treatment outcomes for neuralgia of the infraorbital nerve is unknown. To evaluate the efficacy and safety of high voltage PRF treatment in comparison with standard voltage PRF for neuralgia of the infraorbital nerve. Prospective, single-center, double-blinded, randomized, controlled trial. Beijing Tiantan Hospital, Capital Medical University. A total of 60 patients with refractory neuralgia of the infraorbital nerve were randomly divided into the high voltage PRF group and the standard voltage PRF group to treat their infraorbital nerves. Neither the patients, pain physicians, nor the follow-up evaluators knew the patient group assignments. The primary outcome measure was the one-year response rate. The secondary outcome measures included the time to take effect after PRF, the one-month, 3-month, and 6-month response rates, the relapse rate, and adverse reactions. The intent-to-treat analysis showed that the one-month, 3-month, 6-month, and one-year response rates were all 90% in the high voltage group, which were significantly higher than the rates in the standard voltage group (67% [P < 0.05], 67% [P < 0.05], 63% [P < 0.05], and 60% [P <0.01], respectively). Furthermore, 27% of the patients in the high-voltage group and 13% of the patients in the standard voltage group experienced minor transient (10 - 30 days) numbness in the innervation area after PRF; no other serious adverse reactions were observed in the 2 groups (P > 0.05). We did not investigate the dose-effect relationship between the output voltage and efficacy or the effect of a higher pulse dose on efficacy. This study was a single-center study, and multi-center, randomized, controlled studies are needed to obtain the highest level of empirical evidence. Additionally, the follow-up period lasted only one year in this study; thus, long-term efficacy needs to be further confirmed. The results showed that high voltage PRF was effective and safe for patients with refractory neuralgia of the infraorbital nerve and could become a treatment option in patients who do not respond to conservative treatment.

NCCN Guidelines Insights: Non-Hodgkin's Lymphomas, Version 3.2016.

PubMed

Horwitz, Steven M; Zelenetz, Andrew D; Gordon, Leo I; Wierda, William G; Abramson, Jeremy S; Advani, Ranjana H; Andreadis, C Babis; Bartlett, Nancy; Byrd, John C; Fayad, Luis E; Fisher, Richard I; Glenn, Martha J; Habermann, Thomas M; Lee Harris, Nancy; Hernandez-Ilizaliturri, Francisco; Hoppe, Richard T; Kaminski, Mark S; Kelsey, Christopher R; Kim, Youn H; Krivacic, Susan; LaCasce, Ann S; Lunning, Matthew; Nademanee, Auayporn; Press, Oliver; Rabinovitch, Rachel; Reddy, Nishitha; Reid, Erin; Roberts, Kenneth; Saad, Ayman A; Sokol, Lubomir; Swinnen, Lode J; Vose, Julie M; Yahalom, Joachim; Zafar, Nadeem; Dwyer, Mary; Sundar, Hema; Porcu, Pierluigi

2016-09-01

Peripheral T-cell lymphomas (PTCLs) represent a relatively uncommon heterogeneous group of non-Hodgkin's lymphomas (NHLs) with an aggressive clinical course and poor prognosis. Anthracycline-based multiagent chemotherapy with or without radiation therapy followed by first-line consolidation with high-dose therapy followed by autologous stem cell rescue (HDT/ASCR) is the standard approach to most of the patients with newly diagnosed PTCL. Relapsed or refractory disease is managed with second-line systemic therapy followed by HDT/ASCR or allogeneic stem cell transplant, based on the patient's eligibility for transplant. In recent years, several newer agents have shown significant activity in patients with relapsed or refractory disease across all 4 subtypes of PTCL. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for NHL, specific to the management of patients with relapsed or refractory PTCL. Copyright © 2016 by the National Comprehensive Cancer Network.

Pevonedistat and Ibrutinib in Treating Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia or Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-03-20

B-Cell Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Marginal Zone Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma; Richter Syndrome

Evaluation of a simplified modified Atkins diet for use by parents with low levels of literacy in children with refractory epilepsy: A randomized controlled trial.

PubMed

Sharma, Suvasini; Goel, Shaiphali; Jain, Puneet; Agarwala, Anuja; Aneja, Satinder

2016-11-01

This study was planned to develop and evaluate a simple, easy-to-understand variation of the modified Atkins diet, for use by parents with low levels of literacy in children with refractory epilepsy. This study was conducted in two phases. In the first phase, a simplified version of the modified Atkins diet was developed. In the second phase this was evaluated in children aged 2-14 years who had daily seizures despite the appropriate use of at least two anticonvulsant drugs, in an open-label randomized-controlled-trial. Children were randomized to receive either the simplified modified Atkins diet or no dietary intervention for a period of 3 months with the ongoing anticonvulsant medications being continued unchanged in both the groups. Reduction in seizure frequency was the primary outcome-measure. Data was analyzed using intention to treat approach. Adverse effects were also studied. (Clinical trial identifier NCT0189989). Forty-one children were randomly assigned to the diet-group, and 40 were assigned to the control-group. Two patients discontinued the diet during the study period. The proportion of children with>50% seizure reduction was significantly higher in the diet group as compared to the control group (56.1% vs 7.5%, p<0.0001). The proportion of children with 90% seizure reduction was also higher in the diet group (19.5% vs 2%, p=0.09). Six children in the diet group were seizure free at 3 months compared with two in the control group (p=0.26). At 3 months, 6 children had constipation and 5 had weight loss. A simplified version of the modified Atkins diet was developed for use by parents with low levels literacy. This diet was found to be feasible, efficacious and well tolerated in children with refractory epilepsy. Copyright © 2016 Elsevier B.V. All rights reserved.

Subpial transection surgery for epilepsy.

PubMed

Krishnaiah, Balaji; Ramaratnam, Sridharan; Ranganathan, Lakshmi Narasimhan

2015-12-03

Nearly 30% of patients with epilepsy continue to have seizures in spite of using several antiepileptic drug (AED) regimens. Such patients are regarded as having refractory, or uncontrolled, epilepsy. No definition of uncontrolled, or medically refractory, epilepsy has been universally accepted, but for the purposes of this review, we will consider seizures as drug resistant if they have failed to respond to a minimum of two AEDs. It is believed that early surgical intervention may prevent seizures at a younger age, which, in turn, may improve the intellectual and social status of children. Many types of surgery are available for treatment of refractory epilepsy; one such procedure is known as subpial transection. To determine the benefits and adverse effects of subpial transection for partial-onset seizures and generalised tonic-clonic seizures in children and adults. We searched the Cochrane Epilepsy Group Specialised Register (29 June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; May 2015, Issue 5) and MEDLINE (1946 to 29 June 2015). We imposed no language restrictions. We considered all randomised and quasi-randomised parallel-group studies, whether blinded or non-blinded. Two review authors (BK and SR) independently screened trials identified by the search. The same two review authors planned to independently assess the methodological quality of studies. When studies were identified for inclusion, one review author would have extracted the data, and the other would have verified the data. We found no relevant studies. We found no evidence to support or refute use of subpial transection surgery for patients with medically refractory epilepsy. Well-designed randomised controlled trials are needed to guide clinical practice.

Super-refractory status epilepticus in West China.

PubMed

Tian, L; Li, Y; Xue, X; Wu, M; Liu, F; Hao, X; Zhou, D

2015-07-01

This study aims to determine the general frequency, mortality, and risk factors of super-refractory status epilepticus (SRSE) versus non-refractory status epilepticus (NRSE) and refractory status epilepticus (RSE). This work is a retrospective study. Clinical data of patients who were diagnosed with status epilepticus (SE) in the neurological ward and neuro-intensive care unit of West China Hospital from January 2009 to December 2012 were collected and analyzed. A total of 98 patients were included in the study. The percentages of NRSE, RSE, and SRSE were 67.3%, 20.4%, and 12.2%, respectively. Convulsive SE was the main seizure type among the three groups. The most common cause of NRSE was related to epilepsy (EP). However, 67.7% of SRSE cases were caused by acute encephalitis. Moreover, 47% of SE and 40% of RSE cases had a history of EP, whereas only 8.3% of SRSE cases had such history (P < 0.01). The percentage of patients with STESS ≤2 was lowest in the SRSE group without statistical significance (P > 0.05). The general mortality of SE was 7.1%, whereas that of SRSE was 50%. During follow-up, most SRSE patients who survived have developed symptomatic EP. This study was the first to use the statistical percentage of SRSE. Approximately 12.2% of SE cases will result in SRSE, which is a challenging medical situation for doctors. Patients with first episodes and acute encephalitis were also prone to develop SRSE. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin’s lymphoma responding to prior salvage therapy

PubMed Central

Devillier, Raynier; Coso, Diane; Castagna, Luca; Brenot Rossi, Isabelle; Anastasia, Antonella; Chiti, Arturo; Ivanov, Vadim; Schiano, Jean Marc; Santoro, Armando; Chabannon, Christian; Balzarotti, Monica; Blaise, Didier; Bouabdallah, Reda

2012-01-01

Background High-dose chemotherapy followed by autologous stem cell transplantation is the standard treatment for relapsed and/or refractory Hodgkin’s lymphoma although half of patients relapse after transplantation. Predictive factors, such as relapse within 12 months, Ann-Arbor stage at relapse, and relapse in previously irradiated fields are classically used to identify patients with poor outcome. Recently, 18-fluorodeoxyglucose positron emission tomography has emerged as a new method for providing information to predict outcome. The aim of this study was to confirm the predictive value of positron emission tomography status after salvage therapy and to compare single versus tandem autologous stem cell transplantation in patients with relapsed and/or refractory Hodgkin’s lymphoma. Design and Methods We report a series of 111 consecutive patients with treatment-sensitive relapsed and/or treatment-refractory Hodgkin’s lymphoma who achieved complete (positron emission tomography-negative group) or partial remission (positron emission tomography-positive group) at positron emission tomography evaluation after salvage chemotherapy and who underwent single or tandem autologous stem cell transplantation. Results Five-year overall and progression-free survival rates were 81% and 64%, respectively. There were significant differences in 5-year progression-free survival (79% versus 23%; P<0.001) and 5-year overall survival (90% versus 55%, P=0.001) between the positron emission tomography-negative and -positive groups, respectively. A complete response, as determined by positron emission tomography evaluation, after salvage therapy predicted significantly better 5-year overall survival rates in both intermediate (91% versus 50%; P=0.029) and unfavorable (89% versus 58%; P=0.026) risk subgroup analyses. In the positron emission tomography-positive subgroup, tandem transplantation improved 5-year progression-free survival from 0% (in the single transplantation group) to 43% (P=0.034). Multivariate analysis showed that positron emission tomography status (hazard ratio: 5.26 [2.57–10.73]) and tandem transplantation (hazard ratio: 0.39 [0.19–0.78]) but not risk factors at relapse (hazard ratio: 1.77 [0.80–3.92]) significantly influenced progression-free survival, while only tomography status significantly influenced overall survival (hazard ratio: 4.03 [1.38–11.75]). Conclusions In patients with relapsed/refractory Hodgkin’s lymphoma responding to prior salvage therapy, positron emission tomography response at time of autologous stem cell transplantation favorably influences outcome and enables identification of patients requiring single or tandem transplantation. PMID:22271893

Clinical Outcomes and Quality of Life Following Surgical Treatment for Refractory Epilepsy

PubMed Central

Liu, Shi-Yong; Yang, Xiao-Lin; Chen, Bing; Hou, Zhi; An, Ning; Yang, Mei-Hua; Yang, Hui

2015-01-01

Abstract Surgery for refractory epilepsy is widely used but the efficacy of this treatment for providing a seizure-free outcome and better quality of life remains unclear. This study aimed to update current evidence and to evaluate the effects of surgery on quality of life in patients with refractory epilepsy. A systematic review and meta-analysis of the literature were conducted and selected studies included 2 groups of refractory epilepsy patients, surgical and nonsurgical. The studies were assessed using the Newcastle–Ottawa Scale. The primary outcome was the seizure-free rate. The secondary outcome was quality of life. Adverse events were also reviewed. After screening, a total of 20 studies were selected: 8 were interventional, including 2 randomized controlled trials, and 12 were observational. All of the studies comprised 1959 patients with refractory epilepsy. The seizure-free rates were significantly higher for patients who received surgery compared with the patients who did not; the combined odds ratio was 19.35 (95% CI = 12.10–30.95, P < 0.001). After adjusting for publication bias the combined odds ratio was 10.25 (95% CI = 5.84–18.00). In both the interventional and observational studies, patients treated surgically had a significantly better quality of life compared with the patients not treated surgically. Complications were listed in 3 studies and the rates were similar in surgical and nonsurgical patients. Our meta-analysis found that for patients with refractory epilepsy, surgical treatment appears to provide a much greater likelihood of seizure-free outcome than nonsurgical treatment, although there is a need for more studies, particularly randomized studies, to confirm this conclusion. Based on more limited data, surgical treatment also appeared to provide a better quality of life and did not seem to increase complications. PMID:25674741

High dose phenobarbitone coma in pediatric refractory status epilepticus; a retrospective case record analysis, a proposed protocol and review of literature.

PubMed

Gulati, Sheffali; Sondhi, Vishal; Chakrabarty, Biswaroop; Jauhari, Prashant; Lodha, Rakesh; Sankar, Jhuma

2018-04-01

Ongoing refractory status epilepticus is associated with significant morbidity and mortality. Therapeutic coma induction with midazolam, thiopentone, phenobarbitone or propofol is indicated when conventional antiepileptics fail to abort seizure. Of these, the most extensively studied is midazolam. Amongst the remaining three, phenobarbitone has the most favourable pharmacological profile, but has not been studied adequately, more so in the pediatric age group. The current retrospective case records analysis is an attempt to describe use of phenobarbitone coma in pediatric refractory status epilepticus. Case records of patients, admitted with status epilepticus to the pediatric inpatient services of a tertiary care teaching hospital of North India between January 2014 and December 2016 were reviewed. Those with refractory status epilepticus who failed to respond to midaolam infusion and phenobarbitone coma was used were included for analysis. Overall, 108 children presented in status, of which 34 developed refractory status epilepticus. Of these 34, 21 responded to midazolam infusion and in 13 high dose phenobarbitone coma following a standardised protocol was used. Amongst these 13 (8 males and 5 females, median age 6 years, IQR: 2.5-9.5), 12 responded and 1 succumbed. The median time to clinical seizure resolution and desired electroencephalographic changes post phenobarbitone initiation were 16 (IQR: 12-25) and 72 h (IQR: 48-120) respectively. High dose phenobarbitone appears to be an effective therapeutic modality in pediatric refractory status epilepticus. The current study provides a protocol for its use which can be validated in future studies with larger sample size. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

The use of sirolimus (rapamycin) in the management of refractory inflammatory bowel disease in children.

PubMed

Mutalib, Mohamed; Borrelli, Osvaldo; Blackstock, Sarah; Kiparissi, Fevronia; Elawad, Mamoun; Shah, Neil; Lindley, Keith

2014-12-01

Management of refractory inflammatory bowel disease (IBD) in children is challenging and once response to conventional medical therapy deviates from the expected, options are often limited. Sirolimus is commonly used in post-transplantation management and is used sparsely as rescue therapy in refractory Crohn's disease. In the present study, we report the efficacy of sirolimus as an adjuvant immunosuppressive therapy in a retrospective case review of a selected group of IBD children who were refractory to the conventional treatments. Medical records of children with refractory IBD unresponsive to conventional therapy and started on sirolimus between 2006 and 2012 were retrospectively reviewed. Clinical response, through Pediatric Ulcerative Colitis Activity Index (PUCAI) and Pediatric Crohn's Disease Activity Index (PCDAI), as well as intestinal inflammation, through specific histological scores, was evaluated. The records of 14 patients were analyzed. Eleven of them had ulcerative colitis (UC) and 3 Crohn's disease (CD); mean age at diagnosis was 9.1 years (standard deviation 3.8). Of UC patients, 5 (45%) achieved clinical remission and 2 (18%) showed clinical response. All CD patients went into clinical remission. Mucosal healing was achieved by 5 children (45%) with UC and 2 (67%) with CD patients. One child with ulcerative colitis was weaned off adalimumab, while 2 children with CD were weaned off prednisolone and methotrexate successfully. Our data provide evidence that sirolimus seems to be effective as rescue therapy in a subgroup of children with severe IBD refractory to conventional therapies by inducing both clinical remission and mucosal healing. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Stimulant-Responsive and Stimulant-Refractory Aggressive Behavior Among Children with ADHD

PubMed Central

Blader, Joseph C.; Pliszka, Steven R.; Jensen, Peter S.; Schooler, Nina R.; Kafantaris, Vivian

2010-01-01

OBJECTIVES The objective of this study was to examine factors that are associated with aggression that is responsive versus refractory to individualized optimization of stimulant monotherapy among children with attention-deficit/hyperactivity disorder (ADHD). METHODS Children who were aged 6 to 13 years and had ADHD, either oppositional defiant disorder or conduct disorder, significant aggressive behavior, and a history of insufficient response to stimulants completed an open stimulant monotherapy optimization protocol. Stimulant titration with weekly assessments of behavior and tolerability identified an optimal regimen for each child. Families also received behavioral therapy. Parents completed the Retrospective-Modified Overt Aggression Scale (R-MOAS) at each visit. Children were classified as having stimulant-refractory aggression on the basis of R-MOAS ratings and clinician judgment. Differences that pertained to treatment, demographic, and psychopathology between groups with stimulant monotherapy–responsive and –refractory aggression were evaluated. RESULTS Aggression among 32 (49.3%) of 65 children was reduced sufficiently after stimulant dosage adjustment and behavioral therapy to preclude adjunctive medication. Those who responded to stimulant monotherapy were more likely to benefit from the protocol’s methylphenidate preparation (once-daily, triphasic release), showed a trend for lower average dosages, and received fewer behavioral therapy sessions than did children with stimulant-refractory aggression. Boys, especially those with higher ratings of baseline aggression and of depressive and manic symptoms, more often exhibited stimulant-refractory aggression. CONCLUSIONS Among children whose aggressive behavior develops in the context of ADHD and of oppositional defiant disorder or conduct disorder, and who had insufficient response to previous stimulant treatment in routine clinical care, systematic, well-monitored titration of stimulant monotherapy often culminates in reduced aggression that averts the need for additional agents. PMID:20837589

Hu antigen R (HuR) multimerization contributes to glioma disease progression.

PubMed

Filippova, Natalia; Yang, Xiuhua; Ananthan, Subramaniam; Sorochinsky, Anastasia; Hackney, James R; Gentry, Zachery; Bae, Sejong; King, Peter; Nabors, L Burt

2017-10-13

Among primary brain cancers, gliomas are the most deadly and most refractory to current treatment modalities. Previous reports overwhelmingly support the role of the RNA-binding protein Hu antigen R (HuR) as a positive regulator of glioma disease progression. HuR expression is consistently elevated in tumor tissues, and a cytoplasmic localization appears essential for HuR-dependent oncogenic transformation. Here, we report HuR aggregation (multimerization) in glioma and the analysis of this tumor-specific HuR protein multimerization in clinical brain tumor samples. Using a split luciferase assay, a bioluminescence resonance energy transfer technique, and site-directed mutagenesis, we examined the domains involved in HuR multimerization. Results obtained with the combination of the split HuR luciferase assay with the bioluminescence resonance energy transfer technique suggested that multiple (at least three) HuR molecules come together during HuR multimerization in glioma cells. Using these data, we developed a model of HuR multimerization in glioma cells. We also demonstrate that exposing glioma cells to the HuR inhibitor tanshinone group compound 15,16-dihydrotanshinone-I or to the newly identified compound 5 disrupts HuR multimerization modules and reduces tumor cell survival and proliferation. In summary, our findings provide new insights into HuR multimerization in glioma and highlight possible pharmacological approaches for targeting HuR domains involved in cancer cell-specific multimerization.

Abemaciclib in Children With DIPG or Recurrent/Refractory Solid Tumors

ClinicalTrials.gov

2017-07-14

Diffuse Intrinsic Pontine Glioma; Brain Tumor, Recurrent; Solid Tumor, Recurrent; Neuroblastoma, Recurrent, Refractory; Ewing Sarcoma, Recurrent, Refractory; Rhabdomyosarcoma, Recurrent, Refractory; Osteosarcoma, Recurrent, Refractory; Rhabdoid Tumor, Recurrent, Refractory

Thermophilic Carbon-Sulfur-Bond-Targeted Biodesulfurization

PubMed Central

Konishi, J.; Ishii, Y.; Onaka, T.; Okumura, K.; Suzuki, M.

1997-01-01

Petroleum contains many heterocyclic organosulfur compounds refractory to conventional hydrodesulfurization carried out with chemical catalysts. Among these, dibenzothiophene (DBT) and DBTs bearing alkyl substitutions are representative compounds. Two bacterial strains, which have been identified as Paenibacillus strains and which are capable of efficiently cleaving carbon-sulfur (C--S) bonds in DBT at high temperatures, have been isolated for the first time. Upon attacking DBT and its various methylated derivatives at temperatures up to 60(deg)C, both growing and resting cells of these bacteria can release sulfur atoms as sulfate ions and leave the monohydroxylated hydrocarbon moieties intact. Moreover, when either of these paenibacilli was incubated at 50(deg)C with light gas oil previously processed through hydrodesulfurization, the total sulfur content in the oil phase clearly decreased. PMID:16535672

Application of ESCA to the determination of stoichiometry in sputtered coatings and interface regions

NASA Technical Reports Server (NTRS)

Wheeler, D. R.

1978-01-01

X-ray photoelectron spectroscopy was used to characterize radiofrequency sputter deposited films of several refractory compounds. Both the bulk film properties such as purity and stoichiometry and the character of the interfacial region between the film and substrate were examined. The materials were CrB2, MoS2, Mo2C, and Mo2B5 deposited on 440C steel. It was found that oxygen from the sputtering target was the primary impurity in all cases. Biasing improves the film purity. The effect of biasing on film stoichiometry is different for each compound. Comparison of the interfacial composition with friction data suggests that adhesion of these films is improved if a region of mixed film and iron oxides can be formed.

Day-night differences in the composition and sources of carbonaceous aerosol at a polluted regional background site in the Netherlands

NASA Astrophysics Data System (ADS)

Dusek, Ulrike; Broekema, Elise; Holzinger, Rupert; Röckmann, Thomas; Meijer, Harro

2017-04-01

The origin of carbonaceous aerosol differs during day- and night-time, because emissions from major sources such as traffic, biomass combustion, and secondary organic aerosol formation show a distinct diurnal pattern. Moreover, photochemical processing and evaporation of semi-volatile organic compounds are enhanced during day-time, due to the availability of sunlight and higher temperatures. Assessing day-night differences in sources and chemical composition can give an indication of the importance of local/regional carbon sources and processing, since day-night differences should be averaged out during long-range transport. If local sources dominate, one could expect a strong diurnal variation in the source profile, but if long-range transport dominates the diurnal variation would be much weaker. In this study we measure the isotopic (14C and 13C) and detailed chemical composition of the organic fraction of the aerosol on high volume PM2.5 filter samples that were collected separately during day and night time. Radiocarbon (14C) measurements are used to estimate three main aerosol sources of organic and elemental carbon (OC and EC): Fossil fuel combustion (ff), biomass combustion (bb), and biogenic sources (bio). The detailed chemical and stable isotopic composition are measured at different desorption temperatures from the filter, which separates the more and less refractory organic compounds. The composition of the organic aerosol is measured using an thermal-desporption Proton Transfer Reaction Time-of-Flight Mass Spectrometer (PTR-ToF-MS) method (Holzinger et al, 2010) and the stable isotopic composition is measured using a thermal desorption IRMS method (Dusek et al., 2013). Source apportionment results using 14C show that the contribution of fossil fuel combustion to EC and OC is higher during day-time than during night-time. This is valid for all seasons. During night-time biomass combustion plays a bigger role as a source of carbonaceous aerosol. Even in the summer, when biomass combustion is a small source, its relative contribution increases between 19:00 and 07:00. However, the diurnal changes in source contributions are relatively moderate (e.g., the biomass burning contribution to TC increased from 31% to 43% for the winter sample with the most distinct day-night difference.) This highlights the importance of long-range transport as a source of the carbonaceous aerosol in this region. First results from chemical composition measurements on four of the samples show that the concentration of less refractory organic carbon (desorption temperature up to 200 °C) increases at night-time much more strongly than the concentration of the more refractory carbon. Similarly, the concentration of small organic compounds with m/z < 100 also increases more strongly than heavier compounds. This indicates partitioning of semi-volatile OC as a possible additional night-time source. The chemical composition will be studied in more detail, focusing on diurnal changes in O/C ratios, individual compounds and compound classes, such as hydrocarbons or organic acids. Dusek, U., Meusinger, C., Oyama, B., Ramon, W., de Wilde, P., Holzinger, R., and Röckmann, T.: A thermal desorption system for measuring δ 13 C ratios on organic aerosol, Journal of aerosol science, 66, 72-82, 2013. Holzinger, R., Williams, J., Herrmann, F., Lelieveld, J., Donahue, N., Röckmann, T., 2010. Aerosol analysis using a Thermal-Desorption Proton-Transfer-Reaction Mass Spectrometer (TD-PTR-MS): a new approach to study processing of organic aerosols. Atmospheric chemistry and physics 10, 2257-2267.

Phenobarbital or potassium bromide as an add-on antiepileptic drug for the management of canine idiopathic epilepsy refractory to imepitoin.

PubMed

Royaux, E; Van Ham, L; Broeckx, B J G; Van Soens, I; Gielen, I; Deforce, D; Bhatti, S F M

2017-02-01

Imepitoin has recently been approved in Europe for the management of dogs with idiopathic epilepsy. Currently, there is no evidence-based information available on the efficacy of antiepileptic drugs used as additions to the therapeutic regimen in dogs with idiopathic epilepsy that are not well controlled with imepitoin. The goal of this study was to evaluate the efficacy of phenobarbital or potassium bromide (KBr) as add-on antiepileptic drugs for controlling dogs refractory to a maximum dose of imepitoin (30 mg/kg twice daily). The study was performed as a prospective, randomised, controlled clinical trial. The efficacy of phenobarbital and KBr was evaluated by comparing monthly seizure frequency (MSF), monthly seizure day frequency (MSDF), the presence of cluster seizures during a retrospective 2-month period with a prospective follow-up of 6 months, and the overall responder rate. Twenty-seven dogs were included in the study, 14 dogs in the phenobarbital group and 13 dogs in the KBr group. Both median MSF and MSDF decreased in the phenobarbital group (both P = 0.001) and in the KBr group (P = 0.004 and P = 0.003, respectively). Overall, the number of dogs with cluster seizures decreased (P = 0.0005). The responder rate was 79% vs. 69% in the phenobarbital and KBr groups, respectively. We conclude that phenobarbital or KBr add-on treatment decreases median MSF and MSDF in epileptic dogs refractory to a maximum dose of imepitoin. Combination therapy was generally well tolerated and resulted in an improvement in seizure management in the majority of the dogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Decompressive craniectomy in diffuse traumatic brain injury.

PubMed

Cooper, D James; Rosenfeld, Jeffrey V; Murray, Lynnette; Arabi, Yaseen M; Davies, Andrew R; D'Urso, Paul; Kossmann, Thomas; Ponsford, Jennie; Seppelt, Ian; Reilly, Peter; Wolfe, Rory

2011-04-21

It is unclear whether decompressive craniectomy improves the functional outcome in patients with severe traumatic brain injury and refractory raised intracranial pressure. From December 2002 through April 2010, we randomly assigned 155 adults with severe diffuse traumatic brain injury and intracranial hypertension that was refractory to first-tier therapies to undergo either bifrontotemporoparietal decompressive craniectomy or standard care. The original primary outcome was an unfavorable outcome (a composite of death, vegetative state, or severe disability), as evaluated on the Extended Glasgow Outcome Scale 6 months after the injury. The final primary outcome was the score on the Extended Glasgow Outcome Scale at 6 months. Patients in the craniectomy group, as compared with those in the standard-care group, had less time with intracranial pressures above the treatment threshold (P<0.001), fewer interventions for increased intracranial pressure (P<0.02 for all comparisons), and fewer days in the intensive care unit (ICU) (P<0.001). However, patients undergoing craniectomy had worse scores on the Extended Glasgow Outcome Scale than those receiving standard care (odds ratio for a worse score in the craniectomy group, 1.84; 95% confidence interval [CI], 1.05 to 3.24; P=0.03) and a greater risk of an unfavorable outcome (odds ratio, 2.21; 95% CI, 1.14 to 4.26; P=0.02). Rates of death at 6 months were similar in the craniectomy group (19%) and the standard-care group (18%). In adults with severe diffuse traumatic brain injury and refractory intracranial hypertension, early bifrontotemporoparietal decompressive craniectomy decreased intracranial pressure and the length of stay in the ICU but was associated with more unfavorable outcomes. (Funded by the National Health and Medical Research Council of Australia and others; DECRA Australian Clinical Trials Registry number, ACTRN012605000009617.).

Esophageal Body Motility for Clinical Assessment in Patients with Refractory Gastroesophageal Reflux Symptoms

PubMed Central

Jiang, Liuqin; Ye, Bixing; Wang, Ying; Wang, Meifeng; Lin, Lin

2017-01-01

Background/Aims Little data exists about esophageal body dysmotility and reflux patterns in refractory gastroesophageal reflux disease (RGERD) patients off therapy. We aimed to evaluate effects of esophageal body dysmotility on reflux parameters in RGERD patients by combining impedance-pH monitoring and high-resolution manometry (HRM). Methods We retrospectively reviewed the impedance-pH data and HRM metrics in patients with refractory gastroesophageal reflux symptoms. Impedance-pH monitoring and manometric data were compared between 2 groups: ineffective esophageal motility (IEM) and normal motility. Results Forty-eight patients (30 males, mean age 54.5 years) were included (16 erosive esophagitis, 24 non-erosive reflux disease, and 8 functional heartburn), amongst which 24 subjects showed IEM, and others had normal motility. Number of patients who had a large break in the IEM group was significantly higher than that of normal motility patients. IEM group had more patients with weakly acid reflux and long term acid reflux than the normal group (P = 0.008, P = 0.004, respectively). There was no statistical difference in baseine impedance levels from z4 to z6 between the 2 groups (2911 ± 1160 Ω vs 3604 ± 1232 Ω, 2766 ± 1254 Ω vs 3752 ± 1439 Ω, 2349 ± 1131 Ω vs 3038 ± 1254 Ω, all P > 0.05). Acid exposure time, numbers of long term acid reflux and weakly acid reflux showed strong negative correlation with esophageal body motility and/or lower esophageal sphincter function. Conclusions IEM was associated more with acid exposure, abnormal weakly acid reflux, and long term acid reflux in RGERD patients. These data suggested the role of esophageal body dysmotility in the pathophysiological mechanisms of RGERD patients. PMID:27599539

Esophageal Body Motility for Clinical Assessment in Patients with Refractory Gastroesophageal Reflux Symptoms.

PubMed

Jiang, Liuqin; Ye, Bixing; Wang, Ying; Wang, Meifeng; Lin, Lin

2017-01-30

Little data exists about esophageal body dysmotility and reflux patterns in refractory gastroesophageal reflux disease (RGERD) patients off therapy. We aimed to evaluate effects of esophageal body dysmotility on reflux parameters in RGERD patients by combining impedance-pH monitoring and high-resolution manometry (HRM). We retrospectively reviewed the impedance-pH data and HRM metrics in patients with refractory gastroesophageal reflux symptoms. Impedance-pH monitoring and manometric data were compared between 2 groups: ineffective esophageal motility (IEM) and normal motility. Forty-eight patients (30 males, mean age 54.5 years) were included (16 erosive esophagitis, 24 non-erosive reflux disease, and 8 functional heartburn), amongst which 24 subjects showed IEM, and others had normal motility. Number of patients who had a large break in the IEM group was significantly higher than that of normal motility patients. IEM group had more patients with weakly acid reflux and long term acid reflux than the normal group ( P = 0.008, P = 0.004, respectively). There was no statistical difference in baseine impedance levels from z4 to z6 between the 2 groups (2911 ± 1160 Ω vs 3604 ± 1232 Ω, 2766 ± 1254 Ω vs 3752 ± 1439 Ω, 2349 ± 1131 Ω vs 3038 ± 1254 Ω, all P > 0.05). Acid exposure time, numbers of long term acid reflux and weakly acid reflux showed strong negative correlation with esophageal body motility and/or lower esophageal sphincter function. IEM was associated more with acid exposure, abnormal weakly acid reflux, and long term acid reflux in RGERD patients. These data suggested the role of esophageal body dysmotility in the pathophysiological mechanisms of RGERD patients.

Electrophysiological effects of desflurane in children with Wolff-Parkinson-White syndrome: a randomized crossover study.

PubMed

Hino, H; Oda, Y; Yoshida, Y; Suzuki, T; Shimada, M; Nishikawa, K

2018-02-01

We hypothesized that, compared with propofol, desflurane prolongs the antegrade accessory pathway effective refractory period (APERP) in children undergoing radiofrequency catheter ablation for Wolff-Parkinson-White (WPW) syndrome. In this randomized crossover study, children aged 4.1-16.1 years undergoing radiofrequency catheter ablation for WPW syndrome were randomly divided into four groups according to the concentration of desflurane and anesthetics used in the first and the second electrophysiological studies (EPS). After induction of general anesthesia with propofol and tracheal intubation, they received one of the following regimens: 0.5 minimum alveolar concentration (MAC) desflurane (first EPS) and propofol (second EPS) (Des0.5-Prop group, n = 8); propofol (first EPS) and 0.5 MAC desflurane (second EPS) (Prop-Des0.5 group, n = 9); 1 MAC desflurane (first EPS) and propofol (second EPS) (Des1.0-Prop group, n = 10); propofol (first EPS) and 1 MAC desflurane (second EPS) (Prop-Des1.0 group, n = 9). Radiofrequency catheter ablation was performed upon completion of EPS. Sample size was determined to detect a difference in the APERP. Desflurane at 1.0 MAC significantly prolonged the APERP compared with propofol, but did not affect the sinoatrial conduction time, atrio-His interval or atrioventricular node effective refractory period. Supraventricular tachycardia was induced in all children receiving propofol, but not induced in 1 and 4 children receiving 0.5 MAC and 1.0 MAC desflurane, respectively. Desflurane enhances the refractoriness and may block the electrical conduction of the atrioventricular accessory pathway, and is therefore not suitable for use in children undergoing radiofrequency catheter ablation for WPW syndrome. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Anaerobic digestion and co-digestion of slaughterhouse waste (SHW): influence of heat and pressure pre-treatment in biogas yield.

PubMed

Cuetos, M J; Gómez, X; Otero, M; Morán, A

2010-10-01

Mesophilic anaerobic digestion (34+/-1 degrees C) of pre-treated (for 20 min at 133 degrees C, >3 bar) slaughterhouse waste and its co-digestion with the organic fraction of municipal solid waste (OFMSW) have been assessed. Semi-continuously-fed digesters worked with a hydraulic retention time (HRT) of 36 d and organic loading rates (OLR) of 1.2 and 2.6 kg VS(feed)/m(3)d for digestion and co-digestion, respectively, with a previous acclimatization period in all cases. It was not possible to carry out an efficient treatment of hygienized waste, even less so when OFMSW was added as co-substrate. These digesters presented volatile fatty acids (VFA), long chain fatty acids (LCFA) and fats accumulation, leading to instability and inhibition of the degradation process. The aim of applying a heat and pressure pre-treatment to promote splitting of complex lipids and nitrogen-rich waste into simpler and more biodegradable constituents and to enhance biogas production was not successful. These results indicate that the temperature and the high pressure of the pre-treatment applied favoured the formation of compounds that are refractory to anaerobic digestion. The pre-treated slaughterhouse wastes and the final products of these systems were analyzed by FTIR and TGA. These tools verified the existence of complex nitrogen-containing polymers in the final effluents, confirming the formation of refractory compounds during pre-treatment. (c) 2010 Elsevier Ltd. All rights reserved.

67P/Churyumov-Gerasimenko: a portrait of a primitive Solar System body

NASA Astrophysics Data System (ADS)

Capaccioni, Fabrizio; Arnold, Gabriele; Capria, Maria Teresa; Erard, Stéphane; Filacchione, Gianrico; De Sanctis, Maria Cristina; Bockelee-Morvan, Dominique; Raponi, Andrea; Ciarniello, Mauro; Leyrat, Cedric

2016-07-01

Comets harbour the most pristine material in our solar system in the form of ice, dust, silicates, and refractory organic material with interstellar heritage. The observations of the VIRTIS imaging spectrometer [1] onboard the Rosetta orbiter, have revealed a very complex surface showing varied morphologies related to active processes. Water ice at the surface of the nucleus have been identified in several areas as stable deposit [2] as well as diurnal frost [3] and implications for the evolution of the nucleus have been derived. The reflectance spectra collected across the surface display a low reflectance factor over the whole spectral range [4], two spectral slopes in the visible and near-infrared ranges and a broad absorption band centred at 3.2 μm. These spectral features describe a largely dehydrated surface, rich in organic compounds and opaque minerals [5]. The low albedo of comet 67P/CG is described by a dark refractory polyaromatic carbonaceous component mixed with opaque minerals. A semi-volatile component, consisting of a complex mix of low weight molecular species not volatilized at T~220 K, is likely a major carrier of the 3.2 μm band. COOH in carboxylic acids is the only chemical group that encompasses the broad width of this feature. It appears as a highly plausible candidate along with the NH4+ ion. Photolytic/thermal residues, produced in the laboratory from interstellar ice analogs, are potentially good spectral analogs [6]. [1] Coradini et al., SSRev, 128, 2007; [2] Filacchione et al, Nature, 529, 2016; [3] De Sanctis et al, Nature, 525, 2015; [4] Ciarniello et al, A&A, 583, 2015; [5] Capaccioni et al., Science, 347, 2015; [6] Quirico et al., Icarus, in press

Commentary on "Comparison of abiraterone acetate versus ketoconazole in patients with metastatic castration resistant prostate cancer refractory to docetaxel." Peer A, Gottfried M, Sinibaldi V, Carducci MA, Eisenberger MA, Sella A, Leibowitz-Amit R, Berger R, Keizman D, Department of Oncology, Rambam Medical Center, Haifa, Israel.: Prostate 2014 Apr;74(4):433-40; doi:10.1002/pros.22765. [Epub 2013 Dec 11].

PubMed

Trump, Donald

2016-05-01

Abiraterone, a potent CYP 17 inhibitor, is standard treatment in docetaxel refractory, metastatic castrate resistant prostate cancer (mCRPC). However, in countries where abiraterone has not been approved yet, or for patients who cannot afford it, ketoconazole is used as an alternative CYP 17 inhibitor. Although preclinical data suggests that ketoconazole is a less potent inhibitor of CYP 17, there are limited clinical data comparing both agents. We aimed to compare the clinical effectiveness of abiraterone versus ketoconazole in docetaxel refractory mCRPC. Records from mCRPC patients treated with ketoconazole (international multicenter database, n = 162) were reviewed retrospectively. Twenty-six patients treated post docetaxel were individually matched by clinicopathologic factors to patients treated with abiraterone (national multicenter database, n = 140). We compared the PSA response, biochemical and radiological progression free survival (PFS), and overall survival (OS) between the groups. PFS and OS were determined by Cox regression. The groups were matched by Gleason score, pre-treatment disease extent, ECOG PS, pre-treatment risk category (Keizman, Oncologist 2012). Furthermore, they were balanced regarding other known confounding risk factors. In the groups of abiraterone versus ketoconazole, PSA response was 46% versus 19% (OR 4.3, P = 0.04), median biochemical PFS 7 versus 2 months (HR 1.54, P = 0.02), median radiological PFS 8 versus 2.5 months (HR 1.8, P = 0.043), median OS 19 versus 11 months (HR 0.53, P = 0.79), and treatment interruption d/t severe adverse events 8% (n = 2) versus 31% (n = 8) (OR 0.6, P = 0.023). In docetaxel refractory mCRPC, the outcome of abiraterone treatment may be superior to ketoconazole. Copyright © 2016 Elsevier Inc. All rights reserved.

Risk factors for drainage-requiring ascites after refractory peritonitis in peritoneal dialysis patients.

PubMed

Lee, Cheng-Chia; Tu, Kun-Hua; Chen, Hsiao-Hui; Chang, Ming-Yang; Hung, Cheng-Chieh

2016-10-01

Refractory peritonitis remains a thorny issue for patients with chronic peritoneal dialysis (PD). Shortly after catheter removal, some patients develop persistent peritoneal inflammation and ascites formation, which require percutaneous drainage for symptom relief. Our study aimed at finding the risk factors for this kind of event. A total of 47 PD patients complicated with refractory peritonitis who underwent catheter removal between January 2009 and December 2011 were enrolled in this study. Data were compared between patients with and without the development of symptomatic ascites requiring drainage during hospitalization. Among the 47 refractory peritonitis patients, 15 patients developed symptomatic ascites that needed further drainage shortly after catheter removal during hospitalization. The following factors were associated with an increased risk: longer dialysis duration, higher peritoneal Kt/V urea, and a significant rise in serum C-reactive protein (CRP) level after catheter removal. These patients had a prolonged hospital stay (62 vs 21 days, P < 0.001) and a significantly higher risk of recurrent loculated ascites during subsequent 6 months of follow-up (33.3 vs 6.2 %, P = 0.022) compared with patients who did not develop ascites requiring drainage during hospitalization. A significant portion of patients with refractory PD peritonitis experienced ascites requiring drainage shortly after catheter removal, which led to a prolonged hospitalization. Whether routine drain placement at the time of catheter removal for this high-risk group would be of benefit warrants further prospective studies.

Pressure induced structural phase transition in IB transition metal nitrides compounds

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

Soni, Shubhangi; Kaurav, Netram, E-mail: netramkaurav@yahoo.co.uk; Jain, A.

2015-06-24

Transition metal mononitrides are known as refractory compounds, and they have, relatively, high hardness, brittleness, melting point, and superconducting transition temperature, and they also have interesting optical, electronic, catalytic, and magnetic properties. Evolution of structural properties would be an important step towards realizing the potential technological scenario of this material of class. In the present study, an effective interionic interaction potential (EIOP) is developed to investigate the pressure induced phase transitions in IB transition metal nitrides TMN [TM = Cu, Ag, and Au] compounds. The long range Coulomb, van der Waals (vdW) interaction and the short-range repulsive interaction upto second-neighbormore » ions within the Hafemeister and Flygare approach with modified ionic charge are properly incorporated in the EIOP. The vdW coefficients are computed following the Slater-Kirkwood variational method, as both the ions are polarizable. The estimated value of the phase transition pressure (Pt) and the magnitude of the discontinuity in volume at the transition pressure are consistent as compared to the reported data.« less

Severe neurotoxicity following ingestion of tetraethyl lead.

PubMed

Wills, Brandon K; Christensen, Jason; Mazzoncini, Joe; Miller, Michael

2010-03-01

Organic lead compounds are potent neurotoxins which can result in death even from small exposures. Traditionally, these compounds are found in fuel stabilizers, anti-knock agents, and leaded gasoline. Cases of acute organic lead intoxication have not been reported for several decades. We report a case of a 13-year-old Iraqi male who unintentionally ingested a fuel stabilizer containing 80-90% tetraethyl lead, managed at our combat support hospital. The patient developed severe neurologic symptoms including agitation, hallucinations, weakness, and tremor. These symptoms were refractory to escalating doses of benzodiazepines and ultimately required endotracheal intubation and a propofol infusion. Adjunctive therapies included chelation, baclofen, and nutrition provided through a gastrostomy tube. The patient slowly recovered and was discharged in a wheelchair 20 days after ingestion, still requiring tube feeding. Follow-up at 62 days post-ingestion revealed near-resolution of symptoms with residual slurred speech and slight limp. This case highlights the profound neurotoxic manifestations of acute organic lead compounds.

Neuromodulation for cephalgias

PubMed Central

Rasskazoff, Serge Y.; Slavin, Konstantin V.

2013-01-01

Headaches (cephalgias) are a common reason for patients to seek medical care. There are groups of patients with recurrent headache and craniofacial pain presenting with malignant course of their disease that becomes refractory to pharmacotherapy and other medical management options. Neuromodulation can be a viable treatment modality for at least some of these patients. We review the available evidence related to the use of neuromodulation modalities for the treatment of medically refractory craniofacial pain of different nosology based on the International Classification of Headache Disorders, 2nd edition (ICHD-II) classification. This article also reviews the scientific rationale of neuromodulation application in management of cephalgias. PMID:23682340

Intravenous sotalol decreases transthoracic cardioversion energy requirement for chronic atrial fibrillation in humans: assessment of the electrophysiological effects by biatrial basket electrodes.

PubMed

Lai, L P; Lin, J L; Lien, W P; Tseng, Y Z; Huang, S K

2000-05-01

This study was undertaken to assess the effects of sotalol on the transthoracic cardioversion energy requirement for chronic atrial fibrillation (AF) and on the atrial electrograms during AF recorded by two basket electrodes. The effects of sotalol infusion on transthoracic electrical cardioversion for chronic atrial fibrillation in humans have not been well investigated. We included 18 patients with persistent AF for more than three months. Atrial electrograms were recorded by two basket electrodes positioned in each atrium respectively. Transthoracic cardioversion was performed before and after sotalol 1.5 mg/kg i.v. infusion. In the 14 patients whose AF could be terminated by cardioversion before sotalol infusion, the atrial defibrillation energy was significantly reduced after sotalol infusion (236 +/- 74 jules [J] vs. 186 +/- 77 J; p < 0.01). Atrial fibrillation was refractory to cardioversion in four patients at baseline and was converted to sinus rhythm by cardioversion after sotalol infusion in two of them. We further divided the patients into two groups. Group A consisted of 10 patients in whom the energy requirement was decreased by sotalol while group B consisted of eight patients in whom the energy requirement was not decreased. The mean A-A (atrial local electrogram) intervals during AF were significantly increased after sotalol infusion in both groups, but the increment of A-A interval was significantly larger in group A than it was in group B patients (36 +/- 13 ms vs. 22 +/- 8 ms for the right atrium; 19 +/- 7 ms vs. 9 +/- 7 ms for the left atrium; both p < 0.05). The spatial and temporal dispersions of A-A intervals were not significantly changed after sotalol infusion in both atria in both groups. Sotalol decreases the atrial defibrillation energy requirement by increasing atrial refractoriness but not by decreasing the dispersion of refractoriness.

A Phase 1-2 Multi-Center Study Evaluating Axicabtagene Ciloleucel in Subjects With Refractory Aggressive Non-Hodgkin Lymphoma (ZUMA-1)

ClinicalTrials.gov

2018-06-18

Refractory Diffuse Large B Cell Lymphoma; Refractory Primary Mediastinal B Cell Lymphoma; Refractory Transformed Follicular Lymphoma; Relapsed/Refractory Transplant Ineligible Diffuse Large B Cell Lymphoma; Relapsed/Refractory Transplant Ineligible Primary Mediastinal B Cell Lymphoma; Relapsed/Refractory Transplant Ineligible Transformed Follicular Lymphoma; Relapsed/Refractory Large B Cell Lymphoma Including DLBCL, PMBCL, TFL and HGBCL After Two Systemic Lines of Therapy" in Phase 2 Expanded Cohorts

The effects of adsorbing organic pollutants from super heavy oil wastewater by lignite activated coke.

PubMed

Tong, Kun; Lin, Aiguo; Ji, Guodong; Wang, Dong; Wang, Xinghui

2016-05-05

The adsorption of organic pollutants from super heavy oil wastewater (SHOW) by lignite activated coke (LAC) was investigated. Specifically, the effects of LAC adsorption on pH, BOD5/COD(Cr)(B/C), and the main pollutants before and after adsorption were examined. The removed organic pollutants were characterized by Fourier transform infrared spectroscopy (FTIR), Boehm titrations, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography with organic carbon detection (LC-OCD). FTIR spectra indicated that organic pollutants containing -COOH and -NH2 functional groups were adsorbed from the SHOW. Boehm titrations further demonstrated that carboxyl, phenolic hydroxyl, and lactonic groups on the surface of the LAC increased. GC-MS showed that the removed main organic compounds are difficult to be degraded or extremely toxics to aquatic organisms. According to the results of LC-OCD, 30.37 mg/L of dissolved organic carbons were removed by LAC adsorption. Among these, hydrophobic organic contaminants accounted for 25.03 mg/L. Furthermore, LAC adsorption was found to increase pH and B/C ratio of the SHOW. The mechanisms of adsorption were found to involve between the hydrogen bonding and the functional groups of carboxylic, phenolic, and lactonic on the LAC surface. In summary, all these results demonstrated that LAC adsorption can remove bio-refractory DOCs, which is beneficial for biodegradation. Copyright © 2016. Published by Elsevier B.V.

Targeted ablation of cardiac sympathetic neurons improves ventricular electrical remodelling in a canine model of chronic myocardial infarction.

PubMed

Xiong, Liang; Liu, Yu; Zhou, Mingmin; Wang, Guangji; Quan, Dajun; Shen, Caijie; Shuai, Wei; Kong, Bin; Huang, Congxin; Huang, He

2018-05-31

The purpose of this study was to evaluate the cardiac electrophysiologic effects of targeted ablation of cardiac sympathetic neurons (TACSN) in a canine model of chronic myocardial infarction (MI). Thirty-eight anaesthetized dogs were randomly assigned into the sham-operated, MI, and MI-TACSN groups, respectively. Myocardial infarction-targeted ablation of cardiac sympathetic neuron was induced by injecting cholera toxin B subunit-saporin compound in the left stellate ganglion (LSG). Five weeks after surgery, the cardiac function, heart rate variability (HRV), ventricular electrophysiological parameters, LSG function and neural activity, serum norepinephrine (NE), nerve growth factor (NGF), and brain natriuretic peptide (BNP) levels were measured. Cardiac sympathetic innervation was determined with immunofluorescence staining of growth associated protein-43 (GAP43) and tyrosine hydroxylase (TH). Compared with MI group, TACSN significantly improved HRV, attenuated LSG function and activity, prolonged corrected QT interval, decreased Tpeak-Tend interval, prolonged ventricular effective refractory period (ERP), and action potential duration (APD), decreased the slopes of APD restitution curves, suppressed the APD alternans, increased ventricular fibrillation threshold, and reduced serum NE, NGF, and BNP levels. Moreover, the densities of GAP43 and TH-positive nerve fibres in the infarcted border zone in the MI-TACSN group were lower than those in the MI group. Targeted ablation of cardiac sympathetic neuron attenuates sympathetic remodelling and improves ventricular electrical remodelling in the chronic phase of MI. These data suggest that TACSN may be a novel approach to treating ventricular arrhythmias.

The efficacy of a multidisciplinary group program for patients with refractory chronic pain

PubMed Central

Inoue, Masayuki; Inoue, Shinsuke; Ikemoto, Tatsunori; Arai, Young-Chang P; Nakata, Masatoshi; Miyazaki, Atsuko; Nishihara, Makoto; Kawai, Takashi; Hatakeyama, Noboru; Yamaguchi, Setsuko; Shimo, Kazuhiro; Miyagawa, Hirofumi; Hasegawa, Tomomi; Sakurai, Hiroki; Hasegawa, Yoshinobu; Ohmichi, Yusuke; Ushida, Takahiro

2014-01-01

BACKGROUND: Chronic pain is a major problem because it can result in not only a reduction in activities of daily living and quality of life but also requires initiation of social assistance. Seeking only to eliminate pain itself would appear to be too narrow an objective, in addition to often being unachievable; therefore, a multifaceted, comprehensive approach with multiple objectives is needed. OBJECTIVE: To describe the effects of a program (the ‘Chronic Pain Class’) offering cognitive behavioural therapy to small groups of individuals with refractory chronic pain in Japan. Exercise was an important feature of the program. METHODS: A total of 46 patients who were experiencing treatment difficulties and decreased activity participated in the program. The programs were conducted in groups of five to seven patients who met weekly for nine weeks. Weekly sessions, which were approximately 2 h in duration, combined lectures with exercise. Several measures related to pain and physical function were administered at the beginning and the conclusion of the program. RESULTS: Nine patients dropped out during the program. A number of measures (eg, pain intensity, disability, catastrophizing thoughts) showed significant improvements after intervention (P<0.002 after Bonferroni correction). Furthermore, most measures of physical function showed substantial improvement, especially seated forward bends, zig-zag walking, self-care and 6 min walk test (P<0.001). CONCLUSION: The results of the present study provide evidence that a combination of cognitive behavioural therapy and exercise should be recommended to patients with refractory chronic pain. PMID:24992454

Nonselective Beta-Blockers Do Not Affect Survival in Cirrhotic Patients with Ascites.

PubMed

Facciorusso, Antonio; Roy, Sunil; Livadas, Sarantis; Fevrier-Paul, Adwalia; Wekesa, Clara; Kilic, Ismail Dogu; Chaurasia, Amit Kumar; Sadeq, Mina; Muscatiello, Nicola

2018-05-03

The role of nonselective beta-blockers in cirrhotic patients with ascites has been recently questioned; however, definitive evidence in this regard is still lacking. To analyze published data on the influence of nonselective beta-blockers as compared to control group on survival of cirrhotic patients with ascites. Computerized bibliographic search on the main databases was performed. Hazard ratios from Kaplan-Meier curves were extracted in order to perform an unbiased comparison of survival estimates. Secondary outcomes were mortality in patients with refractory ascites, pooled rate of nonselective beta-blockers interruption, spontaneous bacterial peritonitis and hepato-renal syndrome incidence. Three randomized controlled trials and 13 observational studies with 8279 patients were included. Overall survival was comparable between the two groups (hazard ratio = 0.86, 0.71-1.03, p = 0.11). Study design resulted as the main source of heterogeneity in sensitivity analysis and meta-regression. Mortality in refractory ascites patients was similar in the two groups (odds ratio = 0.90, 0.45-1.79; p = 0.76). No difference in spontaneous bacterial peritonitis (odds ratio = 0.78, 0.47-1.29, p = 0.33) and hepato-renal syndrome incidence (odds ratio = 1.22, 0.48-3.09; p = 0.67) was observed. Pooled rate of nonselective beta-blockers interruption was 18.6% (5.2-32.1%). Based on our findings, nonselective beta-blockers should not be routinely withheld in patients with cirrhosis and ascites, even if refractory.

iTRAQ-based Quantitative Proteomics Study in Patients with Refractory Mycoplasma pneumoniae Pneumonia.

PubMed

Yu, Jia-Lu; Song, Qi-Fang; Xie, Zhi-Wei; Jiang, Wen-Hui; Chen, Jia-Hui; Fan, Hui-Feng; Xie, Ya-Ping; Lu, Gen

2017-09-25

Mycoplasma pneumoniae (MP) is a leading cause of community-acquired pneumonia in children and young adults. Although MP pneumonia is usually benign and self-limited, in some cases it can develop into life-threating refractory MP pneumonia (RMPP). However, the pathogenesis of RMPP is poorly understood. The identification and characterization of proteins related to RMPP could provide a proof of principle to facilitate appropriate diagnostic and therapeutic strategies for treating paients with MP. In this study, we used a quantitative proteomic technique (iTRAQ) to analyze MP-related proteins in serum samples from 5 patients with RMPP, 5 patients with non-refractory MP pneumonia (NRMPP), and 5 healthy children. Functional classification, sub-cellular localization, and protein interaction network analysis were carried out based on protein annotation through evolutionary relationship (PANTHER) and Cytoscape analysis. A total of 260 differentially expressed proteins were identified in the RMPP and NRMPP groups. Compared to the control group, the NRMPP and RMPP groups showed 134 (70 up-regulated and 64 down-regulated) and 126 (63 up-regulated and 63 down-regulated) differentially expressed proteins, respectively. The complex functional classification and protein interaction network of the identified proteins reflected the complex pathogenesis of RMPP. Our study provides the first comprehensive proteome map of RMPP-related proteins from MP pneumonia. These profiles may be useful as part of a diagnostic panel, and the identified proteins provide new insights into the pathological mechanisms underlying RMPP.

Heart Rate, Responsiveness to Intravenous Immunoglobulin, and Coronary Artery Aneurysms in Kawasaki Disease.

PubMed

Miyakoshi, Chisato; Yamamoto, Yosuke; Yamakawa, Masaru; Fukuhara, Shunichi

2018-05-21

To evaluate whether heart rate (HR) was associated with intravenous immunoglobulin (IVIG) responsiveness or development of coronary artery lesions (CALs) in patients with Kawasaki disease. We conducted a retrospective cohort study using data from in patients with Kawasaki disease who were hospitalized in our institution from 2006 to 2016. The patients were divided into 5 groups according to the age- and temperature-adjusted HR z score (HRZ age/temp ) just before IVIG administration. The ORs of outcomes were estimated by using logistic regression models, with the middle group set as the reference. Of the 322 patients, a total of 98 patients (30%) were refractory to initial IVIG treatment. The patients whose HRZ age/temp belonged to the lowest group were at the highest risk of being refractory to the initial IVIG treatment (OR 2.10 [95% CI 1.01-4.37]). Multivariable analyses showed the same trend, though this was not statistically significant. The patients with the highest HRZ age/temp were most likely to develop CALs (OR 2.61 [95%CI 0.86-7.92]). In patients with Kawasaki disease , HRs has a different relationship with IVIG responsiveness and CALs. Low HRZ age/temp might be associated with high risk of being refractory to the initial IVIG treatment, while the risk of developing CALs increased among those whose HRs were high. Further studies are necessary to investigate the mechanisms regarding HR and these outcomes in Kawasaki disease . Copyright © 2018 Elsevier Inc. All rights reserved.

Ice chemistry on outer solar system bodies: Carboxylic acids, nitriles, and urea detected in refractory residues produced from the UV photolysis of N{sub 2}:CH{sub 4}:CO-containing ices

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

Materese, Christopher K.; Cruikshank, Dale P.; Sandford, Scott A.

Radiation processing of the surface ices of outer solar system bodies may result in the production of new chemical species even at low temperatures. Many of the smaller, more volatile molecules that are likely produced by the photolysis of these ices have been well characterized by laboratory experiments. However, the more complex refractory material formed in these experiments remains largely uncharacterized. In this work, we present a series of laboratory experiments in which low-temperature (15-20 K) N{sub 2}:CH{sub 4}:CO ices in relative proportions 100:1:1 are subjected to UV irradiation, and the resulting materials are studied with a variety of analyticalmore » techniques including infrared spectroscopy, X-ray absorption near-edge structure spectroscopy, gas chromatography coupled with mass spectrometry, and high-resolution mass spectroscopy. Despite the simplicity of the reactants, these experiments result in the production of a highly complex mixture of molecules from relatively low-mass volatiles (tens of daltons) to high-mass refractory materials (hundreds of daltons). These products include various carboxylic acids, nitriles, and urea, which are also expected to be present on the surface of outer solar system bodies, including Pluto and other transneptunian objects. If these compounds occur in sufficient concentrations in the ices of outer solar system bodies, their characteristic bands may be detectable in the near-infrared spectra of these objects.« less

Void forming pyrolytic carbon coating process

DOEpatents

Beatty, Ronald L.; Cook, Jackie L.

2000-01-01

A pyrolytic carbon coated nuclear fuel particle and method of making it. The fuel particle has a core composed of a refractory compound of an actinide metal. The pyrolytic carbon coating surrounds the core so as to provide a void volume therebetween. The coating has an initial density of no greater than 1.45 grams/cm.sup.3 and an anisotropy factor than 3.0 and a final density upon heat treatment above about 2000.degree. C. of greater than 1.7 grams/cm.sup.3 and an anisotropy factor greater than 5.

The Mars Organic Molecule Analyzer (MOMA) Instrument: Characterization of Organic Material in Martian Sediments

PubMed Central

Goesmann, Fred; Brinckerhoff, William B.; Raulin, François; Danell, Ryan M.; Getty, Stephanie A.; Siljeström, Sandra; Mißbach, Helge; Steininger, Harald; Arevalo, Ricardo D.; Buch, Arnaud; Freissinet, Caroline; Grubisic, Andrej; Meierhenrich, Uwe J.; Pinnick, Veronica T.; Stalport, Fabien; Szopa, Cyril; Vago, Jorge L.; Lindner, Robert; Schulte, Mitchell D.; Brucato, John Robert; Glavin, Daniel P.; Grand, Noel; Li, Xiang; van Amerom, Friso H. W.

2017-01-01

Abstract The Mars Organic Molecule Analyzer (MOMA) instrument onboard the ESA/Roscosmos ExoMars rover (to launch in July, 2020) will analyze volatile and refractory organic compounds in martian surface and subsurface sediments. In this study, we describe the design, current status of development, and analytical capabilities of the instrument. Data acquired on preliminary MOMA flight-like hardware and experimental setups are also presented, illustrating their contribution to the overall science return of the mission. Key Words: Mars—Mass spectrometry—Life detection—Planetary instrumentation. Astrobiology 17, 655–685.

[Proton pump inhibitors in gastro-oesophageal reflux disease: what is the further step?].

PubMed

Simon, Mireille; Zerbib, Frank

2013-01-01

Optimisation of proton pump inhibitors use may improve reflux symptoms in 20-25% of the patients. Pathological gastro-oesophageal reflux should be documented in a patient with refractory reflux symptoms using upper endoscopy and/or pH testing. While on proton pump inhibitors twice daily, persistent symptoms are not related to gastro-oesophageal refluxdisease(GERD) in 50% of the patients. The new anti-reflux compounds have yet a limited efficacy and side effects that currently limit their development. Copyright © 2012. Published by Elsevier Masson SAS.

Role of altered esophageal intraluminal baseline impedance levels in patients with gatroesophageal reflux disease refractory to proton pump inhibitors

PubMed Central

Jiang, Liuqin; Ye, Bixing; Lin, Lin; Wang, Ying; Wang, Meifeng

2016-01-01

Abstract Numerous studies have investigated utility of esophageal intraluminal baseline impedance levels (BILs) in gastroesophageal reflux disease (GERD). However, effect of BILs in refractory GERD (RGERD) has not been well investigated. The aim of this study is to evaluate role of BILs in RGERD patients. Total 62 subjects with refractory gastroesophageal reflux symptoms underwent 24-hour impedance-pH monitoring and gastroendoscopy. Distal BILs in acid reflux type were significantly lower than those in nonacid reflux type and functional heartburn (FH) group. Distal BILs of reflux esophagitis (RE) patients were lower than those of nonerosive reflux disease (NERD) patients, while there were no statistical significance between 2 groups. Patients with severe esophagitis had lower distal BILs than those with mild esophagitis and NERD patients, and patients with severe esophagitis in acid reflux type had the lowest distal BILs. Distal BILs were significantly negatively correlated with DeMeester score, episodes of acid reflux, and acid exposure time, but no correlated with episodes of nonacid reflux. Characteristics of BILs in RGERD patients were similar with those in GERD patients, but might be more complicated. Evaluating BILs in RGERD patients could achieve a better understanding of pathophysiology in RGERD. PMID:27537561

Survival Benefit of Tolvaptan for Refractory Ascites in Patients with Advanced Cirrhosis.

PubMed

Tajiri, Kazuto; Tokimitsu, Yoshiharu; Ito, Hiroyuki; Atarashi, Yoshinari; Kawai, Kengo; Minemura, Masami; Yasumura, Satoshi; Takahara, Terumi; Shimizu, Yukihiro; Sugiyama, Toshiro

2018-05-31

The study aimed to evaluate the effects of tolvaptan treatment on survival of patients with decompensated liver cirrhosis with refractory ascites. This multicenter, retrospective, observational study included patients with cirrhosis who were treated with tolvaptan for hepatic ascites refractory to conventional diuretics. Patients who could and could not decrease accompanying diuretics within 1 month after tolvaptan administration were defined as the "Decreased" and "Not-decreased" groups, respectively. Median body weight change 1 week after tolvaptan treatment was -1.95 kg, with the 50% of patients experiencing a 2 kg/week reduction. Spot urinary sodium was found to be a better predictor of tolvaptan response than liver function and liver fibrosis markers. Median survival was significantly longer (not reached versus 116 days, p = 0.005) and serum creatinine concentrations 12 weeks after tolvaptan administration significantly lower (0.99 vs. 1.55 mg/dL, p < 0.05) in the Decreased than in the Not-decreased group. Multivariate analysis showed that the presence of viable hepatocellular carcinoma (hazards ratio [HR] 2.14, p = 0.02) and a decrease in diuretics were independently prognostic of survival (HR 0.36, p < 0.01). The maintenance of renal function is essential in enhancing survival of patients with cirrhosis. Doses of diuretics should be adjusted appropriately during tolvaptan treatment. © 2018 S. Karger AG, Basel.

[Effect of imidapril on the effective refractory period and sodium current of ventricular noninfarction zone in healed myocardial infarction].

PubMed

Li, Yang; Niu, Hui-Yan; Liu, Nian; Zhang, Cun-Tai; Lu, Zai-Ying; Wang, Shi-Wen

2005-07-01

To investigate the effects of imidapril (IMI) on effective refractory period (ERP) and sodium current (I(Na)) of myocytes in ventricular noninfarction zone of healed myocardial infarction (HMI) in rabbit models. Rabbits with left coronary artery ligation were prepared and IMI (0.625 mg x kg(-1) x d(-1), 8 weeks) was orally administered. The ERP and sodium current were recorded. The ERP in HMI heart was prolonged. The ERP in IMI group was lower significantly than that of HMI group. The I(Na) density of myocyte in HMI ventricle decreased obviously. V 1/2 of steady state inactivation of I(Na) shifted to hyperpolarization, and time constant (tau) of recovery from inactivation in HMI ventricular myocyte was longer than that of sham ventricular myocyte. I(Na) density in IMI group increased markedly as compared with that of HMI group. IMI was shown to reverse the abnormal prolongation of ERP in rabbit heart with the HMI and increase I(Na) density. It may be the mechanism of IMI preventing against antiarrhythmia in healed myocardical infarction.

Nivolumab in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma

ClinicalTrials.gov

2018-04-27

Blastic Plasmacytoid Dendritic Cell Neoplasm; Hepatosplenic T-Cell Lymphoma; HTLV-1 Infection; NK-Cell Lymphoma, Unclassifiable; Primary Systemic Anaplastic Large Cell Lymphoma, ALK-Negative; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Angioimmunoblastic T-cell Lymphoma; Recurrent Enteropathy-Associated T-Cell Lymphoma; Recurrent Mycosis Fungoides; Refractory Adult T-Cell Leukemia/Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Angioimmunoblastic T-cell Lymphoma; Refractory Enteropathy-Associated T-Cell Lymphoma; Refractory Mycosis Fungoides; Refractory Nasal Type Extranodal NK/T-Cell Lymphoma; Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified

VSV-hIFNbeta-NIS in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, or T-cell Lymphoma

ClinicalTrials.gov

2018-03-12

Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Angioimmunoblastic T-cell Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Plasma Cell Myeloma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Angioimmunoblastic T-cell Lymphoma; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified; Refractory Plasma Cell Myeloma; Refractory T-Cell Non-Hodgkin Lymphoma

Alisertib and Romidepsin in Treating Patients With Relapsed or Refractory B-Cell or T-Cell Lymphomas

ClinicalTrials.gov

2018-05-02

High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; MYC Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

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.

Intercellular communication within the rat anterior pituitary gland. XV. Properties of spontaneous and LHRH-induced Ca2+ transients in the transitional zone of the rat anterior pituitary in situ.

PubMed

Hattori, Kazuki; Shirasawa, Nobuyuki; Suzuki, Hikaru; Otsuka, Takanobu; Wada, Ikuo; Yashiro, Takashi; Herbert, Damon C; Soji, Tsuyoshi; Hashitani, Hikaru

2013-01-01

In the transitional zone of the rat anterior pituitary, spontaneous and LHRH-induced Ca(2+) dynamics were visualized using fluo-4 fluorescence Ca(2+) imaging. A majority of cells exhibited spontaneous Ca(2+) transients, while small populations of cells remained quiescent. Approximately 70% of spontaneously active cells generated fast, oscillatory Ca(2+) transients that were inhibited by cyclopiazonic acid (10 μm) but not nicardipine (1 μm), suggesting that Ca(2+) handling by endoplasmic reticulum, but not Ca(2+) influx through voltage-dependent L-type Ca(2+) channels, plays a fundamental role in their generation. In the adult rat anterior pituitary, LHRH (100 μg/ml) caused a transient increase in the Ca(2+) level in a majority of preparations taken from the morning group rats killed between 0930 h and 1030 h. However, the second application of LHRH invariably failed to elevate Ca(2+) levels, suggesting that the long-lasting refractoriness to LHRH stimulation was developed upon the first challenge of LHRH. In contrast, LHRH had no effect in most preparations taken from the afternoon group rats euthanized between 1200 h and 1400 h. In the neonatal rat anterior pituitary, LHRH caused a suppression of spontaneous Ca(2+) transients. Strikingly, the second application of LHRH was capable of reproducing the suppression of Ca(2+) signals, indicating that the refractoriness to LHRH had not been established in neonatal rats. These results suggest that responsiveness to LHRH has a long-term refractoriness in adult rats, and that the physiological LHRH surge may be clocked in the morning. Moreover, LHRH-induced excitation and associated refractoriness appear to be incomplete in neonatal rats and may be acquired during development.

Subpial transection surgery for epilepsy.

PubMed

Krishnaiah, Balaji; Ramaratnam, Sridharan; Ranganathan, Lakshmi Narasimhan

2013-08-20

Nearly 30% of patients with epilepsy continue to have seizures in spite of several antiepileptic drug (AED) regimens. In such cases they are regarded as having refractory, or uncontrolled epilepsy.There is no universally accepted definition for uncontrolled or medically refractory epilepsy, but for the purpose of this review, we will consider seizures to be drug resistant if they failed to respond to a minimum of two AEDs. It is believed that early surgical intervention may prevent seizures at a younger age and improve the intellectual and social status of children. There are many types of surgery for refractory epilepsy with subpial transection being one. Our main aim is to determine the benefits and adverse effects of subpial transection for partial-onset seizures and generalised tonic-clonic seizures in children and adults. We searched the Cochrane Epilepsy Group Specialised Register (8 August 2013), The Cochrane Central Register of Controlled Trials (CENTRAL Issue 7 of 12, The Cochrane Library July 2013), and MEDLINE (1946 to 8 August 2013). We did not impose any language restrictions. We considered all randomised and quasi-randomised parallel group studies either blinded or non-blinded. Two review authors (BK and SR) independently screened the trials identified by the search. The same two authors planned to independently assess the methodological quality of studies. If studies had been identified for inclusion, one author would have extracted the data and the other would have verified it. No relevant studies were found. There is no evidence to support or refute the use of subpial transection surgery for medically refractory cases of epilepsy. Well designed randomised controlled trials are needed in future to guide clinical practice.

A study of cognitive function in treatment-refractory obsessive-compulsive disorder treated with capsulotomy.

PubMed

Gong, Feilong; Li, Peng; Li, Bin; Zhang, Shizhen; Zhang, Xinjie; Yang, Sen; Liu, Hongbin; Wang, Wei

2018-02-01

OBJECTIVE Anterior capsulotomy (AC) is sometimes used as a last resort for treatment-refractory obsessive-compulsive disorder (OCD). Previous studies assessing neuropsychological outcomes in patients with OCD have identified several forms of cognitive dysfunction that are associated with the disease, but few have focused on changes in cognitive function in OCD patients who have undergone surgery. In the present study, the authors investigated the effects of AC on the cognitive function of patients with treatment-refractory OCD. METHODS The authors selected 14 patients with treatment-refractory OCD who had undergone bilateral AC between 2007 and 2013, 14 nonsurgically treated OCD patients, and 14 healthy control subjects for this study. The 3 groups were matched for sex, age, and education. Several neuropsychological tests, including Similarities and Block Design, which are subsets of the Wechsler Abbreviated Scale of Intelligence; Immediate and Delayed Logical Memory and Immediate and Delayed Visual Reproduction, which are subsets of the Wechsler Memory Scale-Revised; and Corrects, Categories, Perseverative Errors, Nonperseverative Errors, and Errors, subtests of the Wisconsin Card Sorting Test, were conducted in all 42 subjects at baseline and after AC, after nonsurgical treatment, or at 6-month intervals, as appropriate. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to measure OCD symptoms in all 28 OCD patients. RESULTS The Y-BOCS scores decreased significantly in both OCD groups during the 12-month follow-up period. Surgical patients showed higher levels of improvement in verbal memory, visual memory, visuospatial skills, and executive function than the nonsurgically treated OCD patients. CONCLUSIONS The findings of this study suggest that AC not only reduces OCD symptoms but also attenuates moderate cognitive deficits.

A randomised controlled trial of small particle inhaled steroids in refractory eosinophilic asthma (SPIRA)

PubMed Central

Hodgson, David; Anderson, John; Reynolds, Catherine; Meakin, Garry; Bailey, Helen; Pavord, Ian; Shaw, Dominick; Harrison, Tim

2015-01-01

Background Some patients with refractory asthma have evidence of uncontrolled eosinophilic inflammation in the distal airways. While traditional formulations of inhaled steroids settle predominantly in the large airways, newer formulations with an extra-fine particle size have a more peripheral pattern of deposition. Specifically treating distal airway inflammation may improve asthma control. Methods 30 patients with refractory asthma despite high dose inhaled corticosteroids were identified as having persistent airway eosinophilia. Following 2 weeks of prednisolone 30 mg, patients demonstrating an improvement in asthma control were randomised to receive either ciclesonide 320 µg twice daily or placebo in addition to usual maintenance therapy for 8 weeks. The primary outcome measure was sputum eosinophil count at week 8. Alveolar nitric oxide was measured as a marker of distal airway inflammation. Results There was continued suppression of differential sputum eosinophil counts with ciclesonide (median 2.3%) but not placebo (median 4.5%) though the between-group difference was not significant. When patients who had changed their maintenance prednisolone dose during the trial were excluded the difference between groups was significant (1.4% vs 4.5%, p=0.028). Though alveolar nitric oxide decreased with ciclesonide the value did not reach statistical significance. Conclusions These data demonstrate that patients with ongoing eosinophilic inflammation are not truly refractory, and that suppression of airway eosinophilia may be maintained with additional inhaled corticosteroid. Further work is needed with a focus on patient-orientated outcome measures such as exacerbation rate, with additional tests of small airway function. Trial registration number NCT01171365. Protocol available at http://www.clinicaltrials.gov. PMID:25858909

Rapid clozapine titration in treatment-refractory bipolar disorder.

PubMed

Ifteni, Petru; Correll, Christoph U; Nielsen, Jimmi; Burtea, Victoria; Kane, John M; Manu, Peter

2014-09-01

Clozapine is effective in treatment-refractory bipolar disorder (BD). Guidelines recommend slow titration to prevent seizures, hypotension and myocarditis, but this stance is not supported by comparative data. To evaluate the safety and effectiveness of rapid clozapine titration in BD. Analysis of a consecutive cohort of treatment-refractory BD patients with mixed/manic episode admitted on alternate days to one of two units of a psychiatric hospital. On one unit, clozapine was started at 25mg followed by 25-50mg as needed every 6h (maximum=100mg/day) on day 1, followed by increases of 25-100mg/day. On the other unit, clozapine was initiated with 25mg in day 1, followed by increases of 25-50mg/day. The primary outcome was the number of days from starting clozapine until readiness for discharge, adjusted in logistic regression for the number of antipsychotics tried during the hospitalization, psychotropic co-treatments and presence of psychotic features. Patients subject to rapid (N=44) and standard (N=23) titration were similar in age, gender, smoking status, body mass index, illness severity at baseline and discharge, and highest clozapine dose. Clozapine was discontinued due to hypotension (N=1) and pneumonia (N=1) during rapid titration, and for excessive sedation (N=1) in each titration group. The number of hospital days from starting clozapine until readiness for discharge was 3.8 days shorter in the rapid titration group (12.7±6.3 vs. 16.5±5.8, p=0.0077). Rapid clozapine titration appeared safe and effective for treatment-refractory BD. The potential for shorter hospital stays justifies prospective trials of this method. Copyright © 2014 Elsevier B.V. All rights reserved.

Outcome and Management of Refractory Respiratory Failure With Timely Extracorporeal Membrane OxygenationSingle-Center Experience With Legionella Pneumonia.

PubMed

Roncon-Albuquerque, Roberto; Vilares-Morgado, Rodrigo; van der Heijden, Gert-Jan; Ferreira-Coimbra, João; Mergulhão, Paulo; Paiva, José Artur

2017-01-01

To analyze the management and outcome of patients with refractory respiratory failure complicating severe Legionella pneumonia rescued with extracorporeal membrane oxygenation (ECMO) in our Center. Observational study of patients with refractory respiratory failure treated with ECMO in Hospital S.João (Porto, Portugal), between November 2009 and September 2016. A total of 112 patients rescued with ECMO, of which 14 had Legionella pneumonia. Patients with Legionella pneumonia were slightly older than patients with acute respiratory failure of other etiologies (51 [48-56] vs 45 [35-54]), but with no significant differences in acute respiratory failure severity between groups: Pao 2 /Fio 2 ratio 67 (60-75) versus 69 (55-85) and Respiratory Extracorporeal Membrane Oxygenation Survival Prediction score 4 (1-5) versus 2 (-1-4), respectively. Legionella pneumonia was associated with earlier ECMO initiation (days of invasive mechanical ventilation [IMV] before ECMO: 2.0 [1.0-4.0] vs 5.0 [2.0-9.5]). After IMV adjustment to "lung rest" settings, this group presented higher respiratory system (RS) static compliance (28.7 [18.8-37.4] vs 16.0 [10.0-20.8] mL/cmH 2 O) but required higher ECMO support (blood flow 5.0 [4.3-5.4] vs 4.2 [3.6-4.8]). Patients with Legionella pneumonia had shorter IMV (16 [14-23] vs 27 [20-42] days) and lower incidence of intensive care unit nosocomial infections (35.7% vs 64.3%), with a trend to higher hospital survival (85.7% vs 62.2%; P = .13). In Legionella pneumonia complicated by refractory respiratory failure, ECMO support allowed patient stabilization under lung protective ventilation and high survival rates. Timely ECMO referral should be considered for Legionella pneumonia failing conventional treatment.

Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes.

PubMed

Kaminskas, Edvardas; Farrell, Ann; Abraham, Sophia; Baird, Amy; Hsieh, Li-Shan; Lee, Shwu-Luan; Leighton, John K; Patel, Hasmukh; Rahman, Atiqur; Sridhara, Rajeshwara; Wang, Yong-Cheng; Pazdur, Richard

2005-05-15

This article summarizes data submitted to the U.S. Food and Drug Administration for marketing approval of azacitidine as injectable suspension (Vidaza, Pharmion Corporation, Boulder, CO) for treatment of patients with myelodysplastic syndrome. In one phase 3 controlled trial, 191 study subjects were randomized to treatment with azacitidine or to observation; an additional 120 patients were treated with azacitidine in two phase 2 single arm studies. The primary efficacy end point was the overall response rate, defined as complete or partial normalization of peripheral blood counts and bone marrow blast percentages for at least 4 weeks. In the controlled trial, the overall response rate was 15.7% in the azacitidine treatment group; there were no responders in the observation group (P < 0.0001). Response rates were similar in the two single arm studies. During response patients stopped being red cell or platelet transfusion dependent. Median duration of responses was at least 9 months. An additional 19% of azacitidine-treated patients had less than partial responses, most becoming transfusion independent. The most common adverse events attributed to azacitidine were gastrointestinal, hematologic, local (injection site), and constitutional. There were no azacitidine-related deaths. On May 19, 2004 the U.S. Food and Drug Administration approved azacitidine as injectable suspension for treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. Full prescribing information is available at http://www.fda.gov/cder/foi/label/2004/050794lbl.pdf. Azacitidine is the first agent approved for treatment of myelodysplastic syndrome.

Predictive factors and outcomes for ibrutinib therapy in relapsed/refractory mantle cell lymphoma-a "real world" study.

PubMed

Epperla, Narendranath; Hamadani, Mehdi; Cashen, Amanda F; Ahn, Kwang W; Oak, Eunhye; Kanate, Abraham S; Calzada, Oscar; Cohen, Jonathon B; Farmer, Luke; Ghosh, Nilanjan; Tallarico, Michael; Nabhan, Chadi; Costa, Luciano J; Kenkre, Vaishalee P; Hari, Parameswaran N; Fenske, Timothy S

2017-12-01

Ibrutinib has demonstrated significant activity in relapsed/refractory mantle cell lymphoma (MCL) in clinical trials. However, the impact of hematopoietic cell transplantation on the outcomes of ibrutinib and the predictive factors for ibrutinib response has not been well studied. Hence, we conducted a multicenter retrospective study of MCL patients who received ibrutinib to (1) determine the overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) of ibrutinib in routine clinical practice, (2) examine characteristics predictive of response to ibrutinib therapy, and (3) describe the outcomes of patients failing ibrutinib. Ninety-seven patients met the eligibility criteria. Overall response rate and median DOR to ibrutinib were 65% and 17 months, respectively. Only lack of primary refractory disease was predictive of ibrutinib response on multivariate analysis. Twenty-nine patients received postibrutinib therapies, with an ORR of 48% and a median DOR of 3 months. The median OS and PFS for the entire group (n = 97) was 22 and 15 months, respectively. On multivariate analysis, ibrutinib response, low MCL international prognostic index, and absence of primary refractory disease were predictors of better PFS, while ibrutinib response and Eastern Cooperative Oncology Group performance status ≤1 were predictors of better OS. The median OS postibrutinib failure was 2.5 months. Our results confirm the high ORR and DOR of ibrutinib in MCL and that prior hematopoietic cell transplantation does not negatively influence ibrutinib outcomes. Survival following ibrutinib failure is poor with no specific subsequent therapy showing superior activity in this setting. As a result, for select (transplant eligible) patients, allogeneic transplant should be strongly considered soon after ibrutinib response is documented to provide durable responses. Copyright © 2017 John Wiley & Sons, Ltd.

Systemic activity of the avermectins against the cat flea (Siphonaptera: Pulicidae).

PubMed

Zakson-Aiken, M; Gregory, L M; Meinke, P T; Shoop, W L

2001-07-01

Ivermectin has potent systemic activity against numerous species of nematodes and arthropods, but there are some important species in these two groups, such as the cat flea, Ctenocephalides felis (Bouché), that appear to be refractory to it. In an effort to determine if the lack of systemic activity against C. felis is specific to ivermectin, or if it is a class-wide phenomenon, 20 avermectin derivatives were tested in an artificial membrane flea feeding system at concentrations of 20, 10, and 1 microg/ml. Results showed that ivermectin had LC90 and LC50 values against fleas of 19.1 and 9.9 microg/ml, respectively. Only four of the other 19 compounds evaluated possessed both LC90 and LC50 values more potent than ivermectin and even then the advantage was modest. Among those four compounds was a two-fold increase in potency relative to ivermectin when the LC90 values were considered (range, 9.2-10.3 microg/ml) and a two- to eight-fold increase when the LC50 values were examined (range, 1.23-5.26 microg/ml). Neither the possession nor the number of oleandrosyl sugars on the macrocyclic backbone were relevant for additional flea activity because among these four compounds were two disaccharides, a monosaccharide and an aglycone. Also, bond disposition between C-22 and 23 did not contribute to increase in activity because these molecules comprise members with either single or double bonds. One of these avermectin analogs was scaled-up and tested subcutaneously in a dog at >100 times the commercial ivermectin dosage and zero efficacy was observed against the flea. We conclude that even the best in vitro avermectin does not have the in vivo potential to become a commercial oral or subcutaneous flea treatment for companion animals.

Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2017-10-24

CD19-Positive Neoplastic Cells Present; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Acute Lymphoblastic Leukemia; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

TNF-alpha antagonists and thalidomide for the management of gastrointestinal Behçet's syndrome refractory to the conventional treatment modalities: a case series and review of the literature.

PubMed

Hatemi, Ibrahim; Hatemi, Gulen; Pamuk, Omer Nuri; Erzin, Yusuf; Celik, Aykut Ferhat

2015-01-01

Gastrointestinal involvement of Behçet's syndrome is usually treated with glucocorticoids, 5-aminosalicylic acid compounds and azathioprine. However, some patients are refractory to these conventional therapy modalities. In this paper we report our experience on 13 patients with gastrointestinal involvement of Behçet's syndrome who were refractory to the conventional therapy and who were treated with TNF-alpha antagonists and/or thalidomide. We reviewed the charts of our Behçet's syndrome patients with gastrointestinal involvement and identified those who were treated with TNF-alpha antagonists and/or thalidomide. Demographic features, previous and concomitant drugs, previous surgery, time to remission and duration of remission were tabulated. We also performed a systematic review of publications on gastrointestinal involvement of Behçet's syndrome patients treated with TNF-alpha antagonists and/or thalidomide. Among our 64 patients with gastrointestinal involvement of Behçet's syndrome, we identified 13 (20%) (7 women, 6 men, mean age 27.4±9.4) who had been treated with TNF-alpha antagonists and/or thalidomide. Their previous medications were glucocorticoids (13/13), azathioprine (13/13), 5-aminosalicylic acid derivatives (3/13) and budesonide (1/13). Clinical and endoscopic remission was obtained in 10 patients. One patient died with sepsis. The systematic literature search revealed 91 cases who had used TNF-alpha antagonists and 15 who had used thalidomide. Among the patients who had received TNF-alpha antagonists, clinical remission was obtained in 47/91 patients (51%), while endoscopic remission was observed in 21/46 (45%) who had a control colonoscopy. One fifth of our Behçet's syndrome patients with gastrointestinal involvement were refractory to conventional treatment modalities. Remission was obtained with TNF-alpha antagonists and/or thalidomide in about 75% of the cases.

Autologous platelet-rich gel for treatment of diabetic chronic refractory cutaneous ulcers: A prospective, randomized clinical trial.

PubMed

Li, Lan; Chen, Dawei; Wang, Chun; Yuan, Nanbing; Wang, Yan; He, Liping; Yang, Yanzhi; Chen, Lihong; Liu, Guanjian; Li, Xiujun; Ran, Xingwu

2015-01-01

The purpose of the study is to examine the safety and effectiveness of topical autologous platelet-rich gel (APG) application on facilitating the healing of diabetic chronic refractory cutaneous ulcers. The study was designed as a prospective, randomized controlled trial between January 1, 2007 and December 31, 2011. Eligible inpatients at the Diabetic Foot Care Center of West China Hospital, Sichuan University (China) were randomly prescribed with a 12-week standard treatment of ulcers (the control group) or standard treatment plus topical application APG (the APG group). The wound healing grades (primary endpoint), time to complete healing, and healing velocity within 12 weeks were monitored as short-term effectiveness measurements, while side effects were documented safety endpoints. The rates of survival and recurrence within the follow up were recorded as long-term effectiveness endpoints. Analysis on total diabetic ulcers (DUs) (n = 117) and subgroup analysis on diabetic foot ulcers (DFUs) (n = 103) were both conducted. Standard treatment plus APG treatment was statistically more effective than standard treatment (p < 0.05 in both total DUs and subgroup of DFUs). The subjects defined as healing grade 1 were 50/59 (84.8%) in total DUs and 41/48 (85.4%) in DFUs in the APG group compared with 40/58 (69.0%) and 37/55 (67.3%) in the control group from intent to treat population. The Kaplan-Meier time-to-healing were significantly different between the two groups (p < 0.05 in both total DUs and subgroup of DFUs). No side effects were identified after topical APG application. The long-term survival and recurrence rates were comparative between groups (p > 0.05). This study shows that topical APG application plus standard treatment is safe and quite effective on diabetic chronic refractory cutaneous ulcers, compared with standard treatment. © 2015 by the Wound Healing Society.

Successful Optimization of Adalimumab Therapy in Refractory Uveitis Due to Behçet's Disease.

PubMed

Martín-Varillas, José Luis; Calvo-Río, Vanesa; Beltrán, Emma; Sánchez-Bursón, Juan; Mesquida, Marina; Adán, Alfredo; Hernandez, María Victoria; Garfella, Marisa Hernández; Pascual, Elia Valls; Martínez-Costa, Lucía; Sellas-Fernández, Agustí; Cordero-Coma, Miguel; Díaz-Llopis, Manuel; Gallego, Roberto; Salom, David; Ortego, Norberto; García-Serrano, José L; Callejas-Rubio, José-Luis; Herreras, José M; García-Aparicio, Ángel; Maíz, Olga; Blanco, Ana; Torre, Ignacio; Díaz-Valle, David; Pato, Esperanza; Aurrecoechea, Elena; Caracuel, Miguel A; Gamero, Fernando; Minguez, Enrique; Carrasco-Cubero, Carmen; Olive, Alejandro; Vázquez, Julio; Ruiz-Moreno, Oscar; Manero, Javier; Muñoz-Fernández, Santiago; Martinez, Myriam Gandía; Rubio-Romero, Esteban; Toyos-Sáenz de Miera, F Javier; López Longo, Francisco Javier; Nolla, Joan M; Revenga, Marcelino; González-Vela, Carmen; Loricera, Javier; Atienza-Mateo, Belén; Demetrio-Pablo, Rosalía; Hernández, José Luis; González-Gay, Miguel A; Blanco, Ricardo

2018-03-27

To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behçet disease (BD) who achieved remission after the use of this biologic agent. Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3-12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean ± standard deviation follow-up of 34.7±13.3 and 26±21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and cost-effective. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Management of refractory status epilepticus in adults

PubMed Central

Rossetti, Andrea O.; Lowenstein, Daniel H.

2011-01-01

Summary Refractory status epilepticus (RSE) can be defined as status epilepticus that continues despite treatment with benzodiazepines and one antiepileptic drug. RSE should be treated promptly to prevent morbidity and mortality; however, scarce evidence is available to support the choice of specific treatments. Major independent outcome predictors are age (not modifiable) and etiology (that should be actively targeted). Recent recommendations for adults, relying upon limited evidence, suggest that RSE treatment aggressiveness should be tailored to the clinical situation: to minimize ICU-related complications, focal RSE without major consciousness impairment might initially be approached more conservatively; conversely, early induction of pharmacological coma is advisable in generalized-convulsive forms. At this stage, midazolam, propofol or barbiturates represent the most used alternatives. Several other treatments, such as additional anesthetics, other antiepileptic or immunomodulatory compounds, or non-pharmacological approaches (electroconvulsive treatment, hypothermia), have been used in protracted RSE. Treatment lasting weeks or months may sometimes result in a good outcome, as in selected cases after cerebral anoxia and encephalitis. Well-designed prospective studies of this condition are urgently needed. PMID:21939901

Phosphorus recovery from fosfomycin pharmaceutical wastewater by wet air oxidation and phosphate crystallization.

PubMed

Qiu, Guanglei; Song, Yonghui; Zeng, Ping; Xiao, Shuhu; Duan, Liang

2011-06-01

Fosfomycin pharmaceutical wastewater contains highly concentrated and refractory antibiotic organic phosphorus (OP) compounds. Wet air oxidation (WAO)-phosphate crystallization process was developed and applied to fosfomycin pharmaceutical wastewater pretreatment and phosphorus recovery. Firstly, WAO was used to transform concentrated and refractory OP substances into inorganic phosphate (IP). At 200°C, 1.0MPa and pH 11.2, 99% total OP (TOP) was transformed into IP and 58% COD was reduced. Subsequently, the WAO effluent was subjected to phosphate crystallization process for phosphorus recovery. At Ca/P molar ratio 2.0:1.0 or Mg/N/P molar ratio 1.1:1.0:1.0, 99.9% phosphate removal and recovery were obtained and the recovered products were proven to be hydroxyapatite and struvite, respectively. After WAO-phosphate crystallization, the BOD/COD ratio of the wastewater increased from 0 to more than 0.5, which was suitable for biological treatment. The WAO-phosphate crystallization process was proven to be an effective method for phosphorus recovery and for fosfomycin pharmaceutical wastewater pretreatment. Copyright © 2011 Elsevier Ltd. All rights reserved.

An XPS study of the adherence of refractory carbide, silicide, and boride RF-sputtered wear-resistant coatings. [X-ray Photoelectron Spectroscopy of steel surfaces

NASA Technical Reports Server (NTRS)

Brainard, W. A.; Wheeler, D. R.

1978-01-01

Radio frequency sputtering was used to deposit refractory carbide, silicide, and boride coatings on 440-C steel substrates. Both sputter etched and pre-oxidized substrates were used and the films were deposited with and without a substrate bias. The composition of the coatings was determined as a function of depth by X-ray photoelectron spectroscopy combined with argon ion etching. Friction and wear tests were conducted to evaluate coating adherence. In the interfacial region there was evidence that bias may produce a graded interface for some compounds. Biasing, while generally improving bulk film stoichiometry, can adversely affect adherence by removing interfacial oxide layers. Oxides of all film constituents except carbon and iron were present in all cases but the iron oxide coverage was only complete on the preoxidized substrates. The film and iron oxides were mixed in the MoSi2 and Mo2C films but layered in the Mo2B5 films. In the case of mixed oxides, preoxidation enhanced film adherence. In the layered case it did not.

Compounds Derived from the Bhutanese Daisy, Ajania nubigena, Demonstrate Dual Anthelmintic Activity against Schistosoma mansoni and Trichuris muris

PubMed Central

Pearson, Mark S.; Giacomin, Paul R.; Becker, Luke; Sotillo, Javier; Pickering, Darren

2016-01-01

Background Whipworms and blood flukes combined infect almost one billion people in developing countries. Only a handful of anthelmintic drugs are currently available to treat these infections effectively; there is therefore an urgent need for new generations of anthelmintic compounds. Medicinal plants have presented as a viable source of new parasiticides. Ajania nubigena, the Bhutanese daisy, has been used in Bhutanese traditional medicine for treating various diseases and our previous studies revealed that small molecules from this plant have antimalarial properties. Encouraged by these findings, we screened four major compounds isolated from A. nubigena for their anthelmintic properties. Methodology/Principal Findings Here we studied four major compounds derived from A. nubigena for their anthelmintic properties against the nematode whipworm Trichuris muris and the platyhelminth blood fluke Schistosoma mansoni using the xWORM assay technique. Of four compounds tested, two compounds—luteolin (3) and (3R,6R)-linalool oxide acetate (1)—showed dual anthelmintic activity against S. mansoni (IC50 range = 5.8–36.9 μg/mL) and T. muris (IC50 range = 9.7–20.4 μg/mL). Using scanning electron microscopy, we determined luteolin as the most efficacious compound against both parasites and additionally was found effective against the schistosomula, the infective stage of S. mansoni (IC50 = 13.3 μg/mL). Luteolin induced tegumental damage to S. mansoni and affected the cuticle, bacillary bands and bacillary glands of T. muris. Our in vivo assessment of luteolin (3) against T. muris infection at a single oral dosing of 100 mg/kg, despite being significantly (27.6%) better than the untreated control group, was markedly weaker than mebendazole (93.1%) in reducing the worm burden in mice. Conclusions/Significance Among the four compounds tested, luteolin demonstrated the best broad-spectrum activity against two different helminths—T. muris and S. mansoni—and was effective against juvenile schistosomes, the stage that is refractory to the current gold standard drug, praziquantel. Medicinal chemistry optimisation including cytotoxicity analysis, analogue development and structure-activity relationship studies are warranted and could lead to the identification of more potent chemical entities for the control of parasitic helminths of humans and animals. PMID:27490394

Interferon Alpha-2a Therapy in Patients with Refractory Behçet Uveitis.

PubMed

Hasanreisoglu, Murat; Cubuk, Mehmet Ozgur; Ozdek, Sengul; Gurelik, Gokhan; Aktas, Zeynep; Hasanreisoglu, Berati

2017-02-01

To report the results of IFNα2a therapy in patients with Behçet uveitis refractory to azathioprine-cyclosporine combination treatment. In a retrospective study, 39 patients treated with either azathioprine-cyclosporine combination treatment (group 1, n = 23) or IFNα2a (group 2, n = 16) with a diagnosis of ocular Behçet disease (BD), were included in the study. Group 2 consisted of patients who did not respond to conventional combination therapy, and were therefore treated with IFNα2a. Clinical response and relapse rates were recorded for each group. The mean number of uveitis attacks/year per patient was 0.8 ± 1.6 in Group 1. In Group 2, a significant decrease in the mean number of uveitis attacks/year per patient was observed after initiation of IFNα2a (2.4 ± 1.8 vs 1.3 ± 2.0) (p<0.05). When the two groups were compared after administration of IFNα2a therapy, no statistical difference was found in terms of uveitis attack/year and attack-free intervals, with a partial response to both treatments. IFNα2a therapy is an effective alternative for Behçet uveitis patients where conventional combination therapy fails.

Platelet-rich plasma as an adjuvant in the endometrial preparation of patients with refractory endometrium.

PubMed

Molina, Aixa; Sánchez, Jose; Sánchez, William; Vielma, Vanessa

2018-03-01

To improve endometrial quality and implantation rates after the administration of platelet-rich plasma in patients with refractory endometrium. 19 patients undergoing in vitro fertilization, aged between 33 and 45 years with a history of refractory endometrium, to whom platelet rich plasma was given by infusion with a catheter into the uterine cavity on the tenth day of the hormone replacement therapy, and then 72 hours after the first administration. Endometrial thicknesses >7mm was reported with the first use; and in all cases, endometrial thicknesses >9mm were evident after the second administration. The entire study group qualified for Embryo Transfer at the blastocyst stage. We had 73.7% of positive pregnancy tests, of which 26.3% yielded live births; 26.3% ongoing pregnancies; 10.5% biochemical pregnancies; 5.3% anembryonic pregnancies and 5.3% had fetal death (16 weeks). Platelet-rich plasma and its biostimulation effects on the endometrial microvasculature seems to be beneficial to patients with refractory endometrium, providing an increase in endometrial receptivity and a consequent increase in implantation rates. As an autologous resource, they are easy to obtain and inexpensive. Thus, we recommend it to be included in the different protocols for endometrial preparation, including those in which a natural cycle is preferred.

Platelet-rich plasma as an adjuvant in the endometrial preparation of patients with refractory endometrium

PubMed Central

Molina, Aixa; Sánchez, Jose; Sánchez, William; Vielma, Vanessa

2018-01-01

Objective To improve endometrial quality and implantation rates after the administration of platelet-rich plasma in patients with refractory endometrium. Methods 19 patients undergoing in vitro fertilization, aged between 33 and 45 years with a history of refractory endometrium, to whom platelet rich plasma was given by infusion with a catheter into the uterine cavity on the tenth day of the hormone replacement therapy, and then 72 hours after the first administration. Results Endometrial thicknesses >7mm was reported with the first use; and in all cases, endometrial thicknesses >9mm were evident after the second administration. The entire study group qualified for Embryo Transfer at the blastocyst stage. We had 73.7% of positive pregnancy tests, of which 26.3% yielded live births; 26.3% ongoing pregnancies; 10.5% biochemical pregnancies; 5.3% anembryonic pregnancies and 5.3% had fetal death (16 weeks). Conclusions Platelet-rich plasma and its biostimulation effects on the endometrial microvasculature seems to be beneficial to patients with refractory endometrium, providing an increase in endometrial receptivity and a consequent increase in implantation rates. As an autologous resource, they are easy to obtain and inexpensive. Thus, we recommend it to be included in the different protocols for endometrial preparation, including those in which a natural cycle is preferred. PMID:29303234

Classical Hodgkin's lymphoma: the Lymphoma Study Association guidelines for relapsed and refractory adult patients eligible for transplant.

PubMed

Van Den Neste, Eric; Casasnovas, Olivier; André, Marc; Touati, Mohamed; Senecal, Delphine; Edeline, Véronique; Stamatoullas, Aspasia; Fornecker, Luc; Deau, Bénédicte; Gastinne, Thomas; Reman, Oumédaly; Gaillard, Isabelle; Borel, Cécile; Brice, Pauline; Fermé, Christophe

2013-08-01

The Hodgkin's Lymphoma Committee of the Lymphoma Study Association (LYSA) gathered in 2012 to prepare guidelines on the management of transplant-eligible patients with relapsing or refractory Hodgkin's lymphoma. The working group is made up of a multidisciplinary panel of experts with a significant background in Hodgkin's lymphoma. Each member of the panel of experts provided an interpretation of the evidence and a systematic approach to obtain consensus was used. Grades of recommendation were not required since levels of evidence are mainly based on phase II trials or standard practice. Data arising from randomized trials are emphasized. The final version was endorsed by the scientific council of the LYSA. The expert panel recommends a risk-adapted strategy (conventional treatment, or single/double transplantation and/or radiotherapy) based on three risk factors at progression (primary refractory disease, remission duration < 1 year, stage III/IV), and an early evaluation of salvage chemosensitivity, including (18)fluorodeoxy glucose-positron emission tomography interpreted according to the Deauville scoring system. Most relapsed or refractory Hodgkin's lymphoma patients chemosensitive to salvage should receive high-dose therapy and autologous stem-cell transplantation as standard. Efforts should be made to increase the proportion of chemosensitive patients by alternating non-cross-resistant chemotherapy lines or exploring the role of novel drugs.

Better evidence for earlier assessment and surgical intervention for refractory epilepsy (The BEST study): a mixed methods study protocol.

PubMed

Rapport, Frances; Shih, Patti; Mitchell, Rebecca; Nikpour, Armin; Bleasel, Andrew; Herkes, Geoffrey; Vagholkar, Sanjyot; Mumford, Virginia

2017-08-21

One-third of patients with refractory epilepsy may be candidates for resective surgery, which can lead to positive clinical outcomes if efficiently managed. In Australia, there is currently between a 6-month and 2-year delay for patients who are candidates for respective epilepsy surgery from the point of referral for surgical assessment to the eventual surgical intervention. This is a major challenge for implementation of effective treatment for individuals who could potentially benefit from surgery. This study examines implications of delays following the point of eligibility for surgery, in the assessment and treatment of patients, and the factors causing treatment delays. Mixed methods design: Observations of qualitative consultations, patient and healthcare professional interviews, and health-related quality of life assessments for a group of 10 patients and six healthcare professionals (group 1); quantitative retrospective medical records' reviews examining longitudinal outcomes for 50 patients assessed for, or undergoing, resective surgery between 2014 and 2016 (group 2); retrospective epidemiological study of all individuals hospitalised with a diagnosis of epilepsy in New South Wales (NSW) in the last 5 years (2012-2016; approximately 11 000 hospitalisations per year, total 55 000), examining health services' use and treatment for individuals with epilepsy, including refractory surgery outcomes (group 3). Ethical approval has been granted by the North Sydney Local Health District Human Research Ethics Committee (HREC/17/HAWKE/22) and the NSW Population & Health Services Research Ethics Committee (HREC/16/CIPHS/1). Results will be disseminated through publications, reports and conference presentations to patients and families, health professionals and researchers. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effects of gut-directed hypnotherapy on IBS in different clinical settings-results from two randomized, controlled trials.

PubMed

Lindfors, Perjohan; Unge, Peter; Arvidsson, Patrik; Nyhlin, Henry; Björnsson, Einar; Abrahamsson, Hasse; Simrén, Magnus

2012-02-01

Gut-directed hypnotherapy has been found to be effective in irritable bowel syndrome (IBS). However, randomized, controlled studies are rare and few have been performed outside highly specialized research centers. The objective of this study was to study the effect of gut-directed hypnotherapy in IBS in different clinical settings outside the traditional research units. The study population included IBS patients refractory to standard management. In study 1, patients were randomized to receive gut-directed hypnotherapy (12 sessions, 1 h/week) in psychology private practices or supportive therapy, whereas patients were randomized to receive gut-directed hypnotherapy in a small county hospital or to serve as waiting list controls in study 2. Gastrointestinal symptom severity and quality of life were evaluated at baseline, at 3 months follow-up and after 1 year. We randomized 138 IBS patients refractory to standard management, 90 in study 1 and 48 in study 2. In both the studies, IBS-related symptoms were improved at 3 months in the gut-directed hypnotherapy groups (P<0.05), but not in the control groups (ns). In study 1, a significantly greater improvement of IBS-related symptom severity could be detected in the gut-directed hypnotherapy group than in the control group (P<0.05), and a trend in the same direction was seen in study 2 (P=0.17). The results seen at 3 months were sustained up to 1 year. Gut-directed hypnotherapy is an effective treatment alternative for patients with refractory IBS, but the effectiveness is lower when the therapy is given outside the highly specialized research centers.

Survival outcomes of patients with germ cell tumors treated with high-dose chemotherapy for refractory or relapsing disease.

PubMed

Zschäbitz, Stefanie; Distler, Florian A; Krieger, Benjamin; Wuchter, Patrick; Schäfer-Eckart, Kerstin; Jenzer, Maximilian; Hohenfellner, Markus; Dreger, Peter; Haag, Georg Martin; Jäger, Dirk; Pahernik, Sascha; Grüllich, Carsten

2018-04-27

Male patients with metastatic germ cell tumors can be cured in up to 96% of cases depending on stage and IGCCCG prognosis group. Treatment in relapse consists of conventional or high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) combined with local treatment modalities. Most patients were classified as poor risk according to IGCCCG ( n = 24; 52%) and as intermediate ( n = 12), high ( n = 16), or very high risk ( n = 9) at time of first relapse according to IPFSG criteria. In 67% of patients ( n = 31) HDCT/ASCT was performed as first salvage treatment in relapse or for primary refractory disease following first line chemotherapy. In 46% of patients ( n = 21) progressive disease was documented after mobilization and prior to HDCT/ASCT. Median progression free survival (mPFS) was 7.4 months (95% confidence interval (CI): 1.3-13.6) while median overall survival (mOS) was 22.2 months (95% CI: 8.9-35.5). When stratified for IPFSG risk group, mPFS ( p < 0.001) and mOS ( p = 0.009) differed significantly between risk groups (very low vs. low vs. intermediate vs. high vs. very high). Metastases to liver/bone/brain and platinum refractory disease were independent risk factors for inferior PFS ( p = 0.024; p = 0.008) but not OS. Forty-six patients treated with HDCT/ASCT at the university clinics in Heidelberg and Nuremberg between 2000-2016 were identified and analyzed. Data was collected retrospectively. HDCT/ASCT offers a potential curative strategy for patients with relapsed GCT. Improvement is still needed in patients with intermediate, high, and very high IPFSG risk group.

A review on the effects of current chemotherapy drugs and natural agents in treating non–small cell lung cancer

PubMed Central

Huang, Chih-Yang; Ju, Da-Tong; Chang, Chih-Fen; Muralidhar Reddy, P.; Velmurugan, Bharath Kumar

2017-01-01

Lung cancer is the leading cause of cancer deaths worldwide, and this makes it an attractive disease to review and possibly improve therapeutic treatment options. Surgery, radiation, chemotherapy, targeted treatments, and immunotherapy separate or in combination are commonly used to treat lung cancer. However, these treatment types may cause different side effects, and chemotherapy-based regimens appear to have reached a therapeutic plateau. Hence, effective, better-tolerated treatments are needed to address and hopefully overcome this conundrum. Recent advances have enabled biologists to better investigate the potential use of natural compounds for the treatment or control of various cancerous diseases. For the past 30 years, natural compounds have been the pillar of chemotherapy. However, only a few compounds have been tested in cancerous patients and only partial evidence is available regarding their clinical effectiveness. Herein, we review the research on using current chemotherapy drugs and natural compounds (Wortmannin and Roscovitine, Cordyceps militaris, Resveratrol, OSU03013, Myricetin, Berberine, Antroquinonol) and the beneficial effects they have on various types of cancers including non-small cell lung cancer. Based on this literature review, we propose the use of these compounds along with chemotherapy drugs in patients with advanced and/or refractory solid tumours. PMID:29130448

Current Diagnosis and Management of Suspected Reflux Symptoms Refractory to Proton Pump Inhibitor Therapy

PubMed Central

2014-01-01

Suspected reflux symptoms that are refractory to proton pump inhibitors (PPIs) are rapidly becoming the most common presentation of gastroesophageal reflux disease (GERD) in patients seen in gastroenterology clinics. These patients are a heterogeneous group, differing in symptom frequency and severity, PPI dosing regimens, and responses to therapy (from partial to absent). Before testing, the physician needs to question the patient carefully about PPI compliance and the timing of drug intake in relation to meals. Switching PPIs or doubling the dose is the next step, but only 20% to 25% of the group refractory to PPIs will respond. The first diagnostic test should be upper gastrointestinal endoscopy. In more than 90% of cases, the results will be normal, but persistent esophagitis may suggest pill esophagitis, eosinophilic esophagitis, or rarer diseases, such as lichen planus, Zollinger-Ellison syndrome, or genotype variants of PPI metabolism. If the endoscopy results are normal, esophageal manometry and especially reflux testing should follow. Whether patients should be tested on or off PPI therapy is controversial. Most physicians prefer to test patients off PPIs to identify whether abnormal acid reflux is even present; if it is not, PPIs can be stopped and other diagnoses sought. Testing patients on PPI therapy allows nonacid reflux to be identified, but more than 50% of patients have a normal test result, leaving the clinician with a conundrum—whether to stop PPIs or continue them because the GERD is being treated adequately. Alternative diagnoses in patients with refractory GERD and normal reflux testing include achalasia, eosinophilic esophagitis, gastroparesis, rumination, and aerophagia. However, more than 50% will be given the diagnosis of functional heartburn, a visceral hypersensitivity syndrome. Treating patients with PPI-refractory GERD–like symptoms can be difficult and frustrating. Any of the following may help: a histamine-2 receptor antagonist at night, baclofen to decrease transient lower esophageal sphincter relaxations, pain modulators, acupuncture, or hypnotherapy. At this time, antireflux surgery should be limited to patients with abnormal acid reflux defined by pH testing and a good correlation of symptoms with acid reflux. PMID:27551249

Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-20

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Hodgkin Lymphoma; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; EZH2 Gain of Function; EZH2 Gene Mutation; Histiocytosis; Loss of BRG1 Protein Expression; Loss of INI 1 Protein Expression; Low Grade Glioma; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Hodgkin Lymphoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Central Nervous System Neoplasm; Refractory Hodgkin Lymphoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Soft Tissue Sarcoma; Rhabdoid Tumor; SMARCA4 Gene Inactivation; SMARCB1 Gene Inactivation; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Wilms Tumor

Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group.

PubMed

Buckstein, Rena; Kuruvilla, John; Chua, Neil; Lee, Christina; Macdonald, David A; Al-Tourah, Abdulwahab J; Foo, Alison H; Walsh, Wendy; Ivy, S Percy; Crump, Michael; Eisenhauer, Elizabeth A

2011-05-01

There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3-4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity.

Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group

PubMed Central

Buckstein, Rena; Kuruvilla, John; Chua, Neil; Lee, Christina; Macdonald, David A; Al-Tourah, Abdulwahab J; Foo, Alison H; Walsh, Wendy; Ivy, S Percy; Crump, Michael; Eisenhauer, Elizabeth A

2011-01-01

There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3—4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity. PMID:21463120

Anthropometric Indices in Children With Refractory Epilepsy.

PubMed

Aminzadeh, Vahid; Dalili, Setila; Ashoorian, Yalda; Kohmanaee, Shahin; Hassanzadeh Rad, Afagh

2016-01-01

We aimed to assess the effect of body mass index (BMI) on reducing the risk of refractory seizure due to lipoid tissue factors. This matched case-control study, consisted of cases (Patients with refractory epilepsy) and controls (Healthy children) referred to 17 Shahrivar Hospital, Guilan University of Medical Sciences, Guilan, Iran during 2013-2014. Data were gathered by a form including demographic characteristics, type of epilepsy, predominant time of epilepsy, therapeutic approach, frequency of epilepsy, time of disease onset and anthropometric indices. We measured anthropometric indices and transformed them into Z-scores. Data were reported by descriptive statistics (mean and standard deviation) and analyzed by Pearson correlation coefficient, paired t test and multinomial regression analysis test using SPSS 19. There was no significant difference between sex groups regarding anthropometric indices. Generalized and focal types of epilepsies were noted on 57.5% and 38.75% of patients, respectively. Daytime epilepsies happened in 46.25% of patients and 33.75% noted no predominant time for epilepsies. Clinicians indicated poly-therapy for the majority of patients (92.5%). The most common onset times for epilepsies were 36-72 months for 32.5% of patients. Lower onset time indicated lower frequency of refractory epilepsies. Although, there was significant difference between Zheight and predominant time of epilepsies but no significant relation was found between types of epilepsies and frequency of epilepsies with anthropometric indices. Using multivariate regression analysis by backward LR, Zweight and birth weight were noted as the predicting factors of refractory epilepsies. This effect may be because of leptin. Therefore, researchers recommend further investigations regarding this issue in children with epilepsy.

The health-related quality of life of children with refractory epilepsy: a comparison of those with and without intellectual disability.

PubMed

Sabaz, M; Cairns, D R; Lawson, J A; Bleasel, A F; Bye, A M

2001-05-01

To determine whether refractory epilepsy affects the health-related quality of life (HRQOL) of children with or without intellectual disability (ID), and if the presence of ID independently compromises HRQOL in children with refractory epilepsy. Subjects were parents of children with refractory epilepsy, whose syndrome had been defined using ILAE (International League Against Epilepsy) criteria and video-EEG monitoring. Children had the presence or absence of ID determined by formal neuropsychological or educational assessment. The relative effect of epilepsy on the two intellectual ability groups was determined using relevant clinical variables. Parents completed a valid epilepsy-specific HRQOL questionnaire for children, the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE), and, depending on intellectual ability level, the Child Behaviour Checklist or Developmental Behaviour Checklist. Both intellectually normal children with epilepsy and children with epilepsy and ID were more likely to have psychosocial problems compared with their respective intellectual ability reference populations. The results also revealed that children with ID had reduced HRQOL compared with intellectually normal children; a result independent of epilepsy. Analysis of the relationship between epilepsy variables and HRQOL revealed that the QOLCE was the most sensitive in detecting variation in age at onset, seizure frequency, and medications taken. The HRQOL of children with refractory epilepsy is greatly affected, regardless of intellectual ability level. The presence of ID in children with epilepsy independently depresses HRQOL outcomes. Compared with two generic HRQOL measures, the QOLCE was the most sensitive measure to variation in epilepsy variables.

Electrochemical oxidation of nitrogen-heterocyclic compounds at boron-doped diamond electrode.

PubMed

Xing, Xuan; Zhu, Xiuping; Li, Hongna; Jiang, Yi; Ni, Jinren

2012-01-01

Nitrogen-heterocyclic compounds (NHCs) are toxic and bio-refractory contaminants widely spread in environment. This study investigated electrochemical degradation of NHCs at boron-doped diamond (BDD) anode with particular attention to the effect of different number and position of nitrogen atoms in molecular structure. Five classical NHCs with similar structures including indole (ID), quinoline (QL), isoquinoline (IQL), benzotriazole (BT) and benzimidazole (BM) were selected as the target compounds. Results of bulk electrolysis showed that degradation of all NHCs was fit to a pseudo first-order equation. The five compounds were degraded with the following sequence: ID>QL>IQL>BT>BM in terms of their rates of oxidation. Quantum chemical calculation was combined with experimental results to describe the degradation character of NHCs at BDD anode. A linear relationship between degradation rate and delocalization energy was observed, which demonstrated that electronic charge was redistributed through the conjugation system and accumulated at the active sites under the attack of hydroxyl radicals produced at BDD anode. Moreover, atom charge was calculated by semi empirical PM3 method and active sites of NHCs were identified respectively. Analysis of intermediates by GC-MS showed agreement with calculation results. Copyright © 2011 Elsevier Ltd. All rights reserved.

Copper diffusion in Ti Si N layers formed by inductively coupled plasma implantation

NASA Astrophysics Data System (ADS)

Ee, Y. C.; Chen, Z.; Law, S. B.; Xu, S.; Yakovlev, N. L.; Lai, M. Y.

2006-11-01

Ternary Ti-Si-N refractory barrier films of 15 nm thick was prepared by low frequency, high density, inductively coupled plasma implantation of N into TixSiy substrate. This leads to the formation of Ti-N and Si-N compounds in the ternary film. Diffusion of copper in the barrier layer after annealing treatment at various temperatures was investigated using time-of-flight secondary ion mass spectrometer (ToF-SIMS) depth profiling, X-ray diffractometer (XRD), field emission scanning electron microscopy (FESEM), energy dispersive X-ray (EDX) and sheet resistance measurement. The current study found that barrier failure did not occur until 650 °C annealing for 30 min. The failure occurs by the diffusion of copper into the Ti-Si-N film to form Cu-Ti and Cu-N compounds. FESEM surface morphology and EDX show that copper compounds were formed on the ridge areas of the Ti-Si-N film. The sheet resistance verifies the diffusion of Cu into the Ti-Si-N film; there is a sudden drop in the resistance with Cu compound formation. This finding provides a simple and effective method of monitoring Cu diffusion in TiN-based diffusion barriers.

Ibrutinib in Treating Patients With Refractory or Relapsed Lymphoma After Donor Stem Cell Transplant

ClinicalTrials.gov

2017-10-03

Blastoid Variant Mantle Cell Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Follicular Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma

Development of refractories and related products for steel melting, finishing, and casting

NASA Astrophysics Data System (ADS)

Smirnov, A. N.

2013-06-01

The transformation of the consumption of refractories for the production, out-of-furnace treatment, and casting of steel is considered. The main trends in developing the refractory market are shown to be a significant decrease in the specific consumption of refractories per 1 t liquid steel and the predominant application of refractories based on magnesia raw materials and fused corundum for the working layers of melting units, ladles, and tundishes. The main trend in decreasing the specific costs of refractories is the development of refractories based on alternative sources of raw materials, which are cheaper and more available for refractory manufacturers.

Pembrolizumab Alone or With Idelalisib or Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Non-Hodgkin Lymphomas

ClinicalTrials.gov

2017-06-30

Recurrent Chronic Lymphocytic Leukemia; Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Nodal Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Splenic Marginal Zone Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Nodal Marginal Zone Lymphoma; Refractory Small Lymphocytic Lymphoma; Refractory Splenic Marginal Zone Lymphoma; Richter Syndrome; Waldenstrom Macroglobulinemia

Brentuximab vedotin for relapsed or refractory CD30+ hematologic malignancies: the German Hodgkin Study Group experience.

PubMed

Rothe, Achim; Sasse, Stephanie; Goergen, Helen; Eichenauer, Dennis A; Lohri, Andreas; Jäger, Ulrich; Bangard, Christopher; Böll, Boris; von Bergwelt Baildon, Michael; Theurich, Sebastian; Borchmann, Peter; Engert, Andreas

2012-08-16

The CD30-targeting Ab-drug conjugate brentuximab vedotin (SGN-35) was recently approved for the treatment of relapsed Hodgkin lymphoma and anaplastic large-cell lymphoma by the Food and Drug Administration. In the present study, we report the experience of the German Hodgkin Study Group with brentuximab vedotin as single agent in 45 patients with refractory or relapsed CD30(+) Hodgkin lymphoma who were treated either in a named patient program (n = 34) or in the context of a safety study associated with the registration program of this drug. In these very heavily pretreated patients, an objective response rate of 60%, including 22% complete remissions, could be documented. The median duration of response was 8 months. This retrospective analysis supports the previously reported excellent therapeutic efficacy of brentuximab vedotin in heavily pretreated CD30(+) malignancies.

Late glaucoma after interstitial keratitis.

PubMed

Grant, W M

1975-01-01

In a systematic study of 45 patients who had syphilitic interstitial keratitis early in life and, many years later, were discovered to have glaucoma, there was evidence of two different but equally common mechanisms. In one group of patients, a deep-chamber type of glaucoma was superimposed on old inflammatory changes, was characteristically refractory to medical treatment, but did well with filtering surgery. The other group of patients had reversible angle-closure glaucoma associated with anatomically small anterior segments, and typically responded well to iridectomy. The late, refractory, deep-chamber type of glaucoma may involve endothelialization and formation of glass membrane in the angle, as seen in one excised eye. Occurrence of the shallow-chamber, reversible angle-closure type of glaucoma after interstitial keratitis may be coincidental, since no other evidence supports the idea that small anterior segments might be particularly prevalent among patients who have had congenital syphilis or interstitial keratitis.

Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination With Fludarabine and Cytarabine, in Pediatric Relapsed or Refractory Acute Leukemia.

PubMed

Alexander, Thomas B; Lacayo, Norman J; Choi, John K; Ribeiro, Raul C; Pui, Ching-Hon; Rubnitz, Jeffrey E

2016-12-01

Purpose To characterize the toxicity, pharmacokinetics, and pharmacodynamics of selinexor, a selective inhibitor of nuclear export, when combined with fludarabine and cytarabine, in children with relapsed or refractory leukemia. Patients and Methods Eighteen patients with relapsed or refractory acute leukemia were enrolled in the SELHEM (Selinexor With Fludarabine and Cytarabine for Treatment of Refractory or Relapsed Leukemia or Myelodysplastic Syndrome) clinical trial (NCT02212561). Selinexor, initially at 30 mg/m 2 per dose, was given orally on days 1, 3, 8, 10, 22, and 24 and was escalated according to a rolling-six design. Fludarabine 30 mg/m 2 and cytarabine 2 g/m 2 were administered on days 15 to 19. Pharmacokinetic and pharmacodynamic studies were performed on days 1 and 22. Response evaluations were performed on day 15 and at the completion of course 1. Results Among the 17 patients who were evaluable for toxicity, three were treated at 30 mg/m 2 , three at 40 mg/m 2 , six at 55 mg/m 2 , and five at 70 mg/m 2 . The most common grade 3 nonhematologic toxicity was asymptomatic hyponatremia. Two patients who were treated at 70 mg/m 2 experienced reversible cerebellar toxicity, thereby defining the dose-limiting toxicity. Pharmacokinetic parameters demonstrated that plasma exposure was dose proportional. Fifteen of 16 patients demonstrated at least a twofold increase of XPO1 mRNA, indicating inhibition of the XPO1 protein. In this group of heavily pretreated, relapsed, and refractory patients, seven of 15 evaluable patients (47%) achieved complete response or complete response with incomplete count recovery. Conclusion Selinexor, in combination with fludarabine and cytarabine, is tolerable at doses up to 55 mg/m 2 in pediatric patients with relapsed or refractory leukemia. All patients who received selinexor at ≥ 40 mg/m 2 demonstrated XPO1 target inhibition. Response rates are promising and will be further explored in a phase II trial.

Chloride channel blockade relaxes airway smooth muscle and potentiates relaxation by β-agonists

PubMed Central

Yim, Peter; Rinderspacher, Alison; Fu, Xiao Wen; Zhang, Yi; Landry, Donald W.; Emala, Charles W.

2014-01-01

Severe bronchospasm refractory to β-agonists continues to cause significant morbidity and mortality in asthmatic patients. We questioned whether chloride channels/transporters are novel targets for the relaxation of airway smooth muscle (ASM). We have screened a library of compounds, derivatives of anthranilic and indanyloxyacetic acid, that were originally developed to antagonize chloride channels in the kidney. We hypothesized that members of this library would be novel calcium-activated chloride channel blockers for the airway. The initial screen of this compound library identified 4 of 20 compounds that relaxed a tetraethylammonium chloride-induced contraction in guinea pig tracheal rings. The two most effective compounds, compounds 1 and 13, were further studied for their potential to either prevent the initiation of or relax the maintenance phase of an acetylcholine (ACh)-induced contraction or to potentiate β-agonist-mediated relaxation. Both relaxed an established ACh-induced contraction in human and guinea pig ex vivo ASM. In contrast, the prevention of an ACh-induced contraction required copretreatment with the sodium-potassium-chloride cotransporter blocker bumetanide. The combination of compound 13 and bumetanide also potentiated relaxation by the β-agonist isoproterenol in guinea pig tracheal rings. Compounds 1 and 13 hyperpolarized the plasma cell membrane of human ASM cells and blocked spontaneous transient inward currents, a measure of chloride currents in these cells. These functional and electrophysiological data suggest that modulating ASM chloride flux is a novel therapeutic target in asthma and other bronchoconstrictive diseases. PMID:24879056

A role for very low-dose recombinant activated factor VII in refractory bleeding after cardiac surgery: Lessons from an observational study.

PubMed

Hoffmann, Till; Assmann, Alexander; Dierksen, Angelika; Roussel, Elisabeth; Ullrich, Sebastian; Lichtenberg, Artur; Albert, Alexander; Sixt, Stephan

2018-04-18

Although off-label use of recombinant activated factor VII against refractory bleeding is incorporated in current guideline recommendations, safety concerns persist predominantly with respect to thromboembolic complications. We analyzed the safety and efficacy of recombinant activated factor VII at a very low dose in cardiosurgical patients with refractory bleeding. This prospective study includes 1180 cardiosurgical patients at risk of bleeding. Goal-directed substitution was based on real-time laboratory testing and clinical scoring of the bleeding intensity. All patients who fulfilled the criteria for enhanced risk of bleeding (n = 281) were consequently included in the present analysis. Patients in whom refractory bleeding developed despite substitution with specific hemostatic compounds (n = 167) received a single shot of very low-dose recombinant activated factor VII (≤20 μg/kg). Mortality and risk of thromboembolic complications, and freedom from stroke and acute myocardial infarction in particular, were analyzed (vs patients without recombinant activated factor VII) by multivariable logistic and Cox regression analyses, as well as Kaplan-Meier estimates. There was no increase in rates of mortality (30-day mortality 4.2% vs 7.0% with P = .418; follow-up survival 85.6% at 13.0 [interquartile range, 8.4-15.7] months vs 80.7% at 10.2 [interquartile range, 7.2-16.1] months with P = .151), thromboembolic complications (6.6% vs 9.6% with P = .637), renal insufficiency, need for percutaneous coronary intervention, duration of ventilation, duration of hospital stay, or rehospitalization in patients receiving very low-dose recombinant activated factor VII compared with patients not receiving recombinant activated factor VII. Complete hemostasis without any need for further hemostatic treatment was achieved after very low-dose recombinant activated factor VII administration in the majority of patients (up to 88.6% vs 0% with P < .001). The key results were confirmed after adjustment by propensity score-based analyses. When combined with early and specific restoration of hemostatic reserves after cardiac surgery, very low-dose recombinant activated factor VII treatment of refractory bleeding is effective and not associated with any apparent increase in adverse events. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Geochemistry of Early Paleozoic boninites from the Central Qilian block, Northwest China: Constraints on petrogenesis and back-arc basin development

NASA Astrophysics Data System (ADS)

Gao, Zhong; Zhang, Hong-Fei; Yang, He; Luo, Bi-Ji; Guo, Liang; Xu, Wang-Chun; Pan, Fa-Bin

2018-06-01

Early Paleozoic boninites occur in the Central Qilian orogenic belt, Northwest China. Their petrogenesis provides insights into lithosphere process and tectonic evolution of the Qilian block. In this paper, we carry out a study of geochronological, geochemical and Sr-Nd isotopic compositions for the Early Paleozoic boninites in the Lajishan area of the Central Qilian block. The Lajishan boninites (∼483 Ma) have high Al2O3/TiO2 (36.7-64.7) and CaO/TiO2 (31.1-49.6) ratios, and high MgO (7.86-10.47 wt%), Cr (439-599 ppm) and Ni (104-130 ppm) contents, indicating that the boninites result from a refractory mantle source. They are depleted in high field-strength elements (HFSE) and enriched in large ion lithophile elements (LILE), coupled with slightly high initial 87Sr/86Sr values of 0.7059-0.7074 and low εNd(t) values of -1.05 to +2.66, indicating that the mantle source was metasomatized by subducted slab-derived components. We found that an assemblage of low-Ca group and high-Ca group boninites occurred in the Lajishan belt. The high-Ca group boninites were derived from relatively fertile mantle with slightly higher melting degree, whereas the low-Ca group boninites were generated by partial melting of more refractory mantle wedge peridotites with slightly lower melting degree. The assemblage of low-Ca group and high-Ca group boninites reveals that the low-Ca group boninites were generated by the further melting of the more refractory mantle source after the segregation of the high-Ca group boninitic magmas in response to the back-arc basin opening. In the light of reported boninites worldwide, a diagram of Zr/Y vs. CaO/Al2O3 is used to identify boninites in fore-arc and back-arc regions. We suggest that the Lajishan boninites represent the products of back-arc basin development in response to the northward subduction of the Qaidam-West Qinling ocean slab.

[The impacts of low-dose corticosteroids infusion given in different manners on refractory septic shock patients].

PubMed

Chen, Zhi; Yang, Chunli; He, Huiwei; He, Zhaohui

2015-06-01

To discuss the influence of different ways of low-dose corticosteroids infusion on hemodynamics, changes in blood glucose level and prognosis in patients with refractory septic shock. A prospective single-blind randomized controlled trial was conducted. Refractory septic shock patients admitted to the Department of Critical Care Medicine of Jiangxi Provincial People's Hospital from April 1st, 2013 to October 31st, 2014 were enrolled for the study. The patients were divided into control group and research group by random number table. Besides conventional treatment for septic shock, patients in control group were given 200 mg/d hydrocortisone intravenous infusion lasting for 2 hours, while those of research group were given 8.33 mg/h hydrocortisone per hour with an intravenous pump. Treatment lasted for 5 continuous days for both groups. The changes in heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP) and arterial blood lactic acid in both groups were observed at the time of enroldment and 6 hours, 24 hours, 48 hours, and 5 days after the treatment. With a dynamic blood glucose monitor, mean blood glucose (MBG) level, largest amplitude of glycemic excursions (LAGE), glucose variability (GV), and the ratio of hyperglycaemia time were recorded. The duration of shock, length of intensive care unit (ICU) stay, total length of hospital stay, and 28-day mortality of both groups were recorded. Seventy-nine septic shock patients were assigned to the treatment, with 41 in control group, and 38 in research group. Compared with control group, 6-hour MAP in research group was obviously lowered [mmHg (1 mmHg=0.133 kPa): 66.31±4.38 vs. 68.58±4.86, t=1.062, P=0.033], but there were no significant differences in HR, MAP, CVP, lactic acid clearance and norepinephrine (NE) utilization rates at other time points between two groups. No significant difference in MBG was found between research group and control group (mmol/L: 8.69±2.14 vs. 9.95±3.87, t=1.771, P=0.080), but LAGE, GV, the ratio of hyperglycemia time in research group were significantly lower than those of the control group [LAGE (mmol/L): 17.18±8.97 vs. 22.71±11.80, t=2.331, P=0.022; GV (mmol/L): 2.57±1.05 vs. 3.16±1.37, t=2.136, P=0.036; the ratio of hyperglycemia time: (43.1±11.7)% vs. (49.4±15.3)%, t=2.044, P=0.044]. There was no statistical difference in the following features between research group and control group, such as the duration of shock (days: 3.47±0.98 vs. 3.61±1.07, t=0.605, P=0.547), length of ICU stay (days: 8.74±3.12 vs. 9.97±3.37, t=1.543, P=0.120), total length of hospital stay (days: 18.34±9.27 vs. 19.58±9.83, t=0.576, P=0.566) and 28-day mortality rate (23.68% vs. 26.83%, χ2=0.103, P=0.748). Compared with slow intravenous infusion, a continuous intravenous supplementation of small amount of hydrocortisone to patients with refractory septic shock could stabilize blood glucose levels and maintain metabolic balance efficiently. However, in both groups there was no significant difference in the efficiency in stabilizing hemodynamics, shortening shock duration, reducing ICU or hospital days and decreasing 28-day mortality.

Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma

ClinicalTrials.gov

2018-02-12

Prolymphocytic Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma; T-Cell Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

Nivolumab and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

ClinicalTrials.gov

2018-01-25

Grade 3a Follicular Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Waldenstrom Macroglobulinemia; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma

Lenalidomide and Ibrutinib in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-03-02

Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma

Lenalidomide in Treating Young Patients With Relapsed or Refractory Solid Tumors or Myelodysplastic Syndromes

ClinicalTrials.gov

2014-06-10

Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Myelodysplastic Syndromes; Unspecified Childhood Solid Tumor, Protocol Specific

A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas

ClinicalTrials.gov

2018-04-11

CD20 Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Transformed Indolent Non-Hodgkin Lymphoma

Trace Element Abundances in Refractory Inclusions from Antarctic Micrometeorites

NASA Astrophysics Data System (ADS)

Greshake, A.; Hoppe, P.; Bischoff, A.

1995-09-01

Refractory inclusions are charcteristic components in carbonaceous chondrites. Therefore, refractory inclusions found in micrometeorites can give important hints about the relationship between micrometeorites and carbonaceous chondrites. So far, only a few inclusions were found in micrometeorites [1-4]. In this study we report the first trace element analysis of perovskite and fassaite found in micrometeorites. We studied two Antarctic micrometeorites by ASEM, EMP, and SIMS. The first particle is 120 micrometers in size mainly consisting of a fine-grained matrix of dehydrated former phyllosilikates that enclose a 5 micrometers sized perovskite [5]. The perovskite is surrounded by a 1 micrometers thick rim of ilmenite and contains up to 1.3 wt% FeO as determined by EMP. The trace element abundances were determined by SIMS following the procedure described by [6]. The REE pattern of the perovskite is shown in Fig. 1. The pattern is closely related to the Group II pattern with its typical depletion of the more refractory REEs [7]. It is also very similar to the REE abundances of perovskite from Murchison (CM) [8] and CH-chondrites [9]. This may indicate a relationship between this micrometeorite and components in carbonaceous chondrites. The second micrometeorite is 100 micrometers in size consisting of a fine-grained (20 micrometers across) and a coarse-grained (80 micrometers across) area. Both areas contain fassaite with different chemical compositions. The particle was previously analyzed by Lindstrom and Kloeck [1] without knowing the mineralogy. We carried out SIMS analysis of each area of the micrometeorite separately. The TEE patterns of these two areas are similar and show in general a Group III pattern (20-30x CI) in which the more refractory REEs are not fractionated. The negative Eu anomaly is much more apparent in the coarse-grained area and no Yb anomaly is apparent in one of the areas. This is the first CAI of a micrometeorite showing a Group III REE pattern. References: [1] Lindstrom D. J. and Kloeck W. (1992) Meteoritics, 27, 250. [2] Kurat G. et al. (1994) Meteoritics, 29, 487-488. [3] Kurat G. et al. (1995) LPS XXV, 763-764. [4] Hoppe P. et al. (1995) LPS XXVI, 623-624. [5] Beckerling W. et al. (1992) Meteoritics, 27, 200-201. [6] Zinner E. and Crozaz G. (1986) Int. J. Mass. Spectr. Ion Processes, 69, 17-38. [7] Martin P. and Mason B. (1974) Nature, 249, 333-334. [8] Ireland T. et al. (1988) GCA, 52, 2841-2854. [9] Weber et al. (1995) GCA, 59, 803-823.

Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial.

PubMed

Glass, Bertram; Hasenkamp, Justin; Wulf, Gerald; Dreger, Peter; Pfreundschuh, Michael; Gramatzki, Martin; Silling, Gerda; Wilhelm, Christian; Zeis, Matthias; Görlitz, Anke; Pfeiffer, Sebastian; Hilgers, Reinhard; Truemper, Lorenz; Schmitz, Norbert

2014-06-01

Allogeneic stem-cell transplantation has had limited success for patients with refractory and relapsed aggressive B-cell or T-cell lymphoma. We investigated the effect of adding rituximab to standard prophylaxis for graft-versus-host disease after transplantation and estimated overall survival when using a lymphoma-directed myeloablative conditioning regimen. We did this randomised, open-label, phase 2 study at seven German transplantation centres. We enrolled patients with aggressive B-cell or T-cell lymphoma and primary refractory disease, early relapse (<12 months after first-line treatment), or relapse after autologous transplantation. Conditioning with fludarabine (125 mg/m(2)), busulfan (12 mg/kg oral or 9·6 mg/kg intravenous), and cyclophosphamide (120 mg/kg) was followed by allogeneic stem-cell transplantation. Patients were randomly assigned (1:1) to receive rituximab (375 mg/m(2) on days 21, 28, 35, 42, 175, 182, 189, and 196) or not. Allocation was done with a centralised computer-generated procedure; patients were stratified by histological subtype (B-cell vs T-cell lymphoma) and donor match (HLA-identical vs non-identical). Neither investigators nor patients were masked to allocation. The primary endpoints were the incidence of acute graft-versus-host disease grade 2-4 in each treatment group and overall survival at 1 year in both groups combined. All analyses were done for the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT00785330. Between June 16, 2004, and March 24, 2009, we screened 86 patients and enrolled 84; 42 were randomly assigned to each group. The cumulative incidence of grade 2-4 acute graft-versus-host disease was 46% (95% CI 32-62) in the rituximab group and 42% (95% CI 29-59) in the no rituximab group (hazard ratio [HR] 0·91, 95% CI 0·52-1·60; p=0·74). Overall survival at 1 year for the whole study population was 52% (95% CI 41-62). Grade 4 haematological toxic effects and grade 3 alopecia occurred in all patients. The most common non-haematological grade 5 toxic effects were pneumonia (nine in the no rituximab group vs ten in the rituximab group) and other infections (seven vs four). The lymphoma-directed myeloablative conditioning regimen developed here is promising for patients with refractory and relapsed aggressive B-cell and T-cell lymphomas. However, the addition of rituximab did not affect the incidence of graft-versus-host disease or overall survival. Hoffmann-La Roche, Amgen, Astellas Pharma. Copyright © 2014 Elsevier Ltd. All rights reserved.

Axicabtagene Ciloleucel Expanded Access Study

ClinicalTrials.gov

2018-05-29

Relapsed/Refractory Diffuse Large B Cell Lymphoma; Relapsed/Refractory Primary Mediastinal B Cell Lymphoma; Relapsed/Refractory Transformed Follicular Lymphoma; Relapsed/Refractory High-Grade B-Cell Lymphoma

An observational study on outcome of hemispherotomy in children with refractory epilepsy.

PubMed

Panigrahi, Manas; Krishnan, Shyam Sundar; Vooturi, Sudhindra; Vadapalli, Rammohan; Somayajula, Shanmukhi; Jayalakshmi, Sita

2016-12-01

The current study aimed to evaluate the clinical characteristics and outcome of hemispherotomy in children with refractory hemispherical epilepsy. Retrospective analysis of data in twenty one children aged ≤12 years who underwent hemispherotomy and had at least two years post surgery follow-up was performed. Sixteen children underwent Delalande's vertical para-sagittal hemispherotomy (VPH), while lateral peri-insular functional hemispherotomy was performed in the rest. The average age of onset for epilepsy in the study population was 2.9 ± 2.4 years; the average duration of epilepsy was 4.0 ± 2.9 years. The mean age at surgery of the study population was 6.8 ± 2.8 years. Six (28.5%) children were girls. Gliosis due to presumed childhood infarct was most common etiology, observed in 13 (62.0%) of the children, followed by Rasmussen's encephalitis in six (28.5%). There was no significant difference between the surgery groups for the reported acute post operative seizures (APOS) (20.0% vs. 25.0%; p = 1.000). At last follow up 90.5% patients were seizure free; there was no difference between the groups for seizure freedom (60.0% vs. 87.5%; p = 0.228). When analyzed for outcome between the etiologies, seizure freedom was similar for gliosis due to infarct (76.9%), Rassmussens encephalitis (83.3%) and malformations of cortical development (MCD) (100.0%). Moreover, improved quality of life in epilepsy (QOLIE) scores was observed in 80.0% of the lateral peri-insular functional hemispherotomy group and 87.5% children in VPH group at the last follow-up. Gliosis due to presumed childhood infarct was the leading cause of medically refractory epilepsy caused by hemispheric lesions in the current study. Encouragingly, hemispherotomy offers seizure freedom (in 90.5% patients) and improvement in QOLIE scores at two years follow up. Copyright © 2015 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Survival analysis of platinum-refractory patients with advanced esophageal cancer treated with docetaxel or best supportive care alone: a retrospective study.

PubMed

Moriwaki, T; Kajiwara, T; Matsumoto, T; Suzuki, H; Hiroshima, Y; Matsuda, K; Hirai, S; Yamamoto, Y; Yamada, T; Sugaya, A; Kobayashi, M; Endo, S; Ishige, K; Nishina, T; Hyodo, I

2014-01-01

The survival benefit of second-line chemotherapy with docetaxel in platinum-refractory patients with advanced esophageal cancer (AEC) remains unclear. A retrospective analysis of AEC patients with Eastern Cooperative Oncology Group performance status (PS)≤2 was performed, and major organ functions were preserved, who determined to receive docetaxel or best supportive care (BSC) alone after failure of platinum-based chemotherapy. The post-progression survival (PPS), defined as survival time after disease progression following platinum-based chemotherapy, was analyzed by multivariate Cox regression analysis using factors identified as significant in univariate analysis of various 20 characteristics (age, sex, PS, primary tumor location, etc) including Glasgow prognostic score (GPS), which is a well-known prognostic factor in many malignant tumors. Sixty-six and 45 patients were determined to receive docetaxel and BSC between January 2007 and December 2011, respectively. The median PPS was 5.4 months (95% confidence interval [CI] 4.8-6.0) in the docetaxel group and 3.3 months (95% CI 2.5-4.0) in the BSC group (hazard ratio [HR] 0.56, 95% CI 0.38-0.84, P=0.005). Univariate analysis revealed six significant factors: treatment, PS, GPS, number of metastatic organs, liver metastasis, and bone metastasis. Multivariate analysis including these significant factors revealed three independent prognostic factors: docetaxel treatment (HR 0.62, 95% CI 0.39-0.99, P=0.043), better GPS (HR 0.61, 95% CI 0.46-0.81, P=0.001), and no bone metastasis (HR 0.31, 95% CI 0.15-0.68, P=0.003). There was a trend for PPS in favor of the docetaxel group compared with patients who refused docetaxel treatment in the BSC group (adjusted HR 0.61, 95% CI 0.29-1.29, P=0.20). Docetaxel treatment may have prolonged survival in platinum-refractory patients with AEC. © 2014 International Society for Diseases of the Esophagus.

Direct Tumor Microinjection and FDG-PET in Testing Drug Sensitivity in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma, Hodgkin Lymphoma, or Stage IV Breast Cancer

ClinicalTrials.gov

2018-03-28

Breast Adenocarcinoma; Recurrent Breast Carcinoma; Recurrent Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Nodal Marginal Zone Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Breast Cancer AJCC v6 and v7

50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate.

PubMed

Cavus, Idil; Widi, Gabriel A; Duckrow, Robert B; Zaveri, Hitten; Kennard, Jeremy T; Krystal, John; Spencer, Dennis D

2016-02-01

The effect of electrical stimulation on brain glutamate release in humans is unknown. Glutamate is elevated at baseline in the epileptogenic hippocampus of patients with refractory epilepsy, and increases during spontaneous seizures. We examined the effect of 50 Hz stimulation on glutamate release and its relationship to interictal levels in the hippocampus of patients with epilepsy. In addition, we measured basal and stimulated glutamate levels in a subset of these patients where stimulation elicited a seizure. Subjects (n = 10) were patients with medically refractory epilepsy who were undergoing intracranial electroencephalography (EEG) evaluation in an epilepsy monitoring unit. Electrical stimulation (50 Hz) was delivered through implanted hippocampal electrodes (n = 11), and microdialysate samples were collected every 2 min. Basal glutamate, changes in glutamate efflux with stimulation, and the relationships between peak stimulation-associated glutamate concentrations, basal zero-flow levels, and stimulated seizures were examined. Stimulation of epileptic hippocampi in patients with refractory epilepsy caused increases in glutamate efflux (p = 0.005, n = 10), and 4 of ten patients experienced brief stimulated seizures. Stimulation-induced increases in glutamate were not observed during the evoked seizures, but rather were related to the elevation in interictal basal glutamate (R(2) = 0.81, p = 0.001). The evoked-seizure group had lower basal glutamate levels than the no-seizure group (p = 0.04), with no stimulation-induced change in glutamate efflux (p = 0.47, n = 4). Conversely, increased glutamate was observed following stimulation in the no-seizure group (p = 0.005, n = 7). Subjects with an atrophic hippocampus had higher basal glutamate levels (p = 0.03, n = 7) and higher stimulation-induced glutamate efflux. Electrical stimulation of the epileptic hippocampus either increased extracellular glutamate efflux or induced seizures. The magnitude of stimulated glutamate increase was related to elevation in basal interictal glutamate, suggesting a common mechanism, possibly impaired glutamate metabolism. Divergent mechanisms may exist for seizure induction and increased glutamate in patients with epilepsy. These data highlight the potential risk of 50 Hz stimulation in patients with epilepsy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Matched unrelated donor allogeneic transplantation provides comparable long-term outcome to HLA-identical sibling transplantation in relapsed diffuse large B-cell lymphoma.

PubMed

Avivi, I; Canals, C; Vernant, J-P; Wulf, G; Nagler, A; Hermine, O; Petersen, E; Yakoub-Agha, I; Craddock, C; Schattenberg, A; Niederwieser, D; Thomson, K; Blaise, D; Attal, M; Pfreundschuh, M; Passweg, J; Russell, N; Dreger, P; Sureda, A

2014-05-01

The objective of this retrospective analysis was to compare outcomes of patients with diffuse large B-cell lymphoma (DLBCL) who received either a matched sibling (sib) or an unrelated donor (URD) allogeneic hematopoietic cell transplantation (allo-HCT). Long-term outcome of 172 DLBCL patients receiving URD-HCT between 2000 and 2007 and reported to the European Group for Blood and Marrow Transplantation, was compared with that of 301 subjects, allografted from sib-HCT. With a median follow-up of 45 months, 3-year PFS approached 35% for both groups; overall survival (OS) was 42% for sib-HCT versus 37% for URD (NS). Multivariate analyses confirmed that donor type was not associated with differences in non-relapse mortality (NRM), relapse rate (RR), PFS or OS. Poor performance status (PS) and refractory disease adversely affected PFS and OS. Prior auto-SCT and multiple previous therapies predicted for shorter PFS. NRM was adversely affected by older age (⩾50 years), poor PS and refractory disease, and RR by time from diagnosis to allo-HCT of <36 months, prior auto-SCT, refractory disease, poor PS and in vivo T-cell depletion with alemtuzumab. This large study shows for the first time that URD-HCT is not inferior to sib-HCT, providing a reasonable therapeutic approach for DLBCL patients, having no HLA-identical sibling available.

Evolution of Morphological and Physical Properties of Laboratory Interstellar Organic Residues with Ultraviolet Irradiation

NASA Astrophysics Data System (ADS)

Piani, L.; Tachibana, S.; Hama, T.; Tanaka, H.; Endo, Y.; Sugawara, I.; Dessimoulie, L.; Kimura, Y.; Miyake, A.; Matsuno, J.; Tsuchiyama, A.; Fujita, K.; Nakatsubo, S.; Fukushi, H.; Mori, S.; Chigai, T.; Yurimoto, H.; Kouchi, A.

2017-03-01

Refractory organic compounds formed in molecular clouds are among the building blocks of the solar system objects and could be the precursors of organic matter found in primitive meteorites and cometary materials. However, little is known about the evolutionary pathways of molecular cloud organics from dense molecular clouds to planetary systems. In this study, we focus on the evolution of the morphological and viscoelastic properties of molecular cloud refractory organic matter. We found that the organic residue, experimentally synthesized at ˜10 K from UV-irradiated H2O-CH3OH-NH3 ice, changed significantly in terms of its nanometer- to micrometer-scale morphology and viscoelastic properties after UV irradiation at room temperature. The dose of this irradiation was equivalent to that experienced after short residence in diffuse clouds (≤104 years) or irradiation in outer protoplanetary disks. The irradiated organic residues became highly porous and more rigid and formed amorphous nanospherules. These nanospherules are morphologically similar to organic nanoglobules observed in the least-altered chondrites, chondritic porous interplanetary dust particles, and cometary samples, suggesting that irradiation of refractory organics could be a possible formation pathway for such nanoglobules. The storage modulus (elasticity) of photo-irradiated organic residues is ˜100 MPa irrespective of vibrational frequency, a value that is lower than the storage moduli of minerals and ice. Dust grains coated with such irradiated organics would therefore stick together efficiently, but growth to larger grains might be suppressed due to an increase in aggregate brittleness caused by the strong connections between grains.

Evolution of Morphological and Physical Properties of Laboratory Interstellar Organic Residues with Ultraviolet Irradiation

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

Piani, L.; Tachibana, S.; Endo, Y.

Refractory organic compounds formed in molecular clouds are among the building blocks of the solar system objects and could be the precursors of organic matter found in primitive meteorites and cometary materials. However, little is known about the evolutionary pathways of molecular cloud organics from dense molecular clouds to planetary systems. In this study, we focus on the evolution of the morphological and viscoelastic properties of molecular cloud refractory organic matter. We found that the organic residue, experimentally synthesized at ∼10 K from UV-irradiated H{sub 2}O-CH{sub 3}OH-NH{sub 3} ice, changed significantly in terms of its nanometer- to micrometer-scale morphology andmore » viscoelastic properties after UV irradiation at room temperature. The dose of this irradiation was equivalent to that experienced after short residence in diffuse clouds (≤10{sup 4} years) or irradiation in outer protoplanetary disks. The irradiated organic residues became highly porous and more rigid and formed amorphous nanospherules. These nanospherules are morphologically similar to organic nanoglobules observed in the least-altered chondrites, chondritic porous interplanetary dust particles, and cometary samples, suggesting that irradiation of refractory organics could be a possible formation pathway for such nanoglobules. The storage modulus (elasticity) of photo-irradiated organic residues is ∼100 MPa irrespective of vibrational frequency, a value that is lower than the storage moduli of minerals and ice. Dust grains coated with such irradiated organics would therefore stick together efficiently, but growth to larger grains might be suppressed due to an increase in aggregate brittleness caused by the strong connections between grains.« less

Adjustable high emittance gap filler. [reentry shielding for space shuttle vehicles

NASA Technical Reports Server (NTRS)

Leiser, D. B.; Stewart, D. A.; Smith, M.; Estrella, C. A.; Goldstein, H. E. (Inventor)

1981-01-01

A flexible, adjustable refractory filler is disclosed for filling gaps between ceramic tiles forming the heat shield of a space shuttle vehicle, to protect its aluminum skin during atmospheric reentry. The easily installed and replaced filler consists essentially of a strip of ceramic cloth coated, at least along both its longitudinal edges with a room temperature vulcanizable silicone rubber compound with a high emittance colored pigment. The filler may have one or more layers as the gap width requires. Preferred materials are basket weave aluminoborosilicate cloth, and a rubber compounded with silicon tetraboride as the emittance agent and finely divided borosilicate glass containing about 7.5% B2O3 as high temperature binder. The filler cloth strip or tape is cut to proper width and length, inserted into the gap, and fastened with previously applied drops of silicone rubber adhesive.

Steroid eye drop treatment (difluprednate ophthalmic emulsion) is effective in reducing refractory diabetic macular edema.

PubMed

Nakano, Sakiko; Yamamoto, Teiko; Kirii, Eriko; Abe, Sachi; Yamashita, Hidetoshi

2010-06-01

To evaluate the efficacy of treatment of refractory diabetic macular edema (DME) after vitrectomy with difluprednate ophthalmic emulsion 0.05% (Durezol(TM)), and to compare this treatment with sub-Tenon's injection of triamcinolone (STTA). This study enrolled patients with refractory diabetic macular edema that persisted despite pars plana vitrectomy in our clinic. In all subjects, more than 3 months had passed since prior treatment. Eleven eyes in ten subjects were treated with STTA (STTA group), and 11 eyes in seven subjects were treated with difluprednate ophthalmic emulsion 0.05% (Durezol(TM), Sirion Therapeutics Inc., USA) 4 times daily for the first month and then twice daily for 2 months (eye drop group). In the eye drop group, mean VA (+/- SD) was 0.67 +/- 0.35 logMAR and mean retinal thickness was 500.6 +/- 207.7 mum at baseline. After 3 months of treatment, mean VA was 0.67 +/- 0.29 and mean retinal thickness had decreased to 341.2 +/- 194.8 mum. The mean minimum value of RT during the treatment period was 300.6 +/- 123.2 mum, and significantly lower than that at baseline (Mann-Whitney U test: P = 0.003). In the STTA group, mean VA (+/- SD) was 0.67 +/- 0.35 logMAR, and mean retinal thickness was 543.3 +/- 132.6 mum at baseline. After 3 months of treatment, mean VA was 0.49 +/- 0.67, and mean retinal thickness had decreased to 378.6 +/- 135 mum. The mean minimum value of RT during the treatment period was 349.9 +/- 113.8 mum, and significantly lower than at baseline (Mann-Whitney U test: P = 0.003). The rate of effective improvement in RT did not differ between the eye drop group (73%) and STTA group (84%) (Fisher's exact test: P = 1). Comparable improvements of retinal thickness were observed in the STTA and eye drop groups. Instillation of difluprednate ophthalmic emulsion 0.05% is a safe and effective treatment that does not require surgical intervention and does not produce severe side-effects.

The Use Of Phosphates To Reduce Slag Penetration In Cr203-Based Refractories

DOEpatents

Kwong, Kyei-Sing; Dogan, Cynthia P.; Bennett, James P.; Chinn, Richard E.; Petty, Arthur V.

2004-11-09

A high-chromium refractory material that provides improved resistance to coal slag penetration is presented. The refractory mixture comprises a blend of chromium oxide, aluminum oxide and phosphates. The refractory mixture may be blended with an aggregate and cured. In addition a phosphorous oxide may be blended with chromium oxide and aluminum oxide and additionally an aggregate. The refractory mixture reduces the rate of coal slag penetration into the surface of the cured refractory.

Pembrolizumab in Treating Younger Patients With Recurrent, Progressive, or Refractory High-Grade Gliomas, Diffuse Intrinsic Pontine Gliomas, Hypermutated Brain Tumors, Ependymoma or Medulloblastoma

ClinicalTrials.gov

2018-06-28

Constitutional Mismatch Repair Deficiency Syndrome; Lynch Syndrome; Malignant Glioma; Progressive Ependymoma; Progressive Medulloblastoma; Recurrent Brain Neoplasm; Recurrent Childhood Ependymoma; Recurrent Diffuse Intrinsic Pontine Glioma; Recurrent Medulloblastoma; Refractory Brain Neoplasm; Refractory Diffuse Intrinsic Pontine Glioma; Refractory Ependymoma; Refractory Medulloblastoma

Isotopic Dichotomy among Meteorites and Its Bearing on the Protoplanetary Disk

NASA Astrophysics Data System (ADS)

Scott, Edward R. D.; Krot, Alexander N.; Sanders, Ian S.

2018-02-01

Whole rock Δ17O and nucleosynthetic isotopic variations for chromium, titanium, nickel, and molybdenum in meteorites define two isotopically distinct populations: carbonaceous chondrites (CCs) and some achondrites, pallasites, and irons in one and all other chondrites and differentiated meteorites in the other. Since differentiated bodies accreted 1–3 Myr before the chondrites, the isotopic dichotomy cannot be attributed to temporal variations in the disk. Instead, the two populations were most likely separated in space, plausibly by proto-Jupiter. Formation of CCs outside Jupiter could account for their characteristic chemical and isotopic composition. The abundance of refractory inclusions in CCs can be explained if they were ejected by disk winds from near the Sun to the disk periphery where they spiraled inward due to gas drag. Once proto-Jupiter reached 10–20 M ⊕, its external pressure bump could have prevented millimeter- and centimeter-sized particles from reaching the inner disk. This scenario would account for the enrichment in CCs of refractory inclusions, refractory elements, and water. Chondrules in CCs show wide ranges in Δ17O as they formed in the presence of abundant 16O-rich refractory grains and 16O-poor ice particles. Chondrules in other chondrites (ordinary, E, R, and K groups) show relatively uniform, near-zero Δ17O values as refractory inclusions and ice were much less abundant in the inner solar system. The two populations were plausibly mixed together by the Grand Tack when Jupiter and Saturn migrated inward emptying and then repopulating the asteroid belt with roughly equal masses of planetesimals from inside and outside Jupiter’s orbit (S- and C-type asteroids).

Olanzapine is effective for refractory chemotherapy-induced nausea and vomiting irrespective of chemotherapy emetogenicity.

PubMed

Vig, Sierra; Seibert, Laurel; Green, Myke R

2014-01-01

The role of olanzapine added to a dopamine antagonist and benzodiazepine for the treatment of refractory chemotherapy-induced nausea and vomiting (CINV) is incompletely characterized in all levels of chemotherapy emetogenicity. This retrospective study evaluated the efficacy of the addition of olanzapine in adults experiencing refractory CINV stratified by chemotherapy emetogenicity. Thirty-three adults who experienced CINV refractory to guideline-recommended prophylaxis and breakthrough antiemetics (dopamine antagonists and benzodiazepines) and received at least one dose of olanzapine 5-10 mg per os were evaluated. Failure was defined as >5 emesis events in 24 h or more than 10 cumulative doses of rescue antiemetics following first olanzapine dose per treatment cycle. Post hoc analyses investigated variables impacting olanzapine efficacy. The addition of olanzapine demonstrated an overall success rate of 70 %. This success rate did not differ between chemotherapy regimens of high versus low-to-moderate emetogenicity (p = 0.79), prophylaxis with serotonin antagonist plus corticosteroid and aprepitant versus serotonin antagonist alone (p = 0.77), or age over 50 versus ≤50 years (p > 0.99). A trend toward greater benefit was seen in women (p = 0.08). The addition of olanzapine to a dopamine antagonist and benzodiazepine demonstrated high efficacy rates for refractory CINV irrespective of chemotherapy emetogenicity. The high success rates among all groups suggests that incomplete resolution of CINV with prophylactic serotonin antagonists and breakthrough dopamine antagonists plus benzodiazepine may benefit from the addition of olanzapine regardless of gender, degree of chemotherapy emetogenicity, number of prophylactic antiemetics, or age. The trend toward greater control of emesis in women merits further investigation.

A one-year prospective study of refractory status epilepticus in Modena, Italy.

PubMed

Giovannini, Giada; Monti, Giulia; Polisi, Michela M; Mirandola, Laura; Marudi, Andrea; Pinelli, Giovanni; Valzania, Franco; Girardis, Massimo; Nichelli, Paolo F; Meletti, Stefano

2015-08-01

Refractory status epilepticus (RSE) is a particular critical condition characterized by seizures that continue despite the use of first- and second-line therapies and by high mortality. To date, only one prospective study investigated clinical features and prognostic factors in RSE. In this study, we performed a one-year prospective survey to identify clinical features, outcomes, and variables associated with the development of RSE in the adolescent and adult population of Modena, northern Italy. We observed 83 episodes of SE in 83 patients. In 31% of the cases, third-line therapy (anesthetic drug) was needed. Among this group, 14% resolved and were classified as RSE, while, in 17%, seizures recurred at withdrawal of anesthetics and were classified as super-RSE. The development of RSE/super-RSE was associated with a stuporous/comatose state at presentation and with the absence of a previous history of epilepsy. Refractory status epilepticus/super-refractory status epilepticus showed a worse outcome compared with responsive SE: 54% versus 21% for 30-day mortality; 19% versus 56% for a return to baseline condition. This prospective study confirms stupor/coma at onset as a relevant clinical factor associated with SE refractoriness. We observed a rate of RSE comparable with previous reports, with high mortality and morbidity. Mortality in the observed RSE was higher than in previous studies; this result is probably related to the low rate of a previous epilepsy history in our population that reflects a high incidence of acute symptomatic etiologies, especially the inclusion of patients with postanoxic SE who have a bad prognosis per se. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

Lacosamide as adjunctive therapy in refractory epilepsy in adults: a systematic review.

PubMed

Paquette, Vanessa; Culley, Celia; Greanya, Erica D; Ensom, Mary H H

2015-02-01

To review the evidence for efficacy and safety of lacosamide in adult patients with refractory epilepsy and refractory status epilepticus (RSE). A systematic literature search of MEDLINE, PubMed, EMBASE, IPA, Google and Google Scholar (through October 2014) was performed. Fourteen studies assessing lacosamide in 3509 refractory epilepsy patients were included. In 3 RCTs, more patients had at least 50% reduction in seizure frequency with lacosamide compared to placebo with 38.3-41.1%, 38.1-41.2%, and 18.3-25.8%, in the 400 mg/day, 600 mg/day, and placebo groups, respectively. In non-comparative trials, 18-69% of patients achieved at least 50% reduction in seizure frequency, and 1.7-26.2% achieved seizure freedom. Non-responders were documented in two trials, with 26.2-34% having no response. Thirteen studies assessing lacosamide in 390 RSE patients were included. When assessing lacosamide's ability to terminate RSE, one comparative cohort study found no improvement in SE duration or seizure control with addition of lacosamide. Another study documented no difference compared to use of phenytoin. Eleven descriptive studies using lacosamide as add-on RSE therapy revealed seizure termination rates of 0-100% (median 64.7%). In all patients receiving lacosamide, dizziness (21.8%), vision disturbances (10.4%), drowsiness (7.4%), headache (7.0%), nausea (6.5%), and coordination problems (5.8%) were the most common adverse effects. Based on evidence to date, adjunctive lacosamide is a treatment option to reduce seizure frequency in patients with refractory epilepsy and terminate seizures in patients with RSE. The safety information summary can be used to advise patients of potential adverse effects. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Phase I/II Trial and Pharmacokinetic Study of Cixutumumab in Pediatric Patients With Refractory Solid Tumors and Ewing Sarcoma: A Report From the Children's Oncology Group

PubMed Central

Malempati, Suman; Weigel, Brenda; Ingle, Ashish M.; Ahern, Charlotte H.; Carroll, Julie M.; Roberts, Charles T.; Reid, Joel M.; Schmechel, Stephen; Voss, Stephan D.; Cho, Steven Y.; Chen, Helen X.; Krailo, Mark D.; Adamson, Peter C.; Blaney, Susan M.

2012-01-01

Purpose A phase I/II study of cixutumumab (IMC-A12) in children with refractory solid tumors was conducted. This study was designed to assess the toxicities, pharmacokinetics, and pharmacodynamics of cixutumumab in children to determine a recommended phase II dose and to assess antitumor activity in Ewing sarcoma (ES). Patients and Methods Pediatric patients with relapsed or refractory solid tumors were treated with cixutumumab as a 1-hour intravenous infusion once per week. Two dose levels—6 and 9 mg/kg—were evaluated using a standard three-plus-three cohort design. Patients with refractory ES were treated in an expanded phase II cohort at each dose level. Results Forty-seven eligible patients with a median age of 15 years (range, 4 to 28 years) were enrolled. Twelve patients were treated in the dose-finding phase. Hematologic and nonhematologic toxicities were generally mild and infrequent. Dose-limiting toxicities included grade 4 thrombocytopenia at 6 mg/kg and grade 3 dehydration at 9 mg/kg. Mean trough concentration (± standard deviation) at 9 mg/kg was 106 ± 57 μg/mL, which exceeded the effective trough concentration of 60 μg/mL observed in xenograft models. Three patients with ES had confirmed partial responses: one of 10 at 6 mg/kg and two of 20 at 9 mg/kg. Serum insulin-like growth factor I (IGF-I) levels consistently increased after one dose of cixutumumab. Tumor IGF-I receptor expression by immunohistochemistry did not correlate with response in patients with ES. Conclusion Cixutumumab is well tolerated in children with refractory solid tumors. The recommended phase II dose is 9 mg/kg. Limited single-agent activity of cixutumumab was seen in ES. PMID:22184397

Enhanced external counterpulsation in patients with refractory angina pectoris: a pilot study with six months follow-up regarding physical capacity and health-related quality of life.

PubMed

Wu, Eline; Mårtensson, Jan; Broström, Anders

2013-10-01

Refractory angina pectoris (AP) is a persistent, painful condition characterized by angina caused by coronary insufficiency in the presence of coronary artery disease. It has been emphasized that there are possible underlying neuropathophysiological mechanisms for refractory AP but chronic ischemia is still considered to be the main problem. These patients suffer from severe AP and cannot be controlled by a combination of pharmacological therapies, angioplasty or coronary bypass surgery. AP has a negative impact on quality of life and daily life. Enhanced external counterpulsation (EECP) is a therapeutic option for these patients. The aim of this study was to evaluate EECP after six months regarding physical capacity and health-related quality of life (HRQoL) in patients with refractory AP. This was a study with single case research experimental design involving 34 patients treated with EECP. Six minute walk test (6MWT), functional class with Canadian Cardiological Society (CCS) classification and self-reported HRQoL questionnaires as Short Form 36 (SF-36) were collected at baseline and after treatment. CCS class and SF-36 were repeated at six months follow-up. Patients enhanced walk distance on average by 29 m after EECP (p<0.01). CCS class also improved (p<0.001) and persisted at six months follow-up (p<0.001). HRQoL improved significantly and the effects were maintained at follow-up after the treatment. Patients with refractory AP receive beneficial effects from EECP both in physical capacity and HRQoL. As other treatment options for this patient group are scarce, EECP should be offered to improve physical health and HRQoL in these patients.

Lenvatinib in Advanced Radioiodine-Refractory Thyroid Cancer - A Retrospective Analysis of the Swiss Lenvatinib Named Patient Program.

PubMed

Balmelli, Catharina; Railic, Nikola; Siano, Marco; Feuerlein, Kristin; Cathomas, Richard; Cristina, Valerie; Güthner, Christiane; Zimmermann, Stefan; Weidner, Sabine; Pless, Miklos; Stenner, Frank; Rothschild, Sacha I

2018-01-01

Purpose: Differentiated thyroid cancer (DTC) accounts for approximately 95% of thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has very limited efficacy and is associated with substantial toxicity. With increasing knowledge of the molecular pathogenesis of DTC, novel targeted therapies have been developed. Lenvatinib is a tyrosine kinase inhibitor (TKI) with promising clinical activity based on the randomized phase III SELECT trial. In Switzerland, a Named Patient Program (NPP) was installed to bridge the time gap to Swissmedic approval. Here, we report the results from the Swiss Lenvatinib NPP including patients with metastatic RAI-refractory DTC. Methods: Main inclusion criteria for the Swiss NPP were RAI-refractory DTC, documented disease progression, Eastern Cooperative Oncology Group (ECOG) performance status 0-3. The number of previous therapies was not limited. The Swiss Lenvatinib NPP was initiated in June 2014 and was closed in October 2015 with the approval of the drug. Results: Between June 2014 and October 2015, 13 patients with a median age of 72 years have been enrolled. Most patients (69%) had at least one prior systemic therapy, mainly sorafenib. 31% of patients showed a PR and 31% SD. Median progression free survival was 7.2 months and the median overall survival was 22.7 months. Dose reduction due to adverse events was necessary in 7 patients (53%). At the time of analysis 6 patients (47%) were still on treatment with a median time on treatment of 9.98 months. Conclusions: Our results show that lenvatinib has reasonable clinical activity in unselected patients with RAI-refractory thyroid cancer with nearly two-third of patients showing clinical benefit. The toxicity profile of lenvatinib is manageable.

Lenvatinib in Advanced Radioiodine-Refractory Thyroid Cancer - A Retrospective Analysis of the Swiss Lenvatinib Named Patient Program

PubMed Central

Balmelli, Catharina; Railic, Nikola; Siano, Marco; Feuerlein, Kristin; Cathomas, Richard; Cristina, Valerie; Güthner, Christiane; Zimmermann, Stefan; Weidner, Sabine; Pless, Miklos; Stenner, Frank; Rothschild, Sacha I.

2018-01-01

Purpose:Differentiated thyroid cancer (DTC) accounts for approximately 95% of thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has very limited efficacy and is associated with substantial toxicity. With increasing knowledge of the molecular pathogenesis of DTC, novel targeted therapies have been developed. Lenvatinib is a tyrosine kinase inhibitor (TKI) with promising clinical activity based on the randomized phase III SELECT trial. In Switzerland, a Named Patient Program (NPP) was installed to bridge the time gap to Swissmedic approval. Here, we report the results from the Swiss Lenvatinib NPP including patients with metastatic RAI-refractory DTC. Methods:Main inclusion criteria for the Swiss NPP were RAI-refractory DTC, documented disease progression, Eastern Cooperative Oncology Group (ECOG) performance status 0-3. The number of previous therapies was not limited. The Swiss Lenvatinib NPP was initiated in June 2014 and was closed in October 2015 with the approval of the drug. Results:Between June 2014 and October 2015, 13 patients with a median age of 72 years have been enrolled. Most patients (69%) had at least one prior systemic therapy, mainly sorafenib. 31% of patients showed a PR and 31% SD. Median progression free survival was 7.2 months and the median overall survival was 22.7 months. Dose reduction due to adverse events was necessary in 7 patients (53%). At the time of analysis 6 patients (47%) were still on treatment with a median time on treatment of 9.98 months. Conclusions:Our results show that lenvatinib has reasonable clinical activity in unselected patients with RAI-refractory thyroid cancer with nearly two-third of patients showing clinical benefit. The toxicity profile of lenvatinib is manageable. PMID:29344270

ICE CHEMISTRY ON OUTER SOLAR SYSTEM BODIES: ELECTRON RADIOLYSIS OF N{sub 2}-, CH{sub 4}-, AND CO-CONTAINING ICES

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

Materese, Christopher K.; Cruikshank, Dale P.; Sandford, Scott A.

Radiation processing of the surface ices of outer Solar System bodies may be an important process for the production of complex chemical species. The refractory materials resulting from radiation processing of known ices are thought to impart to them a red or brown color, as perceived in the visible spectral region. In this work, we analyzed the refractory materials produced from the 1.2-keV electron bombardment of low-temperature N{sub 2}-, CH{sub 4}-, and CO-containing ices (100:1:1), which simulates the radiation from the secondary electrons produced by cosmic ray bombardment of the surface ices of Pluto. Despite starting with extremely simple icesmore » dominated by N{sub 2}, electron irradiation processing results in the production of refractory material with complex oxygen- and nitrogen-bearing organic molecules. These refractory materials were studied at room temperature using multiple analytical techniques including Fourier-transform infrared spectroscopy, X-ray absorption near-edge structure (XANES) spectroscopy, and gas chromatography coupled with mass spectrometry (GC-MS). Infrared spectra of the refractory material suggest the presence of alcohols, carboxylic acids, ketones, aldehydes, amines, and nitriles. XANES spectra of the material indicate the presence of carboxyl groups, amides, urea, and nitriles, and are thus consistent with the IR data. Atomic abundance ratios for the bulk composition of these residues from XANES analysis show that the organic residues are extremely N-rich, having ratios of N/C ∼ 0.9 and O/C ∼ 0.2. Finally, GC-MS data reveal that the residues contain urea as well as numerous carboxylic acids, some of which are of interest for prebiotic and biological chemistries.« less

Ice Chemistry on Outer Solar System Bodies: Electron Radiolysis of N2-, CH4-, and CO-Containing Ices

NASA Astrophysics Data System (ADS)

Materese, Christopher K.; Cruikshank, Dale P.; Sandford, Scott A.; Imanaka, Hiroshi; Nuevo, Michel

2015-10-01

Radiation processing of the surface ices of outer Solar System bodies may be an important process for the production of complex chemical species. The refractory materials resulting from radiation processing of known ices are thought to impart to them a red or brown color, as perceived in the visible spectral region. In this work, we analyzed the refractory materials produced from the 1.2-keV electron bombardment of low-temperature N2-, CH4-, and CO-containing ices (100:1:1), which simulates the radiation from the secondary electrons produced by cosmic ray bombardment of the surface ices of Pluto. Despite starting with extremely simple ices dominated by N2, electron irradiation processing results in the production of refractory material with complex oxygen- and nitrogen-bearing organic molecules. These refractory materials were studied at room temperature using multiple analytical techniques including Fourier-transform infrared spectroscopy, X-ray absorption near-edge structure (XANES) spectroscopy, and gas chromatography coupled with mass spectrometry (GC-MS). Infrared spectra of the refractory material suggest the presence of alcohols, carboxylic acids, ketones, aldehydes, amines, and nitriles. XANES spectra of the material indicate the presence of carboxyl groups, amides, urea, and nitriles, and are thus consistent with the IR data. Atomic abundance ratios for the bulk composition of these residues from XANES analysis show that the organic residues are extremely N-rich, having ratios of N/C ∼ 0.9 and O/C ∼ 0.2. Finally, GC-MS data reveal that the residues contain urea as well as numerous carboxylic acids, some of which are of interest for prebiotic and biological chemistries.

The efficacy of Ahmed glaucoma valve drainage devices in cases of adult refractory glaucoma in Indian eyes

PubMed Central

Parihar, Jitendra K S; Vats, Devendra P; Maggon, Rakesh; Mathur, Vijay; Singh, Anirudh; Mishra, Sanjay K

2009-01-01

Aim: To evaluate the efficacy of Ahmed glaucoma valve (AGV) drainage devices in cases of adult refractory glaucoma in Indian eyes. Settings and Design: Retrospective interventional case series study. Materials and Methods: Fifty two eyes of 32 patients of refractory glaucoma in the age group of 35 to 60 years who underwent AGV implantation with or without concomitant procedures from January 2003 to Jan 2007 were studied. Of these, 46 eyes (88%) had undergone filtering surgery earlier whereas remaining eyes underwent primary AGV implantation following failure of maximal medical therapy. The follow up ranged between 12 months to 48 months Results: Eighteen eyes (35%) had undergone phacoemulsification with AGV implantation, penetrating keratoplasty (PK) with AGV and intraocular lens (IOL) implantation in 13 eyes (25%), AGV over preexisting IOL in eight eyes (15%). AGV implantation alone was done in six (11%) eyes. Anterior chamber (AC) reconstruction with secondary IOL and AGV was performed in the remaining eyes. The mean intra ocular pressure (IOP) decreased from 36.3 ± 15.7 mm Hg to 19.6 ± 9.2 mm Hg. Complete success as per criteria was achieved in 46 eyes (88%). None of the eyes had failure to maintain IOP control following AGV. Conclusion: The AGV resulted in effective and sustained control of IOP in cases of adult refractory glaucoma in intermediate follow up. PMID:19700871

[State of the art treatment of progressive or refractory multiple myeloma].

PubMed

Schmidt-Wolf, I G H; Straka, C; Scheid, C; Einsele, H; Goldschmidt, H; Engelhardt, M

2014-10-01

Multiple myeloma (MM) is with an incidence of 4-6/100 000 inhabitants a fairly frequent malignancy of B cells. The incidence increases markedly with age. In this review changes in the treatment of relapsed / refractory myeloma during the last decade have been analysed. The present standard of care in the progressive or refractory myeloma was elaborated by the working group "Refractory Multiple Myeloma" using an extensive literature search for studies published between 2003 and 2013. Outside of clinical trials, high-dose therapy with stem cell transplantation is recommended in fit patients up to 75 years without significant comorbidities. Ongoing studies address the question about the least toxic and the most effective treatment. Therefore, inclusion of patients in therapeutic trials and use of novel agent combinations is highly recommended, e.g. with 3(rd) generation-IMIDs (pomalidomide), new proteasome inhibitors, such as carfilzomib, ixazomib or oprozomib, antibodies, such as elotuzumab, daratumumab or SAR650984, siltuximab, tabalumab, denosumab, romosozumab, BTK-, HSP-inhibitors and other innovative phase I/II agents. Based on new insights in the pathogenesis of the disease, treatment options for MM have changed significantly in recent years. There is a significantly larger treatment diversity, i.e. more MM-active agents and combinations are available today. Even with relapsed MM, patients with the disease often live longer and have fewer complications. © Georg Thieme Verlag KG Stuttgart · New York.

Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer

ClinicalTrials.gov

2018-01-17

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Aggressive Non-Hodgkin Lymphoma; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Indolent Non-Hodgkin Lymphoma; Lymphoma; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Recurrent Chronic Lymphocytic Leukemia; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Follicular Lymphoma; Refractory Hodgkin Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Small Lymphocytic Lymphoma; T-Cell Non-Hodgkin Lymphoma

Effect of Persian Medicine Remedy on Chemotherapy Induced Nausea and Vomiting in Breast Cancer: A Double Blind, Randomized, Crossover Clinical Trial

PubMed Central

Nazari, Mohammad; Taghizadeh, Ali; Bazzaz, Mojtaba Mousavi; Rakhshandeh, Hassan; Shokri, Sadegh

2017-01-01

Background Chemotherapy induced nausea and vomiting (CINV) is a side effect, and has negative effect on quality of life and continuation of chemotherapy. Despite new regimen and drugs, the problems still remain and standard guidelines, effective treatment and supportive care for refractory CINV are still not yet established. Persian medicine, the old Iranian medical school, offer Persumac (prepared from Rhus Coriaria and Bunium Persicum Boiss). Objective The specific objectives were to assess the effect of Persumac on the number and severity of nausea and vomiting in refractory CINV in acute and delayed phase. Methods This randomized, double blind, crossover clinical trial study was carried out on 93 patients with breast cancer and refractory CINV, who received outpatient high emetogenic chemotherapy in Imam Reza hospital, Mashhad, Iran from October 2015 to May 2016. The study has three stages: in stage I patients received a questionaire and completed it after chemotherapy. In stage II they were randomly divided into intervention group with Persumac and control group with placebo (lactose were used). In stage III, wash out and crossover was conducted. Both groups in all stages received standard antiemetic therapy for CINV. The following were set as the inclusion criteria of the study: female, Age ≥18 years, clinical diagnosis of breast cancer, history of refractory CINV, normal blood tests and at least three courses of chemotherapy remaining. Exclusion criteria of this study were: Total or upper abdominal radiation therapy along with chemotherapy, drugs/therapy for nausea and vomiting not prescribed in this study, hypersensitivity to Sumac or Bunium Persicum, use of sumac and Bunium Persicum in seven days prior to the intervention, clinical diagnosis of digestion disorders, non-chemotherapy induced nausea and vomiting, milk allergy, loss of two consecutive or three intermittent doses of Persumac or placebo. Outcomes were gathered by Persian questionnaire. Number and severity of nausea and vomiting was measured with a self-reporting tool; visual analog scale. Results Demographic data and other characters in both groups have no significant diffrence. Eighty of 93 eligible patients in stage I completed the study and in stage II, eleven declined participation for stage III (crossover). P value of carry over, period and treatment effects demonstrated that they had not affected the results before and after crossover. The mean severity of nausea in acute phase was in stage I: 4.83 ± 1.40, stage II: 4.54 ± 2.0 and stage III: 4.15 ± 0.92 in sequence AB (first Persumac and then placebo in crossover), and in sequence BA (first placebo and then Persumac in crossover) was respectively 4.83 ± 1.40, 4.54 ± 2.0, 4.15 ± 0.92 with p value of carry over effect: 0.03 and period effect: 0.22. Except for severity of nausea in acute phase, the mean number and severity of nausea and vomiting scores significantly decreased in acute and delayed phase of CINV. Conclusion Persumac may control the refractory CINV. The implicable and clinical importance of this research is that another option exists for refractory CINV. Higher doses, different cancers, patients with more various features, and more complete methodology and tools can provide appropriate designs for new research on this topic. Trial registration This trial was registered at the Clinical Trials.gov ID: NCT02787707. Funding This study is part of a Ph.D. thesis and under grant; No: 930735 of Research Chancellery of MUMS. PMID:28243404

Differentiation Therapy With Decitabine in Treating Patients With Myelodysplastic Syndrome

ClinicalTrials.gov

2013-02-25

Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Thrombocytopenia

Clinical follow-up after cessation of chronic electrical neuromodulation in patients with severe coronary artery disease: a prospective randomized controlled study on putative involvement of sympathetic activity.

PubMed

Jessurun, G A; DeJongste, M J; Hautvast, R W; Tio, R A; Brouwer, J; van Lelieveld, S; Crijns, H J

1999-10-01

The present study assessed the reoccurrence of myocardial ischemia after withholding electrical neurostimulation. After randomization, in the study or withdrawal group, spinal cord stimulation (SCS) was set active during the first 4 weeks, followed by 4 weeks of withholding stimulation. In the control group, SCS was switched off during 4 weeks before the end of the study. The control group had no crossover period. Measurements were done at baseline, then after 4 and 8 weeks. The first periods at 4 weeks of each sequence of both groups were compared. In addition, a comparison of clinical variables was performed between the study group 4 weeks after withholding stimulation and the control group 4 weeks following randomization. A total number of 24 patients with refractory angina and an implanted spinal cord stimulator were included in the study (n = 12) and control group. Angina pectoris complaints, nitroglycerin intake, ischemia, and heart rate variability using 48-hour ambulatory electrocardiographic monitoring were assessed. In addition, neurohormonal status and symptom-limited aerobic capacity were evaluated. There was no increase of anginal complaints or ischemia after withholding stimulation. Neurohormonal levels and aerobic capacity were not altered. We conclude that there is no adverse clinical rebound phenomenon after withholding neurostimulation in patients with refractory angina pectoris.

Is posterior synovial plica excision necessary for refractory lateral epicondylitis of the elbow?

PubMed

Rhyou, In Hyeok; Kim, Kang Wook

2013-01-01

Arthroscopic treatments for lateral epicondylitis including débridement of the extensor carpi radialis brevis (ECRB) origin (Baker technique) or resection of the radiocapitellar synovial plica reportedly improve symptoms. However the etiology of the disease and the role of the plica remain unclear. We asked if posterior radiocapitellar synovial plica excision made any additional improvement in pain or function after arthroscopic ECRB release. We retrospectively reviewed 38 patients who had arthroscopic treatment for refractory lateral epicondylitis between November 2003 and October 2009. Twenty patients (Group A) underwent the Baker technique and 18 patients (Group B) underwent a combination of the Baker technique and posterior synovial plica excision. The minimum followup was 36 months (mean, 46 months; range, 36-72 months) for Group A and 25 months (mean, 30 months; range, 25-36 months) for Group B. Postoperatively we obtained VAS pain and DASH scores for each group. Two years postoperatively, we found no differences in the VAS pain score or DASH: the mean VAS pain scores were 0.3 points in Group A and 0.4 points in Group B, and the DASH scores were 5.1 points and 6.1 points respectively. The addition of débridement of the posterior synovial fold did not appear to enhance either pain relief or function compared with the classic Baker technique without decortication.

Clinical Investigation of Refractory Chronic Subdural Hematoma: A Comparison of Clinical Factors Between Single and Repeated Recurrences.

PubMed

Matsumoto, Hiroaki; Hanayama, Hiroaki; Okada, Takashi; Sakurai, Yasuo; Minami, Hiroaki; Masuda, Atsushi; Tominaga, Shogo; Miyaji, Katsuya; Yamaura, Ikuya; Yoshida, Yasuhisa; Yoshida, Kozo

2017-11-01

Chronic subdural hematoma (CSDH) is sometimes refractory, and this is troublesome for neurosurgeons. Although many studies have reported risk factors or treatments in efforts to prevent recurrence, those have focused on single recurrence, and few cumulative data are available to analyze refractory CSDH. We defined refractory CSDH as ≥2 recurrences, then analyzed and compared clinical factors between patients with single recurrence and those with refractory CSDH in a cohort study, to clarify whether patients with refractory CSDH experience different or more risk factors than patients with single recurrence, and whether burr-hole irrigation with closed-system drainage reduces refractory CSDH. Seventy-five patients had at least 1 recurrence, with single recurrence in 62 patients and ≥2 recurrences in 13 patients. In comparing clinical characteristics, patients with refractory CSDH were significantly younger (P = 0.04) and showed shorter interval to first recurrence (P < 0.001). Organized CSDH was also significantly associated with refractory CSDH (P = 0.02). Multivariate logistic regression analysis identified first recurrence interval <1 month (odds ratio, 6.66, P < 0.001) and age <71 years (odds ratio, 4.16, P < 0.001) as independent risk factors for refractory CSDH. On the other hand, burr-hole irrigation with closed-system drainage did not reduce refractory CSDH. When patients with risk factors for refractory CSDH experience recurrence, alternative surgical procedures may be considered as the second surgery, because burr-hole irrigation with closed-system drainage did not reduce refractory CSDH in our study. Copyright © 2017 Elsevier Inc. All rights reserved.

Spent refractory reuse

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

Bennett, J.P.; Kwong, K.S.; Clark, J.A.

1996-12-31

The Albany Research Center is conducting work on spent refractory recycling/alternate use, including a review of refractory usage and current recycling/disposal practices. Research has focused on the hazardous nature of some spent refractory materials, with emphasis on lead pickup. Information on the issues associated with the reuse of spent refractories will be presented, including those associated with hazardous materials.

Effects of Temperature, Oxygen Partial Pressure, and Materials Selection on Slag Infiltration into Porous Refractories for Entrained-Flow Gasifiers

NASA Astrophysics Data System (ADS)

Kaneko, Tetsuya Kenneth

The penetration rate of molten mineral contents (slag) from spent carbonaceous feedstock into porous ceramic-oxide refractory linings is a critical parameter in determining the lifecycle of integrated gasification combined cycle energy production plants. Refractory linings that withstand longer operation without interruption are desirable because they can mitigate consumable and maintenance costs. Although refractory degradation has been extensively studied for many other high-temperature industrial processes, this work focuses on the mechanisms that are unique to entrained-flow gasification systems. The use of unique feedstock mixtures, temperatures from 1450 °C to 1600 °C, and oxygen partial pressures from 10-7 atm to 10-9 atm pose engineering challenges in designing an optimal refractory material. Experimentation, characterization, and modeling show that gasifier slag infiltration into porous refractory is determined by interactions between the slag and the refractory that either form a physical barrier that impedes fluid flow or induce an increased fluid viscosity that decelerates the velocity of the fluid body. The viscosity of the slag is modified by the thermal profile of the refractory along the penetration direction as well as reactions between the slag and refractory that alter the chemistry, and thereby the thermo-physical properties of the fluid. Infiltration experiments reveal that the temperature gradient inherently present along the refractory lining limits penetration. A refractory in near-isothermal conditions demonstrates deeper slag penetration as compared to one that experiences a steeper thermal profile. The decrease in the local temperatures of the slag as it travels deeper into the refractory increases the viscosity of the fluid, which in turn slows the infiltration velocity of fluid body into the pores of the refractory microstructure. With feedstock mixtures that exhibit high iron-oxide concentrations, a transition-metal-oxide, the oxygen partial pressure of the operating atmosphere regulates the penetration of slag into refractory. The viscosity of the slag, which dictates its penetration rate, is influenced by the oxidation state of the Fe cation. Slag penetrations are shallower in oxidizing conditions than they are in reducing conditions because the iron-oxide from the slag solutions into the corundum-structured refractory and the slag is depleted of iron-oxide, increasing the viscosity of slags. Equally, the chemistries of both the refractory and slag materials dictate the course of penetration. Cr2O3-Al2O3 refractory limits mixed feedstock slag penetration through formation of a chromium spinel layer that functions as a physical obstacle against fluid flow. Al2O 3-SiO2 refractory limits eastern coal feedstock slag penetration as a result of refractory dissolution of SiO2, which increases the viscosity of slags. A physical model, which considers unidirectional fluid flow of slag through each pore of the porous microstructure of the refractory, sufficiently approximates the penetration depth of the slag into the refractory. Agreement between experiments and the physical model demonstrates that the slag is driven into the refractory by capillary pressure. Since the viscosity of the slag continuously changes as the slag travels through the inherent temperature gradient of the refractory lining, the model incorporates dynamic viscosities that are dependent on both temperature and composition to project depths that are unique to the experimental parameters. The significantly different length scales of the radial and penetration directions of the pores allows for the application of a lubrication approximation onto the momentum equation. This process produces an analytical solution that effectively envelopes the variable viscosity into a single term.

The electrochemical reduction processes of solid compounds in high temperature molten salts.

PubMed

Xiao, Wei; Wang, Dihua

2014-05-21

Solid electrode processes fall in the central focus of electrochemistry due to their broad-based applications in electrochemical energy storage/conversion devices, sensors and electrochemical preparation. The electrolytic production of metals, alloys, semiconductors and oxides via the electrochemical reduction of solid compounds (especially solid oxides) in high temperature molten salts has been well demonstrated to be an effective and environmentally friendly process for refractory metal extraction, functional materials preparation as well as spent fuel reprocessing. The (electro)chemical reduction of solid compounds under cathodic polarizations generally accompanies a variety of changes at the cathode/melt electrochemical interface which result in diverse electrolytic products with different compositions, morphologies and microstructures. This report summarizes various (electro)chemical reactions taking place at the compound cathode/melt interface during the electrochemical reduction of solid compounds in molten salts, which mainly include: (1) the direct electro-deoxidation of solid oxides; (2) the deposition of the active metal together with the electrochemical reduction of solid oxides; (3) the electro-inclusion of cations from molten salts; (4) the dissolution-electrodeposition process, and (5) the electron hopping process and carbon deposition with the utilization of carbon-based anodes. The implications of the forenamed cathodic reactions on the energy efficiency, chemical compositions and microstructures of the electrolytic products are also discussed. We hope that a comprehensive understanding of the cathodic processes during the electrochemical reduction of solid compounds in molten salts could form a basis for developing a clean, energy efficient and affordable production process for advanced/engineering materials.

Compounded Levofloxacin Triple Therapy is Safe and Effective for Refractory Helicobacter pylori.

PubMed

Mah, Xian-Jun; Gupta, Vikas; Loch, Srey Neth; Ahlenstiel, Golo; Poorten, David van de

2017-01-01

Failure of first line and subsequent Helicobacter pylori therapy is a significant problem, as alternate treatments are cumbersome and difficult to access. The purpose of this study was to evaluate the efficacy and safety of a compounded levofloxacin triple therapy in clinical practice as a second or third-line salvage regimen for Helicobacter pylori. Patients referred after first or subsequent treatment failures were prescribed compounded levofloxacin 500 mg, amoxicillin 1 g, and esomeprazole 40 mg, all twice daily for 10 days. Eradication success was determined by 14C-urea breath test or histology at least 4 weeks after completion of therapy. The study included 93 patients, the majority of whom were female (57%) with a mean age of 44. The most common indication for treatment was dyspepsia/risk reduction (84%). Median number of previous treatments was 1 (range: 1 through 6) with treatment used as second line in 83%. Helicobacter pylori eradication was achieved in 89.2% (74/83) per protocol and 79.6% (74/93) on an intention-to-treat basis. Outcome was independent of gender, ethnicity, treatment indication, or number. Treatment was well tolerated, with minor adverse events in 8.4% and only one patient discontinuing therapy. Compounded levofloxacin triple therapy is an effective and safe second line treatment for Helicobacter pylori, with eradication rates comparable to standard levofloxacin-based regimens. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Ginsenoside-Rb1 targets chemotherapy-resistant ovarian cancer stem cells via simultaneous inhibition of Wnt/β-catenin signaling and epithelial-to-mesenchymal transition

PubMed Central

Deng, Shan; Wong, Chris Kong Chu; Lai, Hung-Cheng; Wong, Alice Sze Tsai

2017-01-01

Chemoresistance is a major clinical problem compromising the successful treatment of cancer. One exciting approach is the eradication of cancer stem/tumor-initiating cells (jointly CSCs), which account for tumor initiation, progression, and drug resistance. Here we show for the first time, with mechanism-based evidence, that ginsenoside-Rb1, a natural saponin isolated from the rhizome of Panax quinquefolius and notoginseng, exhibits potent cytotoxicity on CSCs. Rb1 and its metabolite compound K could effectively suppress CSC self-renewal without regrowth. Rb1 and compound K treatment also sensitized the CSCs to clinically relevant doses of cisplatin and paclitaxel. These effects were associated with the Wnt/β-catenin signaling pathway by downregulating β-catenin/T-cell factor-dependent transcription and expression of its target genes ATP-binding cassette G2 and P-glycoprotein. We also identified reversal of epithelial-to-mesenchymal transition as a new player in the Rb1 and compound K-mediated inhibition of CSCs. Rb1 and compound K treatment also inhibited the self-renewal of CSCs derived from ovarian carcinoma patients as well as in xenograft tumor model. Moreover, we did not observe toxicity in response to doses of Rb1 and compound K that produced an anti-CSC effect. Therefore, Rb1 should be explored further as a promising nutraceutical prototype of treating refractory tumors. PMID:27825116

Reduced Intensity Chemotherapy and Radiation Therapy Before Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

ClinicalTrials.gov

2018-05-10

Acute Myeloid Leukemia; Acute Myeloid Leukemia in Remission; Aplastic Anemia; Chronic Myelomonocytic Leukemia; Hodgkin Lymphoma; Indolent Non-Hodgkin Lymphoma; Malignant Neoplasm; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Plasma Cell Myeloma; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

OnabotulinumtoxinA vs Sacral Neuromodulation on Refractory Urgency Urinary Incontinence in Women: A Randomized Clinical Trial.

PubMed

Amundsen, Cindy L; Richter, Holly E; Menefee, Shawn A; Komesu, Yuko M; Arya, Lily A; Gregory, W Thomas; Myers, Deborah L; Zyczynski, Halina M; Vasavada, Sandip; Nolen, Tracy L; Wallace, Dennis; Meikle, Susan F

2016-10-04

Women with refractory urgency urinary incontinence are treated with sacral neuromodulation and onabotulinumtoxinA with limited comparative information. To assess whether onabotulinumtoxinA is superior to sacral neuromodulation in controlling refractory episodes of urgency urinary incontinence. Multicenter open-label randomized trial (February 2012-January 2015) at 9 US medical centers involving 381 women with refractory urgency urinary incontinence. Cystoscopic intradetrusor injection of 200 U of onabotulinumtoxinA (n = 192) or sacral neuromodulation (n = 189). Primary outcome, change from baseline mean number of daily urgency urinary incontinence episodes over 6 months, was measured with monthly 3-day diaries. Secondary outcomes included change from baseline in urinary symptom scores in the Overactive Bladder Questionnaire Short Form (SF); range, 0-100, higher scores indicating worse symptoms; Overactive Bladder Satisfaction questionnaire; range, 0-100; includes 5 subscales, higher scores indicating better satisfaction; and adverse events. Of the 364 women (mean [SD] age, 63.0 [11.6] years) in the intention-to-treat population, 190 women in the onabotulinumtoxinA group had a greater reduction in 6-month mean number of episodes of urgency incontinence per day than did the 174 in the sacral neuromodulation group (-3.9 vs -3.3 episodes per day; mean difference, 0.63; 95% CI, 0.13 to 1.14; P = .01). Participants treated with onabotulinumtoxinA showed greater improvement in the Overactive Bladder Questionnaire SF for symptom bother (-46.7 vs -38.6; mean difference, 8.1; 95% CI, 3.0 to 13.3; P = .002); treatment satisfaction (67.7 vs 59.8; mean difference, 7.8; 95% CI, 1.6 to 14.1; P = .01) and treatment endorsement (78.1 vs 67.6; mean difference; 10.4, 95% CI, 4.3 to 16.5; P < .001) than treatment with sacral neuromodulation. There were no differences in convenience (67.6 vs 70.2; mean difference, -2.5; 95% CI, -8.1 to 3.0; P = .36), adverse effects (88.4 vs 85.1; mean difference, 3.3; 95% CI, -1.9 to 8.5; P = .22), and treatment preference (92.% vs 89%; risk difference, -3%; 95% CI, -16% to 10%; P = .49). Urinary tract infections were more frequent in the onabotulinumtoxinA group (35% vs 11%; risk difference, -23%; 95% CI, -33% to -13%; P < .001). The need for self-catheterization was 8% and 2% at 1 and 6 months in the onabotulinumtoxinA group. Neuromodulation device revisions and removals occurred in 3%. Among women with refractory urgency urinary incontinence, treatment with onabotulinumtoxinA compared with sacral neuromodulation resulted in a small daily improvement in episodes that although statistically significant is of uncertain clinical importance. In addition, it resulted in a higher risk of urinary tract infections and need for transient self-catheterizations.

Chromia refractory brick with carbon treatment

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

Bennett, James P.; Kwong, Kyei-Sing

The disclosure provides a refractory brick system comprising a chromia refractory brick for operation in the slagging environment of an air-cooled gasifier. The chromia refractory brick comprises a ceramically-bonded porous chromia refractory having a porosity greater than 9% and having carbon deposits residing within the pores. The brick may be further comprised of Al.sub.2O.sub.3. The air-cooled gasifier generates a liquefied slag in contact with the refractory brick and generally operates at temperatures between 1250.degree. C. and 1575.degree. C. and pressures between 300 psi to 1000 psi, with oxygen partial pressures generally between 10.sup.-4 and 10.sup.-10 atm. The refractory brick performsmore » without substantial chromium carbide or chromium metal formation in the low oxygen partial pressure environment. The inclusion of carbon without chromium carbide formation provides for significant mitigation of slag penetration and significantly reduced refractory wear.« less

Conventional versus robot-assisted laparoscopic Nissen fundoplication: a comparison of postoperative acid reflux parameters.

PubMed

Frazzoni, Marzio; Conigliaro, Rita; Colli, Giovanni; Melotti, Gianluigi

2012-06-01

Laparoscopic Nissen fundoplication (LNF) is a technically demanding surgical procedure designed to cure gastroesophageal reflux disease (GERD). It represents an alternative to life-long medical therapy and the only recommended treatment modality to overcome refractoriness to proton pump inhibitor (PPI) therapy. The recent development of robotic systems prompted evaluation of their use in antireflux surgery. Between 1997 and 2000, in a PPI-responsive series we found postoperative normalization of esophageal acid exposure time (EAET) in most but not all cases. Between 2007 and 2009, in a PPI-refractory series we found postoperative normalization of EAET in all cases. We decided to analyze retrospectively our prospectively collected data to evaluate whether differences other than the conventional or robot-assisted technique could justify postoperative differences in acid reflux parameters. Baseline demographic, endoscopic, and manometric parameters were compared between the two series of patients, as well as postoperative manometric and acid reflux parameters. There were no significant differences in the baseline demographic, endoscopic, and manometric characteristics between the two groups of patients. The median lower esophageal sphincter tone increased significantly, and the median EAET decreased significantly after conventional as well as after robot-assisted LNF. The median postoperative EAET was significantly lower in the robot-assisted (0.2%) than in the conventional LNF group (1%; P = 0.001). Abnormal EAET values were found in 6 of 44 (14%) and in 0 of 44 cases after conventional and robot-assisted LNF, respectively (P = 0.026). Robot-assisted LNF provided a significant gain in postoperative acid reflux parameters compared with the conventional technique. In a challenging clinical setting, such as PPI-refractoriness, in which the efficacy of endoscopic or pharmacological treatment modalities is only moderate, even a small therapeutic gain can be clinically relevant. In centers where robot-assisted LNF is available, it should be preferred to conventional LNF in PPI-refractory GERD.

Distinguishing in-hospital and out-of-hospital status epilepticus: clinical implications from a 10-year cohort study.

PubMed

Sutter, R; Semmlack, S; Spiegel, R; Tisljar, K; Rüegg, S; Marsch, S

2017-09-01

The aim was to determine differences of clinical, treatment and outcome characteristics between patients with in-hospital and out-of-hospital status epilepticus (SE). From 2005 to 2014, clinical data were assessed in adults with SE treated in an academic medical care centre. Clinical characteristics, treatment and outcomes were compared between patients with in-hospital and out-of-hospital SE. Amongst 352 patients, 213 were admitted with SE and 139 developed in-hospital SE. Patients with in-hospital SE had more acute/fatal aetiologies (60% vs. 35%, P < 0.001), fewer previous seizures (33% vs. 50%, P = 0.002), a higher median Charlson Comorbidity Index (3 vs. 2, P < 0.001), longer median SE duration (1 vs. 0.5 days, P = 0.001), more refractory SE (52% vs. 39%, P = 0.022), less return to functional baseline (38% vs. 54%, P = 0.006) and increased mortality (29% vs. 19%, P = 0.001). Whilst in multivariable analyses an increasing Status Epilepticus Severity Score (STESS) was an independent predictor for death in both groups, increased Charlson Comorbidity Index and treatment refractory SE were associated with death only in patients with in-hospital SE. Continuous anaesthesia for refractory SE was associated with increased mortality only in patients with out-of-hospital SE. The area under the receiver operating curve was 0.717 for prediction of death by STESS in patients with in-hospital SE and 0.811 in patients with out-of-hospital SE. Patients with in-hospital SE had more fatal aetiologies and comorbidities, refractory SE, less return to functional baseline, and increased mortality compared to patients with out-of-hospital SE. Whilst the STESS was a robust predictor for death in both groups, the association between continuous anaesthesia and death was limited to out-of-hospital SE. © 2017 EAN.

Interface Analyses Between a Case-Hardened Ingot Casting Steel and Carbon-Containing and Carbon-Free Refractories

NASA Astrophysics Data System (ADS)

Fruhstorfer, Jens; Dudczig, Steffen; Rudolph, Martin; Schmidt, Gert; Brachhold, Nora; Schöttler, Leandro; Rafaja, David; Aneziris, Christos G.

2018-06-01

Corrosion tests of carbon-free and carbon-containing refractories were performed. The carbon-free crucibles corroded, whereas the carbon-containing crucibles were negligibly attacked. On them, inclusions were attached. This study investigates melt oxygen contents, interface properties, and steel compositions with their non-metallic inclusions in order to explore the inclusion formation and deposition mechanisms. The carbon-free crucibles were based on alumina, mullite, and zirconia- and titania-doped alumina (AZT). The carbon-containing (-C) ones were alumina-C and AZT-C. Furthermore, nanoscaled carbon and alumina additives (-n) were applied in an AZT-C-n material. In the crucibles, the case-hardened steel 17CrNiMo7-6 was remelted at 1580 °C. It was observed that the melt and steel oxygen contents were higher for the tests in the carbon-free crucibles. Into these crucibles, the deoxidizing alloying elements Mn and Si diffused. Reducing contents of deoxidizing elements resulted in higher steel oxygen levels and less inclusions, mainly of the inclusion group SiO2-core-MnS-shell (2.5 to 8 μ m). These developed from smaller SiO2 nuclei. The inclusion amount in the steel was highest after remelting in AZT-C-n for 30 minutes but decreased strongly with increasing remelting time (60 minutes) due to inclusions' deposition on the refractory surface. The Ti from the AZT and the nanoadditives supported inclusion growth and deposition. Other inclusion groups were alumina and calcium aluminate inclusions. Their contents were high after remelting in carbon- or AZT-containing crucibles but generally decreased during remelting. On the AZT-C-n crucible, a dense layer formed from vitreous compositions including Al, Ca, Mg, Si, and Ti. To summarize, for reducing forming inclusion amounts, mullite is recommended as refractory material. For capturing formed inclusions, AZT-C-n showed a high potential.

Randomized trial of TAS-102 for refractory metastatic colorectal cancer.

PubMed

Mayer, Robert J; Van Cutsem, Eric; Falcone, Alfredo; Yoshino, Takayuki; Garcia-Carbonero, Rocio; Mizunuma, Nobuyuki; Yamazaki, Kentaro; Shimada, Yasuhiro; Tabernero, Josep; Komatsu, Yoshito; Sobrero, Alberto; Boucher, Eveline; Peeters, Marc; Tran, Ben; Lenz, Heinz-Josef; Zaniboni, Alberto; Hochster, Howard; Cleary, James M; Prenen, Hans; Benedetti, Fabio; Mizuguchi, Hirokazu; Makris, Lukas; Ito, Masanobu; Ohtsu, Atsushi

2015-05-14

Early clinical trials conducted primarily in Japan have shown that TAS-102, an oral agent that combines trifluridine and tipiracil hydrochloride, was effective in the treatment of refractory colorectal cancer. We conducted a phase 3 trial to further assess the efficacy and safety of TAS-102 in a global population of such patients. In this double-blind study, we randomly assigned 800 patients, in a 2:1 ratio, to receive TAS-102 or placebo. The primary end point was overall survival. The median overall survival improved from 5.3 months with placebo to 7.1 months with TAS-102, and the hazard ratio for death in the TAS-102 group versus the placebo group was 0.68 (95% confidence interval [CI], 0.58 to 0.81; P<0.001). The most frequently observed clinically significant adverse events associated with TAS-102 were neutropenia, which occurred in 38% of those treated, and leukopenia, which occurred in 21%; 4% of the patients who received TAS-102 had febrile neutropenia, and one death related to TAS-102 was reported. The median time to worsening performance status (a change in Eastern Cooperative Oncology Group performance status [on a scale of 0 to 5, with 0 indicating no symptoms and higher numbers indicating increasing degrees of disability] from 0 or 1 to 2 or more) was 5.7 months with TAS-102 versus 4.0 months with placebo (hazard ratio, 0.66; 95% CI, 0.56 to 0.78; P<0.001). In patients with refractory colorectal cancer, TAS-102, as compared with placebo, was associated with a significant improvement in overall survival. (Funded by Taiho Oncology-Taiho Pharmaceutical; RECOURSE ClinicalTrials.gov number, NCT01607957.).

An Open-Label, Analgesic Efficacy and Safety of Pituitary Radiosurgery for Patients With Opioid-Refractory Pain: Study Protocol for a Randomized Controlled Trial.

PubMed

Borius, Pierre-Yves; Garnier, Stéphanie Ranque; Baumstarck, Karine; Castinetti, Frédéric; Donnet, Anne; Guedj, Eric; Cornu, Philippe; Blond, Serge; Salas, Sébastien; Régis, Jean

2017-08-02

Hypophysectomy performed by craniotomy or percutaneous techniques leads to complete pain relief in more than 70% to 80% of cases for opioid refractory cancer pain. Radiosurgery could be an interesting alternative approach to reduce complications. To assess the analgesic efficacy compared with standard of care is the primary goal. The secondary objectives are to assess ophthalmic and endocrine tolerance, drug consumption, quality of life, and mechanisms of analgesic action. The trial is multicenter, randomized, prospective, and open-label with 2 parallel groups. This concerns patients in palliative care suffering from nociceptive or mixed cancer pain, refractory to standard opioid therapy. Participants will be randomly assigned to the control group receiving standards of care for pain according to recommendations, or to the experimental group receiving a pituitary GammaKnife (Elekta, Stockholm, Sweden) radiosurgery (160 Gy delivered in pituitary gland) associated with standards of care. Evaluation assessments will be taken at baseline, day0, day4, day7, day14, day28, day45, month3, and month6. We could expect pain improvement in 70% to 90% of cases at day4. In addition we will assess the safety of pituitary radiosurgery in a vulnerable population. The secondary endpoints could show decay of opioid consumption, good patient satisfaction, and improvement of the quality of life. The design of this study is potentially the most appropriate to demonstrate the efficacy and safety of radiosurgery for this new indication. New recommendations could be obtained in order to improve pain relief and quality of life. Copyright © 2017 by the Congress of Neurological Surgeons

269 Refractory Chronic Urticaria Treated with Omalizumab

PubMed Central

Saenz, Martinez; Del Pozo, Ramírez; JJ, Lopez Tiro; Vera, Javier Gomez

2012-01-01

Background Chronic urticaria (CU) is a common disorder characterized by recurrent episodes of urticaria pruritic erythematous lesions, associated with angioedema1. It affects 0.1% of the population, it is estimated that approximately 15 to 25% of the population will have hives at some point in their lives.2 About 80% of UC patients are diagnosed as idiopathic chronic urticaria and that no cause is identified, 3 experiencing deterioration in their quality of life affecting your work, social relationships, schemes requiring multiple medications and doses higher than usual. This study proposes Omalizumab (anti-IgE humanized antibody) as a treatment for Refractory Chronic Urticaria (RCU) Object Demonstrate Omalizumab's effectiveness in the treatment of Refractory Chronic Urticaria. Methods A clinical study, was carried out to evaluate the effectiveness of the Omalizumab's treatment on RCU diagnosed patient, including male and female patients ages 12 to 50 diagnosed with RCU, with Scorad higher tan 30 points. We made a questionnaire to know about the patient's family background, skin symptoms beginning, administration of drugs such sistemic steroids, inmunosupresors, calceurine inhibitors, presence of inmunotherapy and age of start. Omalizumab was administered on doses according patient's weight and IgE levels, bimonthly or monthly according to treatment guides. Severeness level was calculated with scorad every 1 month, with IgE seric level measurement and life quality questionnaire. Results 5 patients diagnosed with RCU were included in the group of Omalizumab and 5 patients in the control group (placebo). All patients were female. A gradual decrease on the life quality score and in Score, with a significant P under 0.05 was observed on all patients treated with omalizumab compared with patient in the group with placebo. Conclusions Treatment with Omalizumab progressively decreases the severeness level on RCU, with a significant improvement on the patient's life quality.

Efficient Destruction of Pollutants in Water by a Dual-Reaction-Center Fenton-like Process over Carbon Nitride Compounds-Complexed Cu(II)-CuAlO2.

PubMed

Lyu, Lai; Yan, Dengbiao; Yu, Guangfei; Cao, Wenrui; Hu, Chun

2018-04-03

Carbon nitride compounds (CN) complexed with the in-situ-produced Cu(II) on the surface of CuAlO 2 substrate (CN-Cu(II)-CuAlO 2 ) is prepared via a surface growth process for the first time and exhibits exceptionally high activity and efficiency for the degradation of the refractory pollutants in water through a Fenton-like process in a wide pH range. The reaction rate for bisphenol A removal is ∼25 times higher than that of the CuAlO 2 . According to the characterization, Cu(II) generation on the surface of CuAlO 2 during the surface growth process results in the marked decrease of the surface oxygen vacancies and the formation of the C-O-Cu bridges between CN and Cu(II)-CuAlO 2 in the catalyst. The electron paramagnetic resonance (EPR) analysis and density functional theory (DFT) calculations demonstrate that the dual reaction centers are produced around the Cu and C sites due to the cation-π interactions through the C-O-Cu bridges in CN-Cu(II)-CuAlO 2 . During the Fenton-like reactions, the electron-rich center around Cu is responsible for the efficient reduction of H 2 O 2 to • OH, and the electron-poor center around C captures electrons from H 2 O 2 or pollutants and diverts them to the electron-rich area via the C-O-Cu bridge. Thus, the catalyst exhibits excellent catalytic performance for the refractory pollutant degradation. This study can deepen our understanding on the enhanced Fenton reactivity for water purification through functionalizing with organic solid-phase ligands on the catalyst surface.

Heterogeneous Oxidation of Laboratory-generated Mixed Composition and Biomass Burning Particles

NASA Astrophysics Data System (ADS)

Lim, C. Y.; Sugrue, R. A.; Hagan, D. H.; Cappa, C. D.; Kroll, J. H.; Browne, E. C.

2016-12-01

Heterogeneous oxidation of organic aerosol (OA) can significantly transform the chemical and physical properties of particulate matter in the atmosphere, leading to changes to the chemical composition of OA and potential volatilization of organic compounds. It has become increasingly apparent that the heterogeneous oxidation kinetics of OA depend on the phase and morphology of the particles. However, most laboratory experiments to date have been performed on single-component, purely organic precursors, which may exhibit fundamentally different behavior than more complex particles in the atmosphere. Here we present laboratory studies of the heterogeneous oxidation of two more complex chemical systems: thin, organic coatings on inorganic seed particles and biomass burning OA. In the first system, squalane (C30H62), a model compound for reduced OA, is coated onto dry ammonium sulfate particles at various thicknesses (10-20 nm) and exposed to hydroxyl radical (OH) in a flow tube reactor. In the second, we use a semi-batch reactor to study the heterogeneous OH-initiated oxidation of biomass burning particles as a part of the 2016 FIREX campaign in Missoula, MT. The resulting changes in chemical composition are monitored with an Aerodyne High Resolution Time-of-flight Aerosol Mass Spectrometer (AMS) and a soot-particle AMS for the non-refractory and refractory systems, respectively. We show that the heterogeneous oxidation kinetics of these multicomponent particles are substantially different than that of the single-component particles. The oxidation of organic coatings is rapid, undergoing dramatic changes to carbon oxidation state and losing a significant amount of organic mass after relatively low OH exposures (equivalent to several days of atmospheric processing). In the case of biomass burning particles, the kinetics are complex, with different components (inferred by aerosol mass spectrometry) undergoing oxidation at different rates.

Molecular-level characterization of reactive and refractory dissolved natural organic nitrogen compounds by atmospheric pressure photoionization coupled to Fourier transform ion cyclotron resonance mass spectrometry.

PubMed

Osborne, Daniel M; Podgorski, David C; Bronk, Deborah A; Roberts, Quinn; Sipler, Rachel E; Austin, David; Bays, James S; Cooper, William T

2013-04-30

Dissolved organic nitrogen (DON) represents a significant fraction of the total dissolved nitrogen pool in most surface waters and serves as an important nitrogen source for phytoplankton and bacteria. As with other natural organic matter mixtures, ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS) is the only technique currently able to provide molecular composition information on DON. Although electrospray ionization (ESI) is the most commonly used ionization method, it is not very efficient at ionizing most DON components. Positive- and negative-mode atmospheric pressure photoionization (APPI) coupled with ultrahigh resolution FTICRMS at 9.4 T were compared for determining the composition of DON before and after bioassays. Toluene was added as the APPI dopant to the solid-phase DON extracts, producing a final sample that was 90% methanol and 10% toluene by volume. Positive-mode (+) APPI proved significantly more efficient at ionizing DON; 62% of the formulas that could be assigned in the positive-ion spectrum contained at least one nitrogen atom vs. 31% in the negative-ion spectrum. FTICR mass spectral data indicated that most of the refractory DON compounds (i.e. nonreactive during the 5 days of the incubation) had molecular compositions representative of lignin-like molecules, while lipid-like and protein-like molecules comprised most of the small reactive component of the DON pool. From these data we conclude that (+) APPI FTICRMS is a promising technique for describing the molecular composition of DON mixtures. The technique is particularly valuable in assessing the bioavailability of individual components of DON when combined with bioassays. Copyright © 2013 John Wiley & Sons, Ltd.

Catalytic ozonation of petroleum refinery wastewater utilizing Mn-Fe-Cu/Al2O 3 catalyst.

PubMed

Chen, Chunmao; Yoza, Brandon A; Wang, Yandan; Wang, Ping; Li, Qing X; Guo, Shaohui; Yan, Guangxu

2015-04-01

There is of great interest to develop an economic and high-efficient catalytic ozonation system (COS) for the treatment of biologically refractory wastewaters. Applications of COS require options of commercially feasible catalysts. Experiments in the present study were designed to prepare and investigate a novel manganese-iron-copper oxide-supported alumina-assisted COS (Mn-Fe-Cu/Al2O3-COS) for the pretreatment of petroleum refinery wastewater. The highly dispersed composite metal oxides on the catalyst surface greatly promoted the performance of catalytic ozonation. Hydroxyl radical mediated oxidation is a dominant reaction in Mn-Fe-Cu/Al2O3-COS. Mn-Fe-Cu/Al2O3-COS enhanced COD removal by 32.7% compared with a single ozonation system and by 8-16% compared with Mn-Fe/Al2O3-COS, Mn-Cu/Al2O3-COS, and Fe-Cu/Al2O3-COS. The O/C and H/C ratios of oxygen-containing polar compounds significantly increased after catalytic ozonation, and the biodegradability of petroleum refinery wastewater was significantly improved. This study illustrates potential applications of Mn-Fe-Cu/Al2O3-COS for pretreatment of biologically refractory wastewaters.

Ulcerative proctitis: an update on the pharmacotherapy and management.

PubMed

Gecse, Krisztina B; Lakatos, Peter L

2014-08-01

Ulcerative colitis (UC) presents as proctitis in approximately a quarter of the patients. It may progress into left-sided or extensive colitis in up to 50% of cases upon long-term follow-up. Currently available data on ulcerative proctitis are summarized and critically reviewed. Extensive literature search (MEDLINE) was performed to identify relevant articles up to March 2014. The short-term goal of the treatment in UC is to induce remission, whereas long-term goals are to maintain remission and prevent disease progression. Topically administered 5-aminosalicylates (5-ASA) and corticosteroids are effective in the treatment of proctitis, although they seem to be underused in everyday practice. Locally administered 5-ASA preparations are more effective than oral compounds. The combination of topical and oral 5-ASA and steroids should be considered for escalation of treatment. Refractory patients should be re-evaluated to exclude for compliance failures, infections or proximal disease extent. True refractory or steroid-dependent patients may require immunomodulators or biological therapy. Alternative medicine can be used complementarily, while experimental approaches are reserved for patients failing conventional medication. Proctocolectomy may be the last resort of treatment. Upon long-term, 5-ASA maintenance treatment is indicated in all UC cases to prevent relapse and disease progression.

Characterization studies of prototype ISOL targets for the RIA

NASA Astrophysics Data System (ADS)

Greene, John P.; Burtseva, Tatiana; Neubauer, Janelle; Nolen, Jerry A.; Villari, Antonio C. C.; Gomes, Itacil C.

2005-12-01

Targets employing refractory compounds are being developed for the rare isotope accelerator (RIA) facility to produce ion species far from stability. With the 100 kW beams proposed for the production targets, dissipation of heat becomes a challenging issue. In our two-step target design, neutrons are generated in a refractory primary target, inducing fission in the surrounding uranium carbide. The interplay of density, grain size, thermal conductivity and diffusion properties of the UC2 needs to be well understood before fabrication. Thin samples of uranium carbide were prepared for thermal conductivity measurements using an electron beam to heat the sample and an optical pyrometer to observe the thermal radiation. Release efficiencies and independent thermal analysis on these samples are being undertaken at Oak Ridge National Laboratory (ORNL). An alternate target concept for RIA, the tilted slab approach promises to be simple with fast ion release and capable of withstanding high beam intensities while providing considerable yields via spallation. A proposed small business innovative research (SBIR) project will design a prototype tilted target, exploring the materials needed for fabrication and testing at an irradiation facility to address issues of heat transfer and stresses within the target.

Pediatric status epilepticus: improved management with new drug therapies?

PubMed

Verrotti, Alberto; Ambrosi, Michela; Pavone, Piero; Striano, Pasquale

2017-06-01

Status Epilepticus (SE) is the most common neurological emergency of childhood. It requires prompt administration of appropriately selected anti-seizure medications. Areas covered: Following a distinction between estabilished and emergent drugs, we present pharmacological treatment options and their clinical utility in children, with a short mention on alternatives to drug treatment. We also propose an algorithm for the management of pediatric SE. For this review a Pubmed, Medline and Embase search was performed. Expert opinion: In early SE in children, in the prehospital setting, rectal diazepam or buccal midazolam are efficacious drugs; whereas in the hospital setting, intravenous lorazepam or diazepam are indicated. As regard estabilished stage of SE, in addition to the 'classic' compounds, such as phenytoin and phenobarbital, other drugs such as valproic acid, levetiracetam and lacosamide have been demonstrated efficacious. Treatment recommendations of refractory SE depend on retrospective case series and uncontrolled studies. We reported experiences about the use of midazolam, propofol, ketamine and lidocaine. They could be a valid option, but further prospective studies are necessary. Over the last few decades, important advances in basic mechanisms underlying refractory SE have been achieved, but few data are available regarding management of these stages.

[Special penetration needling for refractory peripheral facial paralysis].

PubMed

Cao, Rongjuan; Qiu, Xiaohu; Xie, Xiaokun

2018-03-12

To observe the clinical effect difference between special penetration needling and conventional penetration needling for the refractory peripheral facial paralysis. A total of 97 patients with intractable facial paralysis were randomized into an observation group (49 cases and 2 dropping) and a control group (48 cases and 4 dropping). In the observation group, special penetration needling at an angle about 45° between the penetration needle and paralysis muscle bundle was used, Yangbai (GB 14) through Touwei (ST 8), Yangbai (GB 14) through Shangxing (GV 23), Sizhukong (TE 23) through Yuyao (EX-HN 4), Qianzhen (Extra) through Yingxiang (LI 20), mutual penetration between Yingxiang (LI 20) and Jiache (ST 6). Conventional penetration needling was applied in the control group, Yangbai (GB 14) through Yuyao (EX-HN 4), Cuanzhu (BL 2) through Yuyao (EX-HN 4), mutual penetration between Dicang (ST 4) and Jiache (ST 6), Qianzheng (Extra) through Dicang (ST 4), Sibai (ST 2) through Yingxiang (LI 20). Three groups of electroacupuncture (discontinuous wave, 1 Hz) with tolerance were connected respectively in the two groups, Yangbai (GB 14) and Sizhukong (TE 23), Yangbai (GB 14) and Qianzheng (Extra), Yingxiang (LI 20) and Jiache (ST 6) in the observation group, Yangbai (GB 14) and Cuanzhu (BL 2), Dicang (ST 4) and Jiache (ST 6), Qianzheng (Extra) and Sibai (ST 2) in the control group. TDP was applied in the two groups at the affected Yifeng (TE 17), Jiache (ST 6) and Qianzheng (Extra), which were around the ear. Perpendicular insertion was used at Yifeng (TE 17) at the affected side and Hegu (LI 4) at the healthy side and bilateral Zusanli (ST 36). The needles were retained for 30 min. The treatment was given for 3 courses, once a day and 10 days as a course, 5 days at the interval. House-Brackmann (H-B) facial nerve grading score was recorded before and after treatment. The clinical effects were compared. The H-B scores after treatment in the two groups were higher than those before treatment (both P <0.05), with better result in the observation group ( P <0.05). The cured and markedly effective rate of the observation group was 74.5% (35/47), which was better than 47.7% (21/44) of the control group ( P <0.01). Special penetration needling at an angle about 45° between the penetration needle and paralysis muscle bundle is better than conventional penetration needling for refractory facial paralysis.

Chromium oxidation state mapping in human cells

NASA Astrophysics Data System (ADS)

Ortega, R.; Fayard, B.; Salomé, M.; Devès, G.; Susini, J.

2003-03-01

The widespread use of chromium in industrial applications such as chemical production of pigments, refractory brick production, tanning, metallurgy, electroplating, and combustion of fuels has lead to human occupational exposure and to its increased introduction into the environment. Hexavalent chromium compounds are established carcinogens but their mechanism of cell transformation is not known. Up to now, no microanalytical technique was sensitive enough to allow the observation of chromium distribution, and oxidation state identification, within isolated cells at carcinogenic concentrations. In this experiment, we used successfully the ID-21 X-ray microscope to map Cr(VI) and total Cr distributions in cells exposed in vitro to soluble, and insoluble, Cr(VI) compounds. Exposure to soluble compounds, weak carcinogens, resulted in a homogeneous intracellular distribution of Cr, confirming by in situ measurement that Cr is present in the cell nucleus. Cr(VI) was never detected in cells which suggests a mechanism of rapid intracellular reducticn. On the other hand, exposure to insoluble compounds, strong carcinogens, also resulted in a homogeneous distribution of reduced forms of Cr in cells, and their nucleus. However, in this case, Cr(VI)-rich structures were observed into the cells suggesting that carcinogenicity is enhanced when oxidation reactions due to Cr(VI) chronic exposure are associated to Cr-DNA alterations.

Organics and nitrogen removal from textile auxiliaries wastewater with A2O-MBR in a pilot-scale.

PubMed

Sun, Faqian; Sun, Bin; Hu, Jian; He, Yangyang; Wu, Weixiang

2015-04-09

The removal of organic compounds and nitrogen in an anaerobic-anoxic-aerobic membrane bioreactor process (A(2)O-MBR) for treatment of textile auxiliaries (TA) wastewater was investigated. The results show that the average effluent concentrations of chemical oxygen demand (COD), ammonium nitrogen (NH4(+)-N) and total nitrogen (TN) were about 119, 3 and 48 mg/L under an internal recycle ratio of 1.5. The average removal efficiency of COD, NH4(+)-N and TN were 87%, 96% and 55%, respectively. Gas chromatograph-mass spectrometer analysis indicated that, although as much as 121 different types of organic compounds were present in the TA wastewater, only 20 kinds of refractory organic compounds were found in the MBR effluent, which could be used as indicators of effluents from this kind of industrial wastewater. Scanning electron microscopy analysis revealed that bacterial foulants were significant contributors to membrane fouling. An examination of foulants components by wavelength dispersive X-ray fluorescence showed that the combination of organic foulants and inorganic compounds enhanced the formation of gel layer and thus caused membrane fouling. The results will provide valuable information for optimizing the design and operation of wastewater treatment system in the textile industry. Copyright © 2015 Elsevier B.V. All rights reserved.

Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

ClinicalTrials.gov

2018-06-25

Adenoid Cystic Carcinoma; Adnexal Carcinoma; Apocrine Carcinoma; Eccrine Porocarcinoma; Extraocular Cutaneous Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Non-Melanomatous Lesion; Paget Disease; Papillary Adenocarcinoma; Primary Cutaneous Mucinous Carcinoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Spiradenocarcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage III Skin Cancer; Stage IV Skin Cancer; Sweat Gland Carcinoma; Trichilemmocarcinoma; Vulvar Squamous Cell Carcinoma

Evidence for Extended Aqueous Alteration in CR Carbonaceous Chondrites

NASA Technical Reports Server (NTRS)

Trigo-Rodriquez, J. M.; Moyano-Cambero, C. E.; Mestres, N.; Fraxedas, J.; Zolensky, M.; Nakamura, T.; Martins, Z.

2013-01-01

We are currently studying the chemical interrelationships between the main rockforming components of carbonaceous chondrites (hereafter CC), e.g. silicate chondrules, refractory inclusions and metal grains, and the surrounding meteorite matrices. It is thought that the fine-grained materials that form CC matrices are representing samples of relatively unprocessed protoplanetary disk materials [1-3]. In fact, modern non-destructive analytical techniques have shown that CC matrices host a large diversity of stellar grains from many distinguishable stellar sources [4]. Aqueous alteration has played a role in homogeneizing the isotopic content that allows the identification of presolar grains [5]. On the other hand, detailed analytical techniques have found that the aqueously-altered CR, CM and CI chondrite groups contain matrices in which the organic matter has experienced significant processing concomitant to the formation of clays and other minerals. In this sense, clays have been found to be directly associated with complex organics [6, 7]. CR chondrites are particularly relevant in this context as this chondrite group contains abundant metal grains in the interstitial matrix, and inside glassy silicate chondrules. It is important because CR are known for exhibiting a large complexity of organic compounds [8-10], and only metallic Fe is considered essential in Fischer-Tropsch catalysis of organics [11-13]. Therefore, CR chondrites can be considered primitive materials capable to provide clues on the role played by aqueous alteration in the chemical evolution of their parent asteroids.

Pregabalin as mono- or add-on therapy for patients with refractory chronic neuropathic pain: a post-marketing prescription-event monitoring study.

PubMed

Lampl, Christian; Schweiger, Christine; Haider, Bernhard; Lechner, Anita

2010-08-01

This observational study examined the outcome of two different therapeutic strategies in the treatment of chronic neuropathic pain by including pregabalin (PGB) as mono- or add-on therapy in one of two treatment options. Patients with a pain score of > or =4, refractory to usual care for neuropathic pain for at least 6 months, were allocated consecutively to one of two treatment strategies according to the decision of the physician: complete switch to a flexible-dosage, monotherapeutic or add-on therapy with pregabalin (PGB group), or change established doses and combinations of pre-existing mono- or combination therapy without pregabalin (non-PGB group). After 4 weeks (primary endpoint) a significant improvement in pain reduction was documented in both intention-to treat (ITT) analysis (PGB group, n = 85: mean pain score reduction of 3.53, SD 2.03, p < 0.001; non-PGB group, n = 102; mean pain score reduction of 2.83, SD 2.23, p < 0.001) and per-protocol (PP) analysis (PGB group, n = 79: mean pain score reduction 3.53 vs. 2.83, p < 0.05; non-PGB group, n = 81; 3.5 vs. 2.9, p < 0.05) compared to baseline. Comparison of the results observed in the two groups shows that patients in the PGB group achieved significantly greater pain reduction. These results demonstrate that PGB administered twice daily is superior to treatment regimes without PGB in reducing pain and pain-related interference in quality of life.

Practical aspects of the use of phosphate binding materials in refractory mixtures, mortars and putties

NASA Technical Reports Server (NTRS)

Soltysik, B.; Pawelek, A.; Witkowska, E.

1983-01-01

Phosphate binders, particularly acidic phosphates of Al and Cr, are used for binding Al silicate refractories used for lining of burners, SiC refractories, and refractory mortars. The binders have apparent d. 2.13-2.18 g/cu cm, porosity 21.4-23.8%, compressive strength 223 71 kg/ sq cm, total shrinkage 0.2-0.8%, and refractoriness 1240 deg.

Laboratory Investigations of the Complex Refractory Organic Material Produced from Irradiation of Pluto Ice Analogs

NASA Technical Reports Server (NTRS)

Materese, Christopher K.; Cruikshank, Dale P.; Sanford, Scott A.; Imanaka, Hiroshi

2014-01-01

Much of Pluto's surface consists of N2 ice with smaller amounts of CH4 and CO ices. Despite the low temperature (approximately 45K), chemistry can be driven in the surface ices by radiation processing such as cosmic ray bombardment. When cosmic rays strike the surface, much of their energy is dispersed in the form of secondary electrons, which in turn drive much of the resulting chemical reactions. Laboratory experiments designed to simulate the conditions on these icy bodies may provide insight into this chemistry. Significant progress has been made in the laboratory toward understanding the smaller, simple compounds produced in the solid phase by radiation processing of (N2, CH4, CO) ices (Bohn et al. 1994; Moore & Hudson 2003; Hodyss et al. 2011; Kim and Kaiser 2012). Recently Materese et al. (2014) used a variety of techniques to better characterize the refractory materials produced from the UV photo-irradiation of N2:CH4:CO ices. However, because Pluto's atmosphere is optically thick to Lyman-alpha UV radiation it is important to re-examine the results using an alternate radiation source. Our latest work has consisted of the analysis of refractory materials produced from the electron bombardment of low temperature N2(-), CH4(-), and CO(-)containing ices (100:1:1). The ice mixture was chosen to be analogous to the known surface ices on Pluto and the radiation source was chosen to mimic the secondary electrons produced by cosmic rays bombardment. The residues were studied using multiple chemical techniques including, infrared (IR) spectroscopy, X-ray absorption near-edge structure (XANES) spectroscopy, and gas chromatography coupled with mass spectrometry (GC-MS). The organic residues produced in these experiments can be seen as an analog for the refractory component of the surface of Pluto, and are compared with the residues previously obtained from UV photo-irradiation. UV and near- IR spectroscopy of the surfaces of Pluto and Charon during the encounter with NASA's New Horizons spacecraft in 2015, will give the first close-up measurements of ices and their photoproducts. Laboratory measurements and experiments will provide a better context for the data returned by the spacecraft.

In vivo detection of clinically non-apparent ocular surface inflammation in patients with meibomian gland dysfunction-associated refractory dry eye symptoms: a pilot study

PubMed Central

Qazi, Y; Kheirkhah, A; Blackie, C; Cruzat, A; Trinidad, M; Williams, C; Korb, D R; Hamrah, P

2015-01-01

Purpose The utility of in vivo confocal microscopy (IVCM) in the investigation of palpebral conjunctival and corneal inflammation in patients with meibomian gland dysfunction (MGD)-associated refractory dry eye symptoms following gland expression, despite objective clinical improvement. Methods A retrospective, observational pilot study was conducted evaluating five patients with MGD-associated refractory dry eye symptoms and three control groups: symptomatic untreated MGD patients (n=3), treatment-responsive MGD patients with improved symptoms (n=3) and asymptomatic healthy normals (n=11). Ocular surface disease index (OSDI) scores, tear break-up time (TBUT), the number of meibomian glands yielding liquid secretion (MGYLS), palpebral conjunctival epithelial and substantia propria immune cell (EIC, SIC), and corneal dendritic cell (DC) densities were measured. Results Despite clinical improvement (TBUT: 6.4±1.2 s to 10.1±2.1 s, P=0.03; MGYLS: 3.5±0.8 glands to 7.0±1.1 glands, P=0.13) and a normal clinical examination post treatment, MGD patients remained symptomatic. IVCM revealed increased immune cells in the palpebral conjunctiva (refractory MGD EIC=592.6±110.1 cells/mm2; untreated MGD EIC=522.6±104.7 cells/mm2, P=0.69; responsive MGD EIC=194.9±119.4 cells/mm2, P<0.01; normals EIC=123.7±19.2 cells/mm2, P< 0.001), but not the cornea (refractory MGD DC=60.9±28.3 cells/mm2; normals DC=25.9±6.3 cells/mm2; P=0.43). EIC did not correlate with TBUT (Rs=−0.26, P=0.33). OSDI scores correlated with both EIC (Rs=0.76, P<0.001) and TBUT (Rs=−0.69, P<0.01) but not SIC. Intraglandular immune cells were also seen. Conclusion MGD-associated refractory symptoms and the symptom-sign disparity may be explained by clinically non-apparent, active inflammation of the palpebral conjunctiva as detected by IVCM. These patients may benefit from anti-inflammatory therapy. PMID:26088680

Effects of extracorporeal cardiopulmonary resuscitation on neurological and cardiac outcome after ischaemic refractory cardiac arrest.

PubMed

Cesana, Francesca; Avalli, Leonello; Garatti, Laura; Coppo, Anna; Righetti, Stefano; Calchera, Ivan; Scanziani, Elisabetta; Cozzolino, Paolo; Malafronte, Cristina; Mauro, Andrea; Soffici, Federica; Sulmina, Endrit; Bozzon, Veronica; Maggioni, Elena; Foti, Giuseppe; Achilli, Felice

2017-10-01

Extracorporeal cardiopulmonary resuscitation is increasingly recognised as a rescue therapy for refractory cardiac arrest, nevertheless data are scanty about its effects on neurologic and cardiac outcome. The aim of this study is to compare clinical outcome in patients with cardiac arrest of ischaemic origin (i.e. critical coronary plaque during angiography) and return of spontaneous circulation during conventional cardiopulmonary resuscitation vs refractory cardiac arrest patients needing extracorporeal cardiopulmonary resuscitation. Moreover, we tried to identify predictors of survival after successful cardiopulmonary resuscitation. We enrolled 148 patients with ischaemic cardiac arrest admitted to our hospital from 2011-2015. We compared clinical characteristics, cardiac arrest features, neurological and echocardiographic data obtained after return of spontaneous circulation (within 24 h, 15 days and six months). Patients in the extracorporeal cardiopulmonary resuscitation group ( n=63, 43%) were younger (59±9 vs 63±8 year-old, p=0.02) with lower incidence of atherosclerosis risk factors than those with conventional cardiopulmonary resuscitation. In the extracorporeal cardiopulmonary resuscitation group, left ventricular ejection fraction was lower than conventional cardiopulmonary resuscitation at early echocardiography (19±16% vs 37±11 p<0.01). Survivors in both groups showed similar left ventricular ejection fraction 15 days and 4-6 months after cardiac arrest (46±8% vs 49±10, 47±11% vs 45±13%, p not significant for both), despite a major extent and duration of cardiac ischaemia in extracorporeal cardiopulmonary resuscitation patients. At multivariate analysis, the total cardiac arrest time was the only independent predictor of survival. Extracorporeal cardiopulmonary resuscitation patients are younger and have less comorbidities than conventional cardiopulmonary resuscitation, but they have worse survival and lower early left ventricular ejection fraction. Survivors after extracorporeal cardiopulmonary resuscitation have a neurological outcome and recovery of heart function comparable to subjects with return of spontaneous circulation. Total cardiac arrest time is the only predictor of survival after cardiopulmonary resuscitation in both groups.

Assessment of the cardiac safety between cetuximab and panitumumab as single therapy in Chinese chemotherapy-refractory mCRC.

PubMed

Tang, Xue-Miao; Chen, Hao; Li, Qing; Song, Yiling; Zhang, Shuping; Xu, Xiao-Shuan; Xu, Yiwei; Chen, Shulin

2018-01-01

The cardiac safety of cetuximab and panitumumab, particularly as single agents, has not been investigated extensively. This trial was designed to specifically evaluate the cardiac safety of cetuximab and panitumumab as single therapy in Chinese chemotherapy-refractory metastatic colorectal cancer (mCRC) patients. Sixty-one patients received cetuximab at an initial dose of 400 mg/m 2 intravenously over 120 minutes on day 1 (week 1), followed by a maintenance dose of 250 mg/m 2 intravenously over 60 minutes on day 1 of each 7-day cycle. Forty-three patients received panitumumab at a dose of 6 mg/kg intravenously every 14 days. Routine laboratory tests and electrocardiogram (ECG) were performed at baseline, during therapy and after the treatment (4th and 10th months). The incidence of elevation of troponin I ultra (TNI Ultra), abnormal ECGs, cardiac events and noncardiac adverse events (AEs) were recorded and analyzed. The incidence of elevation of TNI Ultra between the two groups had no significance ( p =0.681), and TNI Ultra+ was observed more frequently in patients with metastases to more than three organs and they received fourth or above lines of chemotherapy. The most frequent abnormal ECG manifestations were nonspecific ST changes and QTc prolongation in the two groups. At 10 months after treatment, most of the abnormal ECG manifestations were reversed. The most common cardiac AEs of cetuximab and panitumumab included palpitations, dyspnea, chest pain and arrhythmias requiring treatment. Most of the events were mild and transient. The incidence of cardiac AEs had no significant difference between the two groups. Rash was still the most common noncardiac AE in both groups. Cetuximab and panitumumab showed favorable cardiac safety as single agents for Chinese chemotherapy-refractory mCRC patients. But monitoring for cardiac AEs is still necessary throughout the entire treatment process.

Experimental re-evaluation of flunarizine as add-on antiepileptic therapy.

PubMed

Thakur, Anamika; Sahai, A K; Thakur, J S

2011-04-01

Experimental studies have found several calcium channel blockers with anticonvulsant property. Flunarizine is one of the most potent calcium channel blockers, which has shown anticonvulsant effect against pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizures. However, further experimental and clinical trials have shown varied results. We conducted a PTZ model experimental study to re-evaluate the potential of flunarizine for add-on therapy in the management of refractory epilepsy. Experiments were conducted in PTZ model involving Swiss strain mice. Doses producing seizures in 50% and 99% mice, i.e. CD(50) and CD(99) values of PTZ were obtained from the dose-response study. Animals received graded, single dose of sodium valproate (100-300 mg/kg), lamotrigine (3-12 mg/kg) and flunarizine (5-20 mg/kg), and then each group of mice was injected with CD(99) dose of PTZ (65mg/kg i.p.). Another group of mice received single ED(50) dose (dose producing seizure protection in 50% mice) of sodium valproate and flunarizine separately in left and right side of abdomen. Results were analysed by Kruskal-Wallis ANOVA on Ranks test. As compared to control, sodium valproate at 250 mg/kg and 300 mg/kg produced statistical significant seizure protection. At none of the pre-treatment dose levels of lamotrigine, the seizure score with PTZ differed significantly from that observed in the vehicle-treated group. Pre-treatment with flunarizine demonstrated dose-dependent decrease in the seizure score to PTZ administration. As compared to control group, flunarizine at 20 mg/kg produced statistical significant seizure protection. As combined use of sodium valproate and flunarizine has shown significant seizure protection in PTZ model, flunarizine has a potential for add-on therapy in refractory cases of partial seizures. It is therefore, we conclude that further experimental studies and multicenter clinical trials involving large sample size are needed to establish flunarizine as add-on therapy in refractory epilepsy.

The Pluripotent Stem-Cell Marker Alkaline Phosphatase is Highly Expressed in Refractory Glioblastoma with DNA Hypomethylation.

PubMed

Iwadate, Yasuo; Suganami, Akiko; Tamura, Yutaka; Matsutani, Tomoo; Hirono, Seiichiro; Shinozaki, Natsuki; Hiwasa, Takaki; Takiguchi, Masaki; Saeki, Naokatsu

2017-02-01

Hypomethylation of genomic DNA induces stem-cell properties in cancer cells and contributes to the treatment resistance of various malignancies. To examine the correlation between the methylation status of stem-cell-related genes and the treatment outcomes in patients with glioblastoma (GBM). The genome-wide DNA methylation status was determined using HumanMethylation450 BeadChips, and the methylation status was compared between a group of patients with good prognosis (survival > 4 yr) and a group with poor prognosis (survival < 1 yr). Immunohistochemistry for proteins translated from hypomethylated genes, including alkaline phosphatase (ALPL), CD133, and CD44, was performed in 70 GBMs and 60 oligodendroglial tumors. The genomic DNA in refractory GBM was more hypomethylated than in GBM from patients with relatively long survival (P = .0111). Stem-cell-related genes including ALPL, CD133, and CD44 were also significantly hypomethylated. A validation study using immunohistochemistry showed that DNA hypomethylation was strongly correlated with high protein expression of ALPL, CD133, and CD44. GBM patients with short survival showed high expression of these stem-cell markers. Multivariate analysis confirmed that co-expression of ALPL + CD133 or ALPL + CD44 was a strong predictor of short survival. Anaplastic oligodendroglial tumors without isocitrate dehydrogenase 1 mutation were significantly correlated with high ALPL expression and poor survival. Accumulation of stem-cell properties due to aberrant DNA hypomethylation is associated with the refractory nature of GBM. Copyright © 2017 by the Congress of Neurological Surgeons

Clinical activity of everolimus in relapsed/refractory marginal zone B-cell lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group.

PubMed

Conconi, Annarita; Raderer, Markus; Franceschetti, Silvia; Devizzi, Liliana; Ferreri, Andrés J M; Magagnoli, Massimo; Arcaini, Luca; Zinzani, Pier Luigi; Martinelli, Giovanni; Vitolo, Umberto; Kiesewetter, Barbara; Porro, Elena; Stathis, Anastasios; Gaidano, Gianluca; Cavalli, Franco; Zucca, Emanuele

2014-07-01

The International Extranodal Lymphoma Study Group coordinated a phase II trial to evaluate the activity and safety of everolimus in marginal zone lymphomas (MZLs). Thirty patients with relapsed/refractory MZLs received everolimus for six cycles or until dose-limiting toxicity or progression. Median age was 71 years (range, 51-88 years). Twenty patients had extranodal, six splenic, four nodal MZL. Twenty-four patients had stage III-IV. Median number of prior therapies was two (range 1-5). Seventeen patients had early treatment discontinuation, in most cases due to toxicity. Median number of cycles was 4.5 (range, 1-16). Among the 24 assessable patients, the overall response rate (ORR) was 25% (95% confidence interval: 10-47). Grade 3-4 adverse events were neutropenia and thrombocytopenia (17% of patients, each), infections (17%), mucositis and odontogenic infections (13%) and lung toxicity (3%). The median response duration was 6.8 months (range, 1.4-11.1+). After a median follow-up of 14.5 months, five deaths were reported: four deaths were due to lymphoma, one was due to toxicity. In an intent-to-treat analysis, the projected median progression-free survival was 14 months. The moderate antitumour activity of everolimus in relapsed/refractory MZLs and the observed toxicity limit its therapeutical applicability in these indolent entities. Lower doses of the drug and, perhaps, different strategies including combination with additional agents need to be explored. © 2014 John Wiley & Sons Ltd.

Is there a decline in cognitive functions after combined electroconvulsive therapy and antipsychotic therapy in treatment-refractory schizophrenia?

PubMed

Pawełczyk, Agnieszka; Kołodziej-Kowalska, Emilia; Pawełczyk, Tomasz; Rabe-Jabłońska, Jolanta

2015-03-01

An analysis of literature shows that there is still little evidence concerning the efficacy of electroconvulsive therapy (ECT) combined with antipsychotic therapy in a group of treatment-resistant schizophrenia patients. More precisely, its influence on cognitive functions is still equivocal. The aim of this study was to assess the influence of ECT combined with antipsychotic therapy on working memory, attention, and executive functions in a group of treatment-refractory schizophrenia patients. Twenty-seven patients completed the study: 14 men and 13 women, aged 21 to 55 years (mean age, 32.8 years), diagnosed with treatment-resistant schizophrenia. Each patient underwent a course of ECT sessions and was treated with antipsychotic medications. Before the ECT and within 3 days after the last ECT session, the participants were assessed with the following neuropsychological tests: Trail Making Test (TMT) and Wisconsin Cart Sorting Test (WCST). There were no significant differences in the TMT and WCST results after combined ECT and antipsychotic therapy in treatment-refractory schizophrenia patients. According to the results of the neuropsychological tests, there was no decline in attention, executive functions, or working memory. The current study shows no significant difference in attention, working memory, or executive functions after treatment with a combination of electroconvulsive and antipsychotic therapy. This suggests that combined electroconvulsive therapy may not have a negative influence on the neuropsychological functioning of patients with treatment resistant schizophrenia.

Gaps and opportunities in refractory status epilepticus research in children: a multi-center approach by the Pediatric Status Epilepticus Research Group (pSERG).

PubMed

Sánchez Fernández, Iván; Abend, Nicholas S; Agadi, Satish; An, Sookee; Arya, Ravindra; Carpenter, Jessica L; Chapman, Kevin E; Gaillard, William D; Glauser, Tracy A; Goldstein, David B; Goldstein, Joshua L; Goodkin, Howard P; Hahn, Cecil D; Heinzen, Erin L; Mikati, Mohamad A; Peariso, Katrina; Pestian, John P; Ream, Margie; Riviello, James J; Tasker, Robert C; Williams, Korwyn; Loddenkemper, Tobias

2014-02-01

Status epilepticus (SE) is a life-threatening condition that can be refractory to initial treatment. Randomized controlled studies to guide treatment choices, especially beyond first-line drugs, are not available. This report summarizes the evidence that guides the management of refractory convulsive SE (RCSE) in children, defines gaps in our clinical knowledge and describes the development and works of the 'pediatric Status Epilepticus Research Group' (pSERG). A literature review was performed to evaluate current gaps in the pediatric SE and RCSE literature. In person and online meetings helped to develop and expand the pSERG network. The care of pediatric RCSE is largely based on extrapolations of limited evidence derived from adult literature and supplemented with case reports and case series in children. No comparative effectiveness trials have been performed in the pediatric population. Gaps in knowledge include risk factors for SE, biomarkers of SE and RCSE, second- and third-line treatment options, and long-term outcome. The care of children with RCSE is based on limited evidence. In order to address these knowledge gaps, the multicenter pSERG was established to facilitate prospective collection, analysis, and sharing of de-identified data and biological specimens from children with RCSE. These data will allow identification of treatment strategies associated with better outcomes and delineate evidence-based interventions to improve the care of children with SE. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Electromagnetic valve for controlling the flow of molten, magnetic material

DOEpatents

Richter, T.

1998-06-16

An electromagnetic valve for controlling the flow of molten, magnetic material is provided, which comprises an induction coil for generating a magnetic field in response to an applied alternating electrical current, a housing, and a refractory composite nozzle. The nozzle is comprised of an inner sleeve composed of an erosion resistant refractory material (e.g., a zirconia ceramic) through which molten, magnetic metal flows, a refractory outer shell, and an intermediate compressible refractory material, e.g., unset, high alumina, thermosetting mortar. The compressible refractory material is sandwiched between the inner sleeve and outer shell, and absorbs differential expansion stresses that develop within the nozzle due to extreme thermal gradients. The sandwiched layer of compressible refractory material prevents destructive cracks from developing in the refractory outer shell. 5 figs.

Electromagnetic valve for controlling the flow of molten, magnetic material

DOEpatents

Richter, Tomas

1998-01-01

An electromagnetic valve for controlling the flow of molten, magnetic material is provided, which comprises an induction coil for generating a magnetic field in response to an applied alternating electrical current, a housing, and a refractory composite nozzle. The nozzle is comprised of an inner sleeve composed of an erosion resistant refractory material (e.g., a zirconia ceramic) through which molten, magnetic metal flows, a refractory outer shell, and an intermediate compressible refractory material, e.g., unset, high alumina, thermosetting mortar. The compressible refractory material is sandwiched between the inner sleeve and outer shell, and absorbs differential expansion stresses that develop within the nozzle due to extreme thermal gradients. The sandwiched layer of compressible refractory material prevents destructive cracks from developing in the refractory outer shell.

Refractoriness in Sustained Visuo-Manual Control: Is the Refractory Duration Intrinsic or Does It Depend on External System Properties?

PubMed Central

van de Kamp, Cornelis; Gawthrop, Peter J.; Gollee, Henrik; Loram, Ian D.

2013-01-01

Researchers have previously adopted the double stimulus paradigm to study refractoriness in human neuromotor control. Currently, refractoriness, such as the Psychological Refractory Period (PRP) has only been quantified in discrete movement conditions. Whether refractoriness and the associated serial ballistic hypothesis generalises to sustained control tasks has remained open for more than sixty years. Recently, a method of analysis has been presented that quantifies refractoriness in sustained control tasks and discriminates intermittent (serial ballistic) from continuous control. Following our recent demonstration that continuous control of an unstable second order system (i.e. balancing a ‘virtual’ inverted pendulum through a joystick interface) is unnecessary, we ask whether refractoriness of substantial duration (∼200 ms) is evident in sustained visual-manual control of external systems. We ask whether the refractory duration (i) is physiologically intrinsic, (ii) depends upon system properties like the order (0, 1st, and 2nd) or stability, (iii) depends upon target jump direction (reversal, same direction). Thirteen participants used discrete movements (zero order system) as well as more sustained control activity (1st and 2nd order systems) to track unpredictable step-sequence targets. Results show a substantial refractory duration that depends upon system order (250, 350 and 550 ms for 0, 1st and 2nd order respectively, n = 13, p<0.05), but not stability. In sustained control refractoriness was only found when the target reverses direction. In the presence of time varying actuators, systems and constraints, we propose that central refractoriness is an appropriate control mechanism for accommodating online optimization delays within the neural circuitry including the more variable processing times of higher order (complex) input-output relations. PMID:23300430

An effective modestly intensive re-induction regimen with bortezomib in relapsed or refractory paediatric acute lymphoblastic leukaemia.

PubMed

Kaspers, Gertjan J L; Niewerth, Denise; Wilhelm, Bram A J; Scholte-van Houtem, Peggy; Lopez-Yurda, Marta; Berkhof, Johannes; Cloos, Jacqueline; de Haas, Valerie; Mathôt, Ron A; Attarbaschi, Andishe; Baruchel, André; de Bont, Eveline S; Fagioli, Franca; Rössig, Claudia; Klingebiel, Thomas; De Moerloose, Barbara; Nelken, Brigitte; Palumbo, Giuseppe; Reinhardt, Dirk; Rohrlich, Pierre-Simon; Simon, Pauline; von Stackelberg, Arend; Zwaan, Christian Michel

2018-05-01

This trial explored the efficacy of re-induction chemotherapy including bortezomib in paediatric relapsed/refractory acute lymphoblastic leukaemia. Patients were randomized 1:1 to bortezomib (1.3 mg/m 2 /dose) administered early or late to a dexamethasone and vincristine backbone. Both groups did not differ regarding peripheral blast count on day 8, the primary endpoint. After cycle 1, 8 of 25 (32%) patients achieved complete remission with incomplete blood count recovery, 7 (28%) a partial remission and 10 had treatment failure. Most common grade 3-4 toxicities were febrile neutropenia (31%) and pain (17%). Bortezomib was safely combined with vincristine. Bortezomib rarely penetrated the cerebrospinal fluid. © 2018 John Wiley & Sons Ltd.

Non-selective rapid electro-oxidation of persistent, refractory VOCs in industrial wastewater using a highly catalytic and dimensionally stable IrPd/Ti composite electrode.

PubMed

Cho, Wan-Cheol; Poo, Kyung-Min; Mohamed, Hend Omar; Kim, Tae-Nam; Kim, Yul-Seong; Hwang, Moon Hyun; Jung, Do-Won; Chae, Kyu-Jung

2018-05-11

Volatile organic compounds (VOCs) are highly toxic contaminants commonly dissolved in industrial wastewater. Therefore, treatment of VOC-containing wastewater requires a robust and rapid reaction because liquid VOCs can become volatile secondary pollutants. In this study, electro-oxidation with catalytic composite dimensionally stable anodes (DSAs)-a promising process for degrading organic pollutants-was applied to remove various VOCs (chloroform, benzene, toluene, and trichloroethylene). Excellent treatment efficiency of VOCs was demonstrated. To evaluate the VOC removal rate of each DSA, a titanium plate, a frequently used substratum, was coated with four different highly electrocatalytic composite materials (platinum group metals), Ir, IrPt, IrRu, and IrPd. Ir was used as a base catalyst to maintain the electrochemical stability of the anode. Current density and electrolyte concentration were evaluated over various ranges (20-45 mA/cm 2 and 0.01-0.15 mol/L as NaCl, respectively) to determine the optimum operating condition. Results indicated that chloroform was the most refractory VOC tested due to its robust chemical bond strength. Moreover, the optimum current density and electrolyte concentration were 25 mA/cm 2 and 0.05 M, respectively, representing the most cost-effective condition. Four DSAs were examined (Ir/Ti, IrPt/Ti, IrRu/Ti, and IrPd/Ti). The IrPd/Ti anode was the most suitable for treatment of VOCs presenting the highest chloroform removal performance of 78.8%, energy consumption of 0.38 kWh per unit mass (g) of oxidized chloroform, and the least volatilized fraction of 4.4%. IrPd/Ti was the most suitable anode material for VOC treatment because of its unique structure, high wettability, and high surface area. Copyright © 2018 Elsevier Ltd. All rights reserved.

Fludarabine Phosphate and Total Body Irradiation Followed by a Donor Peripheral Stem Cell Transplant in Treating Patients With Myelodysplastic Syndromes or Myeloproliferative Disorders

ClinicalTrials.gov

2018-03-28

Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Essential Thrombocythemia; Myeloproliferative Neoplasm; Paroxysmal Nocturnal Hemoglobinuria; Polycythemia Vera; Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase; Primary Myelofibrosis; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

Pembrolizumab and Vorinostat in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, or Hodgkin Lymphoma

ClinicalTrials.gov

2018-04-23

Grade 3a Follicular Lymphoma; Grade 3b Follicular Lymphoma; Recurrent Classical Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Classical Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma

Effect of Right Ventricular versus Biventricular Pacing on Electrical Remodeling in the Normal Heart

PubMed Central

Saba, Samir; Mehdi, Haider; Mathier, Michael A.; Islam, M. Zahadul; Salama, Guy; London, Barry

2010-01-01

Background Biventricular (BIV) pacing can improve cardiac function in heart failure by altering the mechanical and electrical substrates. We investigated the effect of BIV versus right ventricular (RV) pacing on the normal heart. Methods and Results Male New Zealand White rabbits (n=33) were divided into 3 groups: sham-operated (control), RV pacing, and BIV pacing groups. Four weeks after surgery, the native QT (p=0.004) interval was significantly shorter in the BIV group compared to the RV or sham-operated groups. Also, compared to rabbits in the RV group, rabbits in the BIV group had shorter RV ventricular effective refractory period (VERP) at all cycle lengths, and shorter LV paced QT interval during the drive train of stimuli and close to refractoriness (p<0.001 for all comparisons). Protein expression of the KVLQT1 was significantly increased in the BIV group compared to the RV and control groups, while protein expression of SCN5A and connexin43 was significantly decreased in the RV compared to the other study groups. Erg protein expression was significantly increased in both pacing groups compared to the controls. Conclusions In this rabbit model, we demonstrate a direct effect of BIV but not RV pacing on shortening the native QT interval as well as the paced QT interval during burst pacing and close to the VERP. These findings underscore the fact that the effect of BIV pacing is partially mediated through direct electrical remodeling and may have implications as to the effect of BIV pacing on arrhythmia incidence and burden. PMID:20042767

Electrophysiologic changes following treatment with organophosphorus-induced delayed neuropathy-producing agents in the adult hen.

PubMed

Robertson, D G; Schwab, B W; Sills, R D; Richardson, R J; Anderson, R J

1987-03-15

Although clinical, pathological, and biochemical effects of organophosphorus-induced delayed neuropathy (OPIDN) have been intensively investigated in the adult hen, detailed electrophysiological studies are lacking. Adult white leghorn hens were treated with a single oral dose of either 30 mg/kg tri-2-cresyl phosphate (TOCP), 750 mg/kg TOCP, 4 mg/kg di-n-butyl-2,2-dichlorovinyl phosphate (DBCV), or 30 mg/kg di-n-butyl-2,2-dichlorovinyl phosphinate (DBCV-P). The 750 mg/kg TOCP and DBCV, but not the 30 mg/kg TOCP and DBCV-P, treatments resulted in clinical signs of OPIDN and mild to marked damage of the tibial nerve 21 days after dose. Twenty-four hr lymphocyte neurotoxic esterase (NTE) inhibition was used as an index of brain NTE inhibition for the various organophosphorus compound (OP) treatment. Twenty-four hr lymphocyte NTE inhibition for 30 mg/kg TOCP, 750 mg/kg TOCP, DBCV, and DBCV-P was 54.1, 87.1, 84.8, and 68.3%, respectively. Twenty-one days after dose, the TOCP-treated hens exhibited some abnormalities in conduction velocity and action potential duration in the tibial or sciatic nerves. No abnormalities were observed in action potential parameters of either the DBCV or DBCV-P treatments. Neurotoxic OP (TOCP and DBCV) treatment resulted in decreased refractoriness in the tibial nerve, increased refractoriness in the sciatic nerve, and elevated strength duration threshold for both nerves. These changes were not present in nerves from DBCV-P (a non-neurotoxic NTE inhibitor)-treated hens. These results suggest that refractory period and strength duration abnormalities in peripheral nerve correlate well with the production of OPIDN and are evident without coincident clinical signs or histopathology.

Leading up to saying "yes": A qualitative study on the experience of patients with refractory epilepsy regarding presurgical investigation for resective surgery.

PubMed

Shih, Patti; Nikpour, Armin; Bleasel, Andrew; Herkes, Geoffrey; Mitchell, Rebecca; Seah, Rebecca; Mumford, Virginia; Braithwaite, Jeffrey; Vagholkar, Sanjyot; Rapport, Frances

2018-06-01

Adult patients with refractory epilepsy who are potential candidates for resective surgery undergo a period of presurgical investigation in tertiary epilepsy centers (TECs), where they engage extensively with healthcare professionals and receive a range of treatment-related information. This qualitative study aimed to examine the experiences of adult patients with refractory epilepsy leading up to and during presurgical investigation and how their perceptions of resective surgery are shaped. In-depth interviews with 12 patients and six epilepsy specialist clinicians and 12 observations of routine patient-clinician consultations took place at two TECs in Sydney, Australia. Data were thematically analyzed via group work. Patients reflected on prior experiences of poor seizure control and inadequate antiepileptic drug management and a lack of clarity about their condition before referral to tertiary care. Poor continuity of care and disrupted care transitions affected patients from regional locations. Tertiary referral increased engagement with personalized information about refractory epilepsy, which intensified during presurgical assessments with additional hospital visits and consultations. Experiential information, such as testimonials of other patients, influenced perceptions of surgery and fostered more trust and confidence towards healthcare professionals. Qualitative inquiry detailed multifaceted effects of information on patients' overall treatment trajectory and experience of healthcare. Earlier patient identification for surgical assessments should be accompanied by access to good quality information at primary and community care levels and strengthened referral processes. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Phase I trial and pharmacokinetic study of raltitrexed in children with recurrent or refractory leukemia: a pediatric oncology group study.

PubMed

Horton, Terzah M; Blaney, Susan M; Langevin, Anne-Marie; Kuhn, John; Kamen, Barton; Berg, Stacey L; Bernstein, Mark; Weitman, Steven

2005-03-01

To evaluate the toxicity, antileukemic activity, and pharmacology of raltitrexed administered weekly for 3 weeks to patients with refractory or recurrent leukemia. Raltitrexed was administered as a 15-minute infusion for 3 consecutive weeks every 5 weeks, at doses ranging from 1.3 to 2.8 mg/m(2). The first course was used to determine the dose-limiting toxicities and maximum tolerated dose. Correlative studies included an assessment of raltitrexed pharmacokinetics and measurement of plasma 2'-deoxyuridine concentrations, a surrogate measure of thymidylate synthase inhibition. Twenty-one children (18 evaluable) with refractory leukemia received 25 courses of raltitrexed. The dose-limiting toxicity was reversible elevation in liver transaminases at the 2.8-mg/m(2) dose level and the maximum tolerated dose was 2.1 mg/m(2) per dose. Pharmacokinetics were best characterized by a two-compartment model with a clearance of 139 mL/min/m(2) (8.3 L/h/m(2)), a 2.4-L volume of distribution, an initial half-life (t(1/2alpha)) of 6 minutes, and a terminal half-life (t(1/2beta)) of 45 minutes. There were three objective responses. Raltitrexed was well tolerated when administered as a single agent to children with recurrent or refractory leukemia. We observed preliminary evidence of antileukemia activity using this weekly dosing schedule and these observations support further evaluation of raltitrexed in this population.

Lunar bulk chemical composition: a post-Gravity Recovery and Interior Laboratory reassessment

PubMed Central

Taylor, G. Jeffrey; Wieczorek, Mark A.

2014-01-01

New estimates of the thickness of the lunar highlands crust based on data from the Gravity Recovery and Interior Laboratory mission, allow us to reassess the abundances of refractory elements in the Moon. Previous estimates of the Moon fall into two distinct groups: earthlike and a 50% enrichment in the Moon compared with the Earth. Revised crustal thicknesses and compositional information from remote sensing and lunar samples indicate that the crust contributes 1.13–1.85 wt% Al2O3 to the bulk Moon abundance. Mare basalt Al2O3 concentrations (8–10 wt%) and Al2O3 partitioning behaviour between melt and pyroxene during partial melting indicate mantle Al2O3 concentration in the range 1.3–3.1 wt%, depending on the relative amounts of pyroxene and olivine. Using crustal and mantle mass fractions, we show that that the Moon and the Earth most likely have the same (within 20%) concentrations of refractory elements. This allows us to use correlations between pairs of refractory and volatile elements to confirm that lunar abundances of moderately volatile elements such as K, Rb and Cs are depleted by 75% in the Moon compared with the Earth and that highly volatile elements, such as Tl and Cd, are depleted by 99%. The earthlike refractory abundances and depleted volatile abundances are strong constraints on lunar formation processes. PMID:25114309

Combination Therapies of Diacerein and Febuxostat Inhibit IL-1β Responses and Improve Clinical Symptoms in Patients With Refractory Gout.

PubMed

Yu, Yi-Kai; Yu, Fei; Ye, Cong; Shen, Gui-Fen; Lei, Xiao-Mei; Zhang, Sheng-Tao; Hu, Shao-Xian

2017-05-01

There are several therapeutic strategies available for the treatment of an acute gout attack and the prevention of recurrent gout flares, and they include nonsteroid anti-inflammatory drugs. This prospective study was aimed at evaluating the efficiency and safety of diacerein in combination with febuxostat on urate control, global assessments of disease activity, self-monitored gouty acute flare times, inflammatory markers, and clinical symptoms associated with their life quantity in patients with refractory gout. A total of 64 patients with refractory gout were sequentially recruited and prescribed with oral febuxostat alone or febuxostat plus diacerein daily for 12 weeks. The intensity of joint pain, numbers of acute flare, disease activity and the levels of serum amyloid A, mature IL-1β, IL-18, C-reactive protein, and urate in individual subjects were routine analyzed. In comparison with that treatment with febuxostat alone, treatment with both drugs for 12 weeks had a better therapeutic effect on reducing the values of visual analog scales, acute flares, and healthy assessment questionnaire scores in these gout patients. Furthermore, treatment with both drugs also significantly reduced the mean daily dose of etoricoxib and the levels of serum IL-1β and serum amyloid A. There was no significant difference in the frequency of patients with adverse effect between these 2 groups of patients. In conclusion, combination of diacerein and febuxostat had better therapeutic effect on reducing acute gout flares, inflammation, and clinical symptoms in patients with refractory gout.

Lunar bulk chemical composition: a post-Gravity Recovery and Interior Laboratory reassessment.

PubMed

Taylor, G Jeffrey; Wieczorek, Mark A

2014-09-13

New estimates of the thickness of the lunar highlands crust based on data from the Gravity Recovery and Interior Laboratory mission, allow us to reassess the abundances of refractory elements in the Moon. Previous estimates of the Moon fall into two distinct groups: earthlike and a 50% enrichment in the Moon compared with the Earth. Revised crustal thicknesses and compositional information from remote sensing and lunar samples indicate that the crust contributes 1.13-1.85 wt% Al2O3 to the bulk Moon abundance. Mare basalt Al2O3 concentrations (8-10 wt%) and Al2O3 partitioning behaviour between melt and pyroxene during partial melting indicate mantle Al2O3 concentration in the range 1.3-3.1 wt%, depending on the relative amounts of pyroxene and olivine. Using crustal and mantle mass fractions, we show that that the Moon and the Earth most likely have the same (within 20%) concentrations of refractory elements. This allows us to use correlations between pairs of refractory and volatile elements to confirm that lunar abundances of moderately volatile elements such as K, Rb and Cs are depleted by 75% in the Moon compared with the Earth and that highly volatile elements, such as Tl and Cd, are depleted by 99%. The earthlike refractory abundances and depleted volatile abundances are strong constraints on lunar formation processes. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Development of a patient decision aid for people with refractory angina: protocol for a three-phase pilot study

PubMed Central

2014-01-01

Background Refractory angina is a severe chronic disease, defined as angina which cannot be controlled by usual treatments for heart disease. This disease is frightening, debilitating, and difficult to manage. Many people suffering refractory have inadequate pain relief, continually revisit emergency departments for help, undergo repeated cardiac investigations, and struggle with obtaining appropriate care. There is no clear framework to help people understand the risks and benefits of available treatment options in Canada. Some treatments for refractory angina are invasive, while others are not covered by provincial health insurance plans. Effective care for refractory angina sufferers in Canada is critically underdeveloped; it is important that healthcare professionals and refractory angina sufferers alike understand the treatment options and their implications. This proposal builds on the recent Canadian practice guidelines for the management of refractory angina. We propose to develop a decision support tool in order to help people suffering from refractory angina make well-informed decisions about their healthcare and reduce their uncertainty about treatment options. Methods This project will be conducted in three phases: a) development of the support tool with input from clinical experts, the Canadian refractory angina guidelines, and people living with refractory angina, b) pilot testing of the usability of the tool, and c) formal preliminary evaluation of the effectiveness of the support tool to help people make informed decisions about treatment options. Discussion A decision support tool for refractory angina is needed and the available data suggest that by developing such a tool, we may be able to help refractory angina sufferers better understand their condition and the effectiveness of available treatment options (in their respective clinical settings) as well as their implications (e.g. risks vs. benefits). By virtue of this tool, we may also be able to facilitate identification and inclusion of patients’ values and preferences in the decision making process. This is particularly important as refractory angina is an intractable condition, necessitating that the selected course of treatment be lifelong. This study will yield a much needed patient decision aid for people living with refractory angina and pilot data to support a subsequent effectiveness study. PMID:24920518

Lenalidomide and Blinatumomab in Treating Patients With Relapsed Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-06-11

CD19 Positive; Mediastinal Lymphoma; Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Small Lymphocytic Lymphoma

Evaluation of Alternative Refractory Materials for the Main Flame Deflectors at KSC Launch Complexes

NASA Technical Reports Server (NTRS)

Calle, Luz Marina; Trejo, David; Rutkowsky, Justin

2006-01-01

The deterioration of the refractory materials used to protect the KSC launch complex steel base structures from the high temperatures during launches results in frequent and costly repairs and safety hazards. KSC-SPEC-P-0012, Specification for Refractory Concrete, is ineffective in qualifying refractory materials. This study of the specification and of alternative refractory materials recommends a complete revision of the specification and further investigation of materials that were found to withstand the environment of the Solid Rocket Booster main flame deflector better than the refractory materials in current use in terms of compressive strength, tensile strength, modulus of rupture, shrinkage, and abrasion.

Treating EGFR mutation resistance in non-small cell lung cancer - role of osimertinib.

PubMed

Mazza, Valentina; Cappuzzo, Federico

2017-01-01

The discovery of mutations in EGFR significantly changed the treatment paradigm of patients with EGFR -mutant non-small cell lung cancer (NSCLC), a particular group of patients with different clinical characteristics and outcome to EGFR -wild-type patients. In these patients, the treatment of choice as first-line therapy is first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, or afatinib. Inevitably, after the initial response, all patients become refractory to these drugs. The most common mechanism of acquired resistance to EGFR-TKIs is the development of a second mutation in exon 20 of EGFR ( T790M ). Osimertinib is a third-generation EGFR-TKI designed for overcoming T790M -mediated resistance. Based on the results of efficacy and tolerability of Phase II and Phase III studies, osimertinib has been approved for treatment of advanced EGFR T790M+ mutation NSCLC following progression on a prior EGFR-TKI. Occurrence of acquired resistance to osimertinib represents an urgent need for additional strategies including combination with other agents, such as other targeted therapies or checkpoint inhibitors, or development of new and more potent compounds.

Understanding refractory failures

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

Bases, G.J.

2006-01-15

Compared to most pieces of a power plant, refractory costs very little to install. Yet, if improperly manufactured, specified, stored, mixed installed, cured, or dried, refractory may cause problems that can significantly decrease a plant's operating efficiency and flexibility. Like Rodney Dangerfield, refractory design and installation deserve more respect. 4 photos.

Pembrolizumab and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

ClinicalTrials.gov

2018-05-22

Lymphocyte-Rich Classical Hodgkin Lymphoma; Recurrent Lymphocyte-Depleted Classical Hodgkin Lymphoma; Recurrent Mixed Cellularity Classical Hodgkin Lymphoma; Recurrent Nodular Sclerosis Classical Hodgkin Lymphoma; Refractory Lymphocyte-Depleted Classical Hodgkin Lymphoma; Refractory Mixed Cellularity Classical Hodgkin Lymphoma; Refractory Nodular Sclerosis Classical Hodgkin Lymphoma

Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

ClinicalTrials.gov

2017-11-15

Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma

TLK1 and Rad9 Cooperate in XRT-Refractory CaP

DTIC Science & Technology

2011-04-01

groups that are confirmatory of our work). Silencing of Tousled-like kinase 1 sensitizes cholangiocarcinoma cells to cisplatin-induced apoptosis... cholangiocarcinoma cells to cisplatin-induced apoptosis. Cancer Letters 2010;296:27–34. 10. De Benedetti A. Tousled kinase TLK1B mediates chromatin

The Evolution of the Protoplanetary Disk Recorded by Nucleosynthetic Isotope Variations of Variable Stellar Origin in Refractory Inclusions

NASA Astrophysics Data System (ADS)

Schönbächler, M.; Lai, Y.-J.; Henshall, T.; Fehr, M. A.; Cook, D. L.; Bullock, E. S.

2017-07-01

New CAI data confirm the homogeneous distribution of the short-lived p-process isotope 92Nb in the early solar system with the exception of CAIs with group II REE pattern that show increased 92Nb abundances.

Modification of surface properties of copper-refractory metal alloys

DOEpatents

Verhoeven, John D.; Gibson, Edwin D.

1993-10-12

The surface properties of copper-refractory metal (CU-RF) alloy bodies are modified by heat treatments which cause the refractory metal to form a coating on the exterior surfaces of the alloy body. The alloys have a copper matrix with particles or dendrites of the refractory metal dispersed therein, which may be niobium, vanadium, tantalum, chromium, molybdenum, or tungsten. The surface properties of the bodies are changed from those of copper to that of the refractory metal.

Reaction Behaviors of Al-Killed Medium-Manganese Steel with Different Refractories

NASA Astrophysics Data System (ADS)

Kong, Lingzhong; Deng, Zhiyin; Zhu, Miaoyong

2018-03-01

In order to understand the reaction mechanism between medium-manganese steel and different refractories, some laboratory experiments were carried out at 1873 K (1600 °C). Three types of refractory plates (Al2O3, MgO, and MgO·Al2O3) were used. The results show that Mn in liquid medium-manganese steel does not react easily with the Al2O3 refractory, but can react with the MgO refractory to generate a (Mn, Mg)O layer at the boundary between the refractory plate and liquid steel. After the formation of (Mn, Mg)O, a layer of (Mn, Mg)O·Al2O3 spinel is also formed at the edge of the MgO refractory. Similar to the MgO refractory, the dissolved Mn can react with the MgO·Al2O3 refractory as well, and a layer of (Mn, Mg)O·Al2O3 was also detected after reaction. It was found that the formation of (Mn, Mg)O·Al2O3 at the edge of the refractory is a source of (Mn, Mg)O·Al2O3 inclusions in liquid steel. The flush-off of the (Mn, Mg)O·Al2O3 layer would result in the formation of (Mn, Mg)O·Al2O3 inclusions.

Characterization of refractory brick based on local raw material from Lampung Province - Indonesia

NASA Astrophysics Data System (ADS)

Amin, Muhammad; Suryana, Yayat I.; Isnugroho, Kusno; Aji, Bramantyo B.; Birawidha, David C.; Hendronursito, Yusup

2018-04-01

Refractories are non-metallic inorganic materials that are difficult to melt at high temperatures and used in high-temperature casting industries. Refractories are classified into their constituent mineral feed stocks, refractories having typical plot properties commonly called fire bricks. In the manufacture of refractory bricks that exist in the market during the use of mangrove materials derived from abroad that is from China. In this research the refractory brick materials used are quartz sand, feldspart, kaolin, bentonite, and ball clay. All materials come from local Lampung Province - Indonesia. The experiment, there are 7 kinds of experimental composition, made of plot shape with size 230 mm, 65 mm in thickness, 114 mm height mould using manual press machine with 10 tons power and burning at 1400°C for 5 hours. Refractory brick product is done by physical test in the form of porosity, specific gravity, compressive strength and XRF and SEM characteristics. The result of XRF characteristic of refractory brick composition of 1 to 5 compared to the refractory brick type SK 34 in the market and the result of composition 1 is a composition close to refractory brick composition type SK 34 namely SiO2 is 54.21 %, Al2O3 is 25.38 % and test Physical of Bulk density is 2.25 g/cm3, porosity is 18.98 % and compressive strength is 325 kg/cm2.

Refractory Wear Mechanisms in the Nonferrous Metal Industry: Testing and Modeling Results

NASA Astrophysics Data System (ADS)

Gregurek, D.; Ressler, A.; Reiter, V.; Franzkowiak, A.; Spanring, A.; Prietl, T.

2013-11-01

Nonferrous pyrometallurgical processes today operate at a high intensity requiring the best standards for the furnace refractory systems. From one plant to another, there is a range of process conditions such as temperature, slag chemistry, and feed types, and each of these parameters can influence refractory life. It is generally understood that process changes at plants can impact refractory life. The ability to test and understand refractory responses to a wide range of furnace operating conditions is therefore important. The RHI Technology Centre in Leoben, Austria is well equipped with laboratory and pilot plant facilities to evaluate refractory suitability over the range of conditions encountered in modern nonferrous pyrometallurgical systems. This article describes refractory testing at the RHI Technology Centre of the impact of two metallurgical slags on a number of different RHI test bricks. The slags were a fayalite slag and a calcium ferrite slag supplied by two smelter plants. High-temperature corrosion tests were carried out in a 250-mm-diameter induction furnace and a 165-mm-diameter short rotary kiln; each unit was lined with a number of refractory bricks and tested against attack by the particular slag. After testing, the refractory bricks were subjected to several laboratory tests to determine the extent of corrosion. Optimal refractory choices for the customers' plants were developed based on the test results.

Reaction Behaviors of Al-Killed Medium-Manganese Steel with Different Refractories

NASA Astrophysics Data System (ADS)

Kong, Lingzhong; Deng, Zhiyin; Zhu, Miaoyong

2018-06-01

In order to understand the reaction mechanism between medium-manganese steel and different refractories, some laboratory experiments were carried out at 1873 K (1600 °C). Three types of refractory plates (Al2O3, MgO, and MgO·Al2O3) were used. The results show that Mn in liquid medium-manganese steel does not react easily with the Al2O3 refractory, but can react with the MgO refractory to generate a (Mn, Mg)O layer at the boundary between the refractory plate and liquid steel. After the formation of (Mn, Mg)O, a layer of (Mn, Mg)O·Al2O3 spinel is also formed at the edge of the MgO refractory. Similar to the MgO refractory, the dissolved Mn can react with the MgO·Al2O3 refractory as well, and a layer of (Mn, Mg)O·Al2O3 was also detected after reaction. It was found that the formation of (Mn, Mg)O·Al2O3 at the edge of the refractory is a source of (Mn, Mg)O·Al2O3 inclusions in liquid steel. The flush-off of the (Mn, Mg)O·Al2O3 layer would result in the formation of (Mn, Mg)O·Al2O3 inclusions.

Production and application of chemical fibers with special properties for manufacturing composite materials and goods of different usage

NASA Technical Reports Server (NTRS)

Levit, R.

1993-01-01

The development of modern technologies demands the creation of new nonmetallic, fibrous materials with specific properties. The fibers and materials developed by NII 'Chimvolokno', St. Petersburg, can be divided into two groups. The first group includes heat-resistant fibers, fire-resistant fibers, thermotropic fibers, fibers for medical application, and textile structures. The second group contains refractory fibers, chemoresistant and antifriction fibers, fibers on the basis of polyvinyl alcohol, microfiltering films, and paperlike and nonwoven materials. In cooperation with NPO 'Chimvolokno' MYTITSHI, we developed and started producing heat-resistant high-strength fibers on the base of polyhetarearilin and aromatic polyimides (SVM and terlon); heat-resistant fibers on the base of polyemede (aramid); fire-retardant fibers (togilen); chemoresistant and antifriction fibers on the basis of homo and copolymers of polytetrafluoroethylene (polyfen and ftorin); and water soluble, acetylated, and high-modulus fibers from polyvinyl alcohol (vylen). Separate reports will deal with textile structures and thermotropic fibers, as well as with medical fibers. One of the groups of refractory fibers carbon fibers (CF) and the corresponding paperlike nonwoven materials are discussed in detail. Also, composite materials (CM) and their base, which is the subject of the author's research since 1968, is discussed.

Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML

ClinicalTrials.gov

2018-03-05

Relapsed Acute Lymphoblastic Leukemia (ALL); Refractory Acute Lymphoblastic Leukemia (ALL); Relapsed Acute Myelogenous Leukemia (AML); Refractory Acute Myelogenous Leukemia (AML); Relapsed Mixed Lineage Leukemia; Refractory Mixed Lineage Leukemia; Relapsed Biphenotypic Leukemia; Refractory Biphenotypic Leukemia; Chronic Myelogenous Leukemia (CML) in Blast Crisis

Onalespib in Treating Patients With Relapsed or Refractory Anaplastic Large Cell Lymphoma, Mantle Cell Lymphoma, or Diffuse Large B-Cell Lymphoma

ClinicalTrials.gov

2018-05-23

ALK Positive; BCL6 Positive; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma

High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

ClinicalTrials.gov

2018-02-28

Acute Leukemia of Ambiguous Lineage; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies

ClinicalTrials.gov

2018-05-22

Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma

High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma

ClinicalTrials.gov

2017-12-04

Post-Transplant Lymphoproliferative Disorder; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

A novel approach to restore atrial function after the maze procedure in patients with an enlarged left atrium.

PubMed

Marui, Akira; Tambara, Keiichi; Tadamura, Eiji; Saji, Yoshiaki; Sasahashi, Nozomu; Ikeda, Tadashi; Nishina, Takeshi; Komeda, Masashi

2007-08-01

Left atrial (LA) volume reduction surgery concomitant with the maze procedure has been reported to facilitate sinus rhythm recovery even in patients with refractory atrial fibrillation (AF) with an enlarged LA. However, it is unknown whether the procedures can also restore effective atrial function of the enlarged LA with over-stretched myocardium. The maze procedures in association with mitral valve surgery were performed to 57 AF patients with an enlarged LA (LA diameter >or=60mm). Among them, 32 patients had concomitant LA volume reduction surgery (VR group). Another 25 patients did not have the volume reduction (control group). Three months postoperatively LA end-diastolic volume (LAEDV, ml) assessed by magnetic resonance (MR) imaging was larger in the VR group than that in the control group (291+/-117 vs 223+/-81 ml, p<0.05). Postoperatively, sinus rhythm recovery rate was better (84 vs 68%, p<0.05) and LAEDV was drastically smaller (118+/-48 vs 203+/-76 ml, p<0.001) in the VR group than those in the control group. Among the patients with sinus rhythm recovery in both groups, LA contraction ejection fraction (%) improved in the VR group but not in the control group (22.3+/-7.8 vs 10.3+/-4.7%, p<0.001). The LA volume reduction surgery concomitant with the maze procedure restored contraction of the enlarged LA; however, the maze procedure alone did not restore LA contraction in spite of successful sinus rhythm recovery. LA volume reduction surgery may be desirable to the patients with refractory AF with over-stretched LA.

Design and development of advanced castable refractory materials

NASA Astrophysics Data System (ADS)

Davis, Robert Bruce

New formulations of castable refractory composite materials were studied. This technology is used to produce low cost composite concrete structures designed for high temperature stability, superior wear resistance and improved strength. An in situ fired, castable cement installation is a heterogeneous structure divided into three zones according to the temperature history and microstructure. The properties of each zone depend on the predominant bonding mode between constituents. Each zone has a characteristic microstructure that influences the integrity of the monolith. The hot side may have a highly dense and developed network of ceramic bonds between constituent particles while the cold side may never reach temperatures sufficient to drive off free water. The thermal, structural and tribological properties depend on the microstructure and the type of bonding that holds the monolith together. The phase distributions are defined by sets of metastable phase conditions driven by the local hydrated chemistry, nearest neighbor oxide compounds, impurities and sintering temperature. Equilibrium phase diagrams were used to select optimum compositions based on higher melting point phases. The phase diagrams were also used to target high temperature phase fields that are stable over wide temperature and stoichiometric ranges. Materials selection of candidate hydraulic clinkers, high temperature oxides, and reinforcement phases were based on requirements for high temperature stability. The calcium aluminate (CaO-Al2O3) and calcium dialuminate (CaO-(Al2O3)2) are common refractory clinkers used in castable refractory cements. The thermodynamics and kinetics of cement hydrate formation are well studied and suited to become the building block of a design for a superior refractory castable cement. The inert oxides mixed with the calcium aluminate clinkers are magnesia (MgO), alumina (Al 2O3), spinel (MgAl2O4) and chromic (Cr2O3). The bulk of the experiments concentrated in the Al2O3--MgO--CaO ternary system. Materials selection criteria for reinforcement materials was based on improved high temperature stability, increased strength, reduced thermal expansion mismatch, low thermal conductivity and increasing wear resistance. The reinforcement phases selected for this investigation are zircon (ZrSiO4), zirconia (ZrO2), spinel (MgAl2O4) and dead burnt magnesia (MgO). Batches of the formulations were tested for thermal conductivity, wear resistance and mechanical strength. Relative rankings of the formulations against commercial products indicate improved or similar performance with increased maximum temperature limits and improved thermal insulating power. The new cement formulations proved to exhibit superior high temperature stability with an increasing volume fraction of high temperature oxides. The addition of reinforcement aggregates and powder sizing to offset the loss of strength. The room temperature compression strength and wear resistance of the optimized formulations exceeded the properties of conventional refractory, brick and castable cement tested concurrently.

Genotype–phenotype correlation among beta-thalassemia and beta-thalassemia/HbE disease in Thai children: predictable clinical spectrum using genotypic analysis

PubMed Central

Traivaree, Chanchai; Monsereenusorn, Chalinee; Rujkijyanont, Piya; Prasertsin, Warakorn; Boonyawat, Boonchai

2018-01-01

Introduction Beta-thalassemia is a group of inherited hemolytic anemias and one of the most common genetic disorders in Thailand. The clinical spectrum of beta-thalassemia disease ranges from mild to severe clinical symptoms including mild beta-thalassemia intermedia (TI) and severe beta-thalassemia major (TM). Objective This study aimed to determine the correlation between beta-globin gene (HBB) mutations and their phenotypic manifestations by evaluating patients’ clinical characteristics, transfusion requirements, growth and hematologic parameters, and hemoglobin typing among pediatric patients treated at Phramongkutklao Hospital. Materials and methods Seventy beta-thalassemia patients, including 63 with beta-thalassemia/hemoglobin E (HbE) and 7 with either homozygous or compound heterozygous beta-thalassemia, were enrolled in this study. Their clinical presentation, growth parameters and laboratory findings were reviewed and analyzed. The mean follow-up time was 10.52±5.62 years. Mutation analysis in each individual was performed using multiplex amplification refractory mutation system (M-ARMS), direct DNA sequencing of beta-globin gene and gap PCR for 3.4 kb deletion detection. Results All 7 homozygous and compound heterozygous beta-thalassemia patients were classified in TM. Among 63 patients with beta-thalassemia/HbE, 58 were classified in TM and 4 were classified in TI. Mean age at diagnosis was 0.8±0.49 years for homozygous or compound heterozygous beta-thalassemia and 3.43±3.5 years for beta-thalassemia/HbE. The most common HBB mutation was HBB:c.126_129delCTTT [codon 41/42 (-TCTT)] found in 34 alleles (48.6%). The height for age was also lower in homozygous beta-thalassemia patients (<3rd percentile) compared to compound heterozygous beta-thalassemia patients (25–50th percentile). Conclusion This study revealed a genotype–phenotype correlation of the most prevalent beta-thalassemia in Thai children using diagnostic capacity in genotypic analysis of HBB mutation. Our findings can provide a better prediction of clinical manifestation and severity by early identification of the type of the HBB mutations. PMID:29695942

Determinants and predictors of outcome in super refractory status epilepticus--a developing country perspective.

PubMed

Jayalakshmi, Sita; Ruikar, Devashish; Vooturi, Sudhindra; Alladi, Suvarna; Sahu, Sambit; Kaul, Subhash; Mohandas, Surath

2014-11-01

Super refractory status epilepticus (SRSE) is a recent entity. There is limited information about the etiology and outcome of SRSE from developing countries. We evaluated determinants and predictors of outcome in patients with convulsive SRSE in Indian population. In this open cohort study, data of patients with convulsive SE admitted in neurointensive care unit (NICU) from 2005 to 2013 was retrospectively analyzed. Regression and survival analysis was done for outcome of patients divided into non refractory SE (NRSE), refractory SE (RSE), and SRSE groups. The primary outcome for analysis was in hospital mortality. Also functional outcome at 6 months was graded according to the Glasgow outcome scale (GOS), and classified as good (GOS 4 and 5) and poor (GOS 1, 2 and 3) outcome groups. Out of 177 patients with SE, 105 (59.3%) had NRSE; 72 (40.7%) had RSE of which 30 (16.9% of 177) were sub-classified as SRSE. SRSE was frequent (39%) in children (p<0.01), elderly (21.7%; p<0.003), and in incident SE (82.1%, p=0.05). Encephalitis was the commonest etiology in RSE (30.9%, p=0.015), SRSE (66.7%, p<0.001) than NRSE (12.3%). Encephalitis (β=8.250 (1.8-37.82); p=0.007) was the determinant of the progression of SE to SRSE. Overall mortality was 19.2%, highest in SRSE (40.0%) followed by RSE (35.7%), both significantly (p<0.001) higher than NRSE (6.7%). Mortality was high in patients with encephalitis than other etiologies (39.1% vs. 12.1%; p=0.001). Acidosis predicted mortality in the entire cohort (β=7.313 (1.6-32.58); p=0.009); however none of the variables predicted mortality in SRSE patients. At 6 months follow up only 33.3% of patients with SRSE were in GOS good outcome group when compared to RSE (33.3% vs. 57.1%; p=0.055), and NRSE (33.3% vs. 79.1%; p<0.0001). SRSE is common in children, elderly, and incident SE. Encephalitis was the determinant of progression of SE to SRSE. None of the variables predicted mortality in SRSE patients. Sixty percent of patients with SRSE survived and one third had good outcome. Therefore one should continue the care inspite of weeks of SE. Copyright © 2014 Elsevier B.V. All rights reserved.

d,l-Sotalol reverses abbreviated atrial refractoriness and prevents promotion of atrial fibrillation in a canine model with left ventricular dysfunction induced by atrial tachypacing.

PubMed

Sakamoto, Tamotsu; Fujiki, Akira; Nakatani, Yosuke; Sakabe, Masao; Mizumaki, Koichi; Hashimoto, Norio; Inoue, Hiroshi

2009-10-01

This study evaluated antiarrhythmic effects of d,l-sotalol in a canine atrial fibrillation (AF) model with left ventricular dysfunction. Thirteen beagles (Sotalol group n=7 and Control group n=6) were subjected to atrial tachypacing (ATP) (400 beats/min) with intact atrioventricular conduction for 4 weeks. Oral d,l-sotalol (2 mg/kg) was administered 1 week after starting ATP and continued throughout the experiment. One week after starting ATP, atrial effective refractory periods (AERPs) were shortened in both groups. However, d,l-sotalol treatment gradually prolonged AERP, resulting in a significant prolongation of AERP compared with the Control group at 4 weeks (Control 76 +/-4 and Sotalol 126 +/-5 ms, p<0.01). d,l-Sotalol treatment showed lower AF inducibility and shorter AF duration at 4 weeks. In the control group, expressions of L-type Ca(2+) channel alpha1c and Kv4.3 mRNA were downregulated by 46.2% and 43.0%, respectively, after 4 weeks of ATP; d,l-sotalol treatment did not affect these changes. d,l-Sotalol treatment prolonged AERP, even after atrial electrical remodeling had developed, and prevented AF perpetuation without affecting downregulated expression of L-type Ca(2+) channel alpha1c and Kv4.3 mRNA in an ATP-induced canine AF model.

Refractory thermowell for continuous high temperature measurement of molten metal

DOEpatents

Thiesen, Todd J.

1992-01-01

An apparatus for the continuous high temperature measurement of materials in vessels lined with rammed or cast refractory materials. A refractory housing member is integral with the refractory lining of the vessel and contains a plurality of high temperature sensing means, such as thermocouples. A face of the housing is flush with the refractory lining and contacts the high temperature material contained in the vessel. Continuous temperature measurement is achieved by a means which is coupled to the thermocouples for indicating the temperature.

Diagnosis and management of refractory celiac disease: a systematic review.

PubMed

Labidi, Asma; Serghini, Meriem; Karoui, Sami; Boubaker, Jalel; Filali, Azza

2013-01-01

Refractory celiac disease is defined by persisting malabsorptive symptoms in spite of a strict gluten free diet for at least 6 to 12 months. Alternatives to gluten free diet seem to be still controversial. To describe the clinical and epidemiologic aspects of refractory celiac disease, and to identify therapeutic options in this condition. Systematic review and critical analysis of observational studies, clinical trials and case reports that focused on diagnosis and management of refractory celiac disease. Refractory celiac disease can be classified as type 1 or type 2 according to the phenotype of intraepithelial lymphocytes. Great complications such as enteropathy-associated T-cell lymphoma may occur in a subgroup of these patients mainly in refractory celiac disease type 2. Curative therapies are still lacking. Refractory celiac disease remains a diagnosis of exclusion. Its prognosis remains still dismal by the absence yet of curative therapies. However, some new treatments seem to hold promise during few cohort-studies.

Refractory metals for ARPS AMTEC cells

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

Svedberg, R.C.; Sievers, R.C.

1998-07-01

Alkali Metal Thermal-to-Electric Converter (AMTEC) cells for the Advanced Radioisotope Power Systems (ARPS) program are being developed with refractory metals and alloys as the basic structural materials. AMTEC cell efficiency increases with cell operating temperature. For space applications, long term reliability and high efficiency are essential and refractory metals were selected because of their high temperature strength, low vapor pressure, and compatibility with sodium. However, refractory metals are sensitive to oxygen, nitrogen and hydrogen contamination and refractory metal cells cannot be processed in air. Because of this sensitivity, new manufacturing and processing techniques are being developed. In addition to structuralmore » elements, development of other refractory metal components for the AMTEC cells, such as the artery and evaporator wicks, pinchoff tubes and feedthroughs are required. Changes in cell fabrication techniques and processing procedures being implemented to manufacture refractory metal cells are discussed.« less

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 efficacy end points. The rate of grade 3 or 4 neutropenia was higher in the venetoclax-rituximab group than in the bendamustine-rituximab group, but the rates of grade 3 or 4 febrile neutropenia and infections or infestations were lower with venetoclax than with bendamustine. The rate of grade 3 or 4 tumor lysis syndrome in the venetoclax-rituximab group was 3.1% (6 of 194 patients). Among patients with relapsed or refractory chronic lymphocytic leukemia, venetoclax plus rituximab resulted in significantly higher rates of progression-free survival than bendamustine plus rituximab. (Funded by Genentech and AbbVie; ClinicalTrials.gov number, NCT02005471 .).

Effects of Qishe Pill, a compound traditional Chinese herbal medicine, on cervical radiculopathy: study protocol for a randomized controlled trial.

PubMed

Cui, Xue-Jun; Sun, Yue-Li; You, Sheng-Fu; Mo, Wen; Lu, Sheng; Shi, Qi; Wang, Yong-Jun

2013-10-07

Neck pain is a common symptom in most patients suffering from cervical radiculopathy. However, some conservative treatments are limited by their modest effectiveness. On the other hand, surgical intervention for cervical disc disorders is indicated when symptoms are refractory to conservative treatments and neurological symptoms are progressive. Many patients use complementary and alternative medicine, including traditional Chinese medicine, to address their symptoms. The purpose of the present study is to examine the efficacy and safety of Qishe Pill, a compound traditional Chinese herbal medicine, for neck pain in patients with cervical radiculopathy. A multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of the Qishe Pill is proposed. The study will include 240 patients from five sites across China and diagnosed with cervical radiculopathy, according to the following inclusion criteria: age 18 to 65 with pain or stiffness in the neck for at least 2 weeks (neck disability index score 25 or more) and accompanying arm pain that radiates distally from the elbow. Qualified participants will be randomly allocated into two groups: Qishe Pill group and placebo group. The prescription of the trial medications (Qishe Pill/placebo) are 3.75 g each twice a day for 28 consecutive days. The primary outcome is pain severity. Secondary outcomes are functional status, patient satisfaction, and adverse events as reported in the trial. Qishe Pill is composed of processed Radix Astragali, Muscone, Szechuan Lovage Rhizome, Radix Stephaniae Tetrandrae, Ovientvine, and Calculus Bovis Artifactus. According to modern research and preparation standards, Qishe Pill is developed to improve on the various symptoms of cervical radiculopathy, especially for neck pain. As it has a potential benefit in treating patients with neck pain, we designed a double-blind, prospective, randomized-controlled trial and would like to publish the results and conclusions later. If Qishe Pill can alleviate neck pain without adverse effects, it may be a unique strategy for the treatment of cervical radiculopathy. This study is registered at ClinicalTrials.gov, NCT01274936.

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

Scrudato, R.J.; Chiarenzelli, J.R.

An electrochemical peroxidation (ECP) process has been developed and used to degrade polychlorinated biphenyls (PCB) and volatile organic compounds (VOC)-contaminated water, sludge, and sediments at a New York State Federal and State Superfund Site. The process involves passing an oscillating low-amperage (<10 amps) current through steel electrodes immersed in an acidified water or sediment slurry into which hydrogen peroxide (<1,000 ppm) is added. The generated free radicals attack organic compounds, including organo-metallic complexes and refractory compounds including PCBs. PCB degradation ranged from about 30% to 80% in experiments involving Federal Superfund Site sediments; total PCBs were reduced by {approximately}97% tomore » 68%, respectively, in water and slurry collected from a State Superfund subsurface storage tank. VOC bench-scale experiments involved chloroethane, 1,1-dichloroethane, dichloromethane, 1,1,1-trichloroethane, and acetone and after a 3-min ECP treatment, degradation ranged from >94% to about 99.9%. Results indicate the ECP is a viable process to degrade organic contaminants in water and sediment suspensions. Because the treated water suspensions are acidified, select trace metal sorbed to the particulates is solubilized and therefore can be segregated from the particulates, offering a process that simultaneously degrades organic contaminants and separates trace metals. 19 refs., 1 fig., 4 tabs.« less

The Production of Complex Organics from Interstellar Ices

NASA Technical Reports Server (NTRS)

Sandford, Scott A.; Allamandola, Louis; Bernstein, Max; Deamer, David; Dworkin, Jason; Zare, Richard

2001-01-01

Infrared spectroscopy of ices in interstellar dense molecular clouds has shown that they contain a variety of simple molecules, as well as aromatic hydrocarbons. While in these clouds, these ices are processed by ultraviolet light and cosmic rays. High vacuum, UV irradiation laboratory simulations conducted using various realistic approx. 10 K interstellar mixed-molecular ice analogs, both with and without polycyclic aromatic hydrocarbons (PAHs), have been carried out in NASA-Ames' Astrochemistry Laboratory. Upon warming, these irradiated ices are found to produce refractory organic residues. These residues have been analyzed using a variety of techniques, including HPLC and laser desorption mass spectrometry, and they have been shown to contain a variety of complex organic compounds. Several of these compounds may be of prebiotic significance. In particular, we will discuss the detection of quinones (substituted PAHs that are used by living systems for electron transport) and amphiphiles (molecules that self-assemble to form membranes). Laboratory simulations have also demonstrated that the organic products can show isotopic enrichments in D that provide clues for the mechanisms of their formation. Similar compounds and D enrichments are seen in the organics found in primitive meteorites, suggesting a direct link between interstellar chemistry and the delivery of organics to newly formed planets.

Discovery of 2,4-diarylaminopyrimidines bearing a resorcinol motif as novel ALK inhibitors to overcome the G1202R resistant mutation.

PubMed

Geng, Kaijun; Xia, Zongjun; Ji, Yinchun; Zhang, Ruisi Ruthy; Sun, Deqiao; Ai, Jing; Song, Zilan; Geng, Meiyu; Zhang, Ao

2018-01-20

To address drug resistance caused by ALK kinase mutations, especially the most refractory and predominant mutation G1202R for the second-generation ALK inhibitor, a series of new diarylaminopyrimidine analogues were designed by incorporating a resorcinol moiety (A-ring) to interact the ALK kinase domain where the G1202R is located. Compound 12d turns out as the most potent with IC 50 values of 1.7, 3.5, and 1.8 nM against ALK wild type, gatekeeper mutant L1196M, and the G1202R mutant, respectively. More importantly, compound 12d has excellent inhibitory effects against the proliferation of BaF3 cells specifically expressing ALK wild type, gatekeeper L1196M, and the most challenging mutant G1202R, with IC 50 values all less than 1.5 nM. Collectively, compound 12d is worthy of further investigation as a new more potent third-generation ALK inhibitor to circumvent drug resistance of both the first-generation and the second-generation inhibitors. Copyright © 2017. Published by Elsevier Masson SAS.

Refractory Organic Compounds in Enceladus' Ice Grains and Hydrothermal Activity

NASA Astrophysics Data System (ADS)

Postberg, F.; Khawaja, N.; Hsu, H. W.; Sekine, Y.; Shibuya, T.

2015-12-01

Cassini's Cosmic Dust Analyzer (CDA) generates time-of-flight mass spectra of individual grains impinging on the instruments target-plate. Following the analysis of salt rich ice grains emitted by Enceladus that indicated a salt-water ocean in contact with the moon's rocky core [1,2] a recent CDA analysis of nano-phase silica particles pointed at hydrothermal activity at the moon's rock/water interface [3]. The results imply temperatures above 80 - 90°C and alkaline pH values around 10 reminiscent of alkaline hydrothermal vents on Earth like the Lost City Hydrothermal Field. In this context the compositional analysis of organic components in CDA mass spectra of the ejected ice grains is of particular relevance. A multitude of volatile organic species has already been identified in the gas component of the plume [4]. As expected, we find more complex organic molecules in ice grains than in the gas indicating aromatic species, amines, and carbonyl group species. The composition of organic-bearing ice grains displays a great diversity indicating a variety of different organic species in varying concentrations. Recent spatially resolved CDA in situ measurements inside Enceladus' plume indicate that these organic compounds are especially frequent in 'young' ice grains that have just been ejected by high velocity jets. We investigate the implications of our findings with respect to ice grain formation at the water surface and inside the icy vents. We constrain the generation of organic compounds at the rock/water interface in the light of hydrothermal activity and the potential for the formation of life precursor molecules in Enceladus' ocean. Ref:[1] Postberg et al., Nature 459, 1098-1101 (2009). [2] Postberg et al., Nature 474, 620-622 (2011). [3]. Hsu, Postberg, Sekine et al., Nature, 519, 207-210 (2015). [4] Waite et al., Nature 460, 487-490 (2009).

Structure-based manual screening and automatic networking for systematically exploring sansanmycin analogues using high performance liquid chromatography tandem mass spectroscopy.

PubMed

Jiang, Zhi-Bo; Ren, Wei-Cong; Shi, Yuan-Yuan; Li, Xing-Xing; Lei, Xuan; Fan, Jia-Hui; Zhang, Cong; Gu, Ren-Jie; Wang, Li-Fei; Xie, Yun-Ying; Hong, Bin

2018-05-18

Sansanmycins (SS), one of several known uridyl peptide antibiotics (UPAs) possessing a unique chemical scaffold, showed a good inhibitory effect on the highly refractory pathogens Pseudomonas aeruginosa and Mycobacterium tuberculosis, especially on the multi-drug resistant M. tuberculosis. This study employed high performance liquid chromatography-mass spectrometry detector (HPLC-MSD) ion trap and LTQ orbitrap tandem mass spectrometry (MS/MS) to explore sansanmycin analogues manually and automatically by re-analysis of the Streptomyces sp. SS fermentation broth. The structure-based manual screening method, based on analysis of the fragmentation pathway of known UPAs and on comparisons of the MS/MS spectra with that of sansanmycin A (SS-A), resulted in identifying twenty sansanmycin analogues, including twelve new structures (1-12). Furthermore, to deeply explore sansanmycin analogues, we utilized a GNPS based molecular networking workflow to re-analyze the HPLC-MS/MS data automatically. As a result, eight more new sansanmycins (13-20) were discovered. Compound 1 was discovered to lose two amino acids of residue 1 (AA 1 ) and (2S, 3S)-N 3 -methyl-2,3-diamino butyric acid (DABA) from the N-terminus, and compounds 6, 11 and 12 were found to contain a 2',3'-dehydrated 4',5'-enamine-3'-deoxyuridyl moiety, which have not been reported before. Interestingly, three trace components with novel 5,6-dihydro-5'-aminouridyl group (16-18) were detected for the first time in the sansanmycin-producing strain. Their structures were primarily determined by detail analysis of the data from MS/MS. Compounds 8 and 10 were further confirmed by nuclear magnetic resonance (NMR) data, which proved the efficiency and accuracy of the method of HPLC-MS/MS for exploration of novel UPAs. Comparing to manual screening, the networking method can provide systematic visualization results. Manual screening and networking method may complement with each other to facilitate the mining of novel UPAs. Copyright © 2018 Elsevier B.V. All rights reserved.

Marine actinomycetes: a new source of compounds against the human malaria parasite.

PubMed

Prudhomme, Jacques; McDaniel, Eric; Ponts, Nadia; Bertani, Stéphane; Fenical, William; Jensen, Paul; Le Roch, Karine

2008-06-04

Malaria continues to be a devastating parasitic disease that causes the death of 2 million individuals annually. The increase in multi-drug resistance together with the absence of an efficient vaccine hastens the need for speedy and comprehensive antimalarial drug discovery and development. Throughout history, traditional herbal remedies or natural products have been a reliable source of antimalarial agents, e.g. quinine and artemisinin. Today, one emerging source of small molecule drug leads is the world's oceans. Included among the source of marine natural products are marine microorganisms such as the recently described actinomycete. Members of the genus Salinispora have yielded a wealth of new secondary metabolites including salinosporamide A, a molecule currently advancing through clinical trials as an anticancer agent. Because of the biological activity of metabolites being isolated from marine microorganisms, our group became interested in exploring the potential efficacy of these compounds against the malaria parasite. We screened 80 bacterial crude extracts for their activity against malaria growth. We established that the pure compound, salinosporamide A, produced by the marine actinomycete, Salinispora tropica, shows strong inhibitory activity against the erythrocytic stages of the parasite cycle. Biochemical experiments support the likely inhibition of the parasite 20S proteasome. Crystal structure modeling of salinosporamide A and the parasite catalytic 20S subunit further confirm this hypothesis. Ultimately we showed that salinosporamide A protected mice against deadly malaria infection when administered at an extremely low dosage. These findings underline the potential of secondary metabolites, derived from marine microorganisms, to inhibit Plasmodium growth. More specifically, we highlight the effect of proteasome inhibitors such as salinosporamide A on in vitro and in vivo parasite development. Salinosporamide A (NPI-0052) now being advanced to phase I trials for the treatment of refractory multiple myeloma will need to be further explored to evaluate the safety profile for its use against malaria.

Durvalumab With or Without Lenalidomide in Treating Patients With Relapsed or Refractory Cutaneous or Peripheral T Cell Lymphoma

ClinicalTrials.gov

2018-04-06

Folliculotropic Mycosis Fungoides; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified; Sezary Syndrome; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma

Refractory Hodgkin lymphoma.

PubMed

von Tresckow, Bastian; Engert, Andreas

2013-09-01

Despite the advances in the treatment of Hodgkin Lymphoma, patients with refractory disease still have a poor prognosis. Hodgkin Lymphoma can be refractory at first diagnosis or might become refractory later in the course of treatment. Both situations represent a therapeutic challenge. Intensified chemotherapy with BEACOPP escalated has been evaluated in early unfavourable and advanced Hodgkin Lymphoma and led to an improved tumour control and reduced rates of refractory disease. Furthermore, there is growing evidence for the role of tandem autologous transplant in breaking refractory disease. For patients relapsing after autologous transplant, more recent analyses have reported outcome and defined risk factors. The antibody drug conjugate brentuximab vedotin is a new, highly effective therapeutic option for these patients. Dose-reduced allogeneic transplant is a therapeutic alternative for patients relapsing after autologous transplant, but induction of a remission is the prerequisite for a successful allogeneic transplant. Brentuximab vedotin has been evaluated as a bridge to allogeneic transplant for patients refractory to conventional treatment. Recent therapeutic advances have improved the prognosis of Hodgkin Lymphoma by prevention or successful treatment of refractory disease. The use of new drugs such as brentuximab vedotin will hopefully further increase the cure rates.

High-quantum efficiency, long-lived luminescing refractory oxides

DOEpatents

Chen, Yok; Gonzalez, Roberto; Summers, Geoffrey P.

1984-01-01

A crystal having a high-quantum efficiency and a long period of luminescence is formed of an oxide selected from the group consisting of magnesium oxide and calcium oxide and possessing a concentration ratio of H.sup.- ions to F centers in the range of about 0.05 to about 10.

Anti-pruritic and anti-inflammatory effects of oxymatrine in a mouse model of allergic contact dermatitis.

PubMed

Xu, Xiaoyun; Xiao, Wei; Zhang, Zhe; Pan, Jianhao; Yan, Yixi; Zhu, Tao; Tang, Dan; Ye, Kaihe; Paranjpe, Manish; Qu, Lintao; Nie, Hong

2018-05-31

Allergic contact dermatitis (ACD) is a highly prevalent inflammatory disease of the skin. As a result of the complex etiology in ACD, therapeutic compounds targeting refractory pruritus in ACD lack efficacy and lead to numerous side effects. In this study, we investigated the anti-pruritic effects of oxymatrine (OMT) and explored its mechanism of action in a mouse model of ACD. 72 male SPF C57BL/6 mice were randomly divided into control group, ACD model group, dexamethasone positive control group (0.08 mg kg -1 ) and 3 OMT groups (80, 40, 20 mg kg -1 ). OMT was administrated by intraperitoneal injection 1 h before video recording on day 10, 24 h after 2nd challenge with SADBE. Cheek skin fold thickness was measured before treatment and after recording. H&E staining was used for pathological observation. RT-qPCR, Immunohistochemistry and LEGENDplexTM assay were used to detect cytokines levels. The population of Treg cells in peripheral blood were detected via flow cytometry. OMT treatment significantly decreases the skin inflammation and scratching bouts. It rescues defects in epidermal keratinization and inflammatory cell infiltration in ACD mice. Administration of OMT significantly reduced levels of IFN-γ, IL-13, IL-17A, TNF-α, IL-22 and mRNA expression of TNF-α and IL-1β. Furthermore, it increased the percentage of Treg cells in peripheral blood of ACD mice. We have demonstrated that OMT exhibits anti-pruritic and anti-inflammatory effects in ACD mice by regulating inflammatory mediators. OMT might emerge as a potential drug for the treatment of pruritus and skin inflammation in the setting of ACD. Copyright © 2018. Published by Elsevier B.V.

Refractory lining system for high wear area of high temperature reaction vessel

DOEpatents

Hubble, David H.; Ulrich, Klaus H.

1998-01-01

A refractory-lined high temperature reaction vessel comprises a refractory ring lining constructed of refractory brick, a cooler, and a heat transfer medium disposed between the refractory ring lining and the cooler. The refractory brick comprises magnesia (MgO) and graphite. The heat transfer medium contacts the refractory brick and a cooling surface of the cooler, and is composed of a material that accommodates relative movement between the refractory brick and the cooler. The brick is manufactured such that the graphite has an orientation providing a high thermal conductivity in the lengthwise direction through the brick that is higher than the thermal conductivity in directions perpendicular to the lengthwise direction. The graphite preferably is flake graphite, in the range of about 10 to 20 wt %, and has a size distribution selected to provide maximum brick density. The reaction vessel may be used for performing a reaction process including the steps of forming a layer of slag on a melt in the vessel, the slag having a softening point temperature range, and forming a protective frozen layer of slag on the interior-facing surface of the refractory lining in at least a portion of a zone where the surface contacts the layer of slag, the protective frozen layer being maintained at or about the softening point of the slag.

Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group.

PubMed

Wierzbowska, Agnieszka; Robak, Tadeusz; Pluta, Agnieszka; Wawrzyniak, Ewa; Cebula, Barbara; Hołowiecki, Jerzy; Kyrcz-Krzemień, Sławomira; Grosicki, Sebastian; Giebel, Sebastian; Skotnicki, Aleksander B; Piatkowska-Jakubas, Beata; Kuliczkowski, Kazimierz; Kiełbiński, Marek; Zawilska, Krystyna; Kłoczko, Janusz; Wrzesień-Kuś, Agata

2008-02-01

Patients with primary refractory AML and with early relapses have unfavorable prognoses and require innovative therapeutic approaches. Purine analogs fludarabine (FA) and cladribine (2-CdA) increase cytotoxic effect of Ara-C in leukemic blasts and inhibit DNA repair mechanisms; therefore its association with Ara-C and mitoxantrone (MIT) results in a synergistic effect. In the current report, we present the final results of multi-center phase II study evaluating the efficacy and toxicity of CLAG-M salvage regimen in poor risk refractory/relapsed AML patients. The induction chemotherapy consisted of 2-CdA 5 mg/m2, Ara-C 2 g/m2, MIT 10 mg/m2, and granulocyte-colony stimulating factor. In the case of PR, a second CLAG-M was administered. Patients in CR received consolidation courses based on high doses of Ara-C and MIT with or without 2-CdA. One hundred and eighteen patients from 11 centers were registered; 78 primary resistant and 40 relapsed. Sixty-six patients (58%) achieved CR after one or two courses of CLAG-M, 49 (35%) were refractory, and 8 (7%) died early. WBC >10 g/L and age >34 yr were factors associated with increased risk of treatment failure. Hematological toxicity was the most prominent toxicity of this regimen. The probability of OS at 4 yr was 14% (95% CI 4-23%). OS was influenced by age, WBC >10 g/L and poor karyotype in both univariate and multivariate analyses. The probability of 4 yr DFS was 30% for all 66 patients in CR (95% CI 11-49%). Poor karyotype was the only factor associated with decreased probability of DFS. We conclude that CLAG-M is a well-tolerated and highly effective salvage regimen in poor risk refractory/relapsed AML.

Impact of ranolazine on clinical outcomes and healthcare resource utilization in patients with refractory angina pectoris.

PubMed

Ling, Hua; Packard, Kathleen A; Burns, Tammy L; Hilleman, Daniel E

2013-12-01

Ranolazine is a novel antianginal medication approved for the treatment of chronic angina. There are only limited data concerning the efficacy of ranolazine in reducing healthcare resource utilization in patients with refractory angina pectoris. The primary objective of this analysis was to evaluate the efficacy and safety of ranolazine in refractory angina pectoris. In addition, the impact of ranolazine on healthcare resource utilization was assessed. Consecutive patients with refractory angina pectoris treated with ranolazine at two cardiology practices in the state of Nebraska were included in this analysis. The Canadian Cardiovascular Society (CCS) angina class and frequency and type of healthcare resource consumption were determined during the 12 months prior to and the 12 months after initiation of ranolazine. A total of 150 pts (64 % men) with a mean age of 66 ± 12 years were included in this analysis. All patients had previously undergone coronary revascularization. Nitrates, β-adrenoceptor antagonists (β-blockers), and calcium antagonists (calcium channel blockers) were being used in 83, 97, and 75 % of patients, respectively. During ranolazine treatment, a significant improvement in CCS angina class was observed, with 23 patients improving by one class and no patient experiencing a deterioration in functional class (p = 0.025). A total of 53 side effects occurred in 28 (19 %) patients receiving ranolazine. Of those patients with side effects, four required dose reduction and seven required drug discontinuation. The frequency of clinic visits and emergency room visits was lower during ranolazine treatment, but the differences in frequency were not significant. The number of patients hospitalized and the number of hospitalizations were significantly lower during ranolazine therapy than in the pre-ranolazine study period (p = 0.002). Ranolazine improved the CCS angina class and reduced hospitalizations over a 12-month follow-up period in a group of patients with difficult-to-treat refractory angina pectoris.

Aflibercept administration in neovascular age-related macular degeneration refractory to previous anti-vascular endothelial growth factor drugs: a critical review and new possible approaches to move forward.

PubMed

Lazzeri, Stefano; Ripandelli, Guido; Sartini, Maria Sole; Parravano, Mariacristina; Varano, Monica; Nardi, Marco; Di Desidero, Teresa; Orlandi, Paola; Bocci, Guido

2015-10-01

The recent introduction of anti-VEGF drugs has widely changed the prognosis of exudative age-related macular degeneration (AMD), even if a variable percentage of patients showed an insufficient response. Aflibercept is a new anti-VEGF drug approved by FDA for the treatment of exudative AMD with a wider binding capacity than either bevacizumab or ranibizumab. Therefore, the purposes were as follows: (i) to report anatomical and functional outcomes of switching from bevacizumab/ranibizumab to aflibercept previously described in the scientific literature, (ii) to hypothesize the possible pathophysiological mechanisms of the resistance and tachyphylaxis to anti-VEGF drugs, and (iii) to suggest possible clinical actions to increase the chances of success for such difficult cases. We reviewed the available scientific literature in Medline, Cochrane database, Current Contents, PubMed, and cross-referencing from identified articles, regarding the treatment of exudative AMD patients refractory to bevacizumab and/or ranibizumab and switched to aflibercept monotherapy. We included in this review all the cases in which the diagnosis of refractory or resistant exudative AMD was properly made, and the results of at least one aflibercept injection were described. We reported the outcomes of 21 papers for a total of 1066 eyes affected by exudative AMD resistant to previous anti-VEGF drug injections and switched to aflibercept. Enrolled reports were divided into two groups: 5 prospective reports and 16 retrospective reports. All the reported papers conclude their analysis, stating that switching from bevacizumab/ranibizumab to aflibercept injections can improve outcomes successfully in refractory neovascular AMD patients. Analysis of the papers reported in this review demonstrates that switching from bevacizumab/ranibizumab to aflibercept injections can improve outcomes successfully in refractory neovascular AMD patients. The mechanism for these effects is not yet completely understood.

Allogeneic stem cell transplantation using lymphoablative rather than myeloablative conditioning regimen for relapsed or refractory lymphomas.

PubMed

Yoon, Jae-Ho; Jeon, Young-Woo; Lee, Sung-Eun; Cho, Byung-Sik; Eom, Ki-Seong; Kim, Yoo-Jin; Lee, Seok; Kim, Hee-Je; Min, Chang-Ki; Lee, Jong-Wook; Min, Woo-Sung; Cho, Seok-Goo

2017-03-01

In relapsed or refractory non-Hodgkin lymphoma (NHL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides graft-versus-lymphoma activity resulting in fewer incidences of relapse. However, therapy-related mortality (TRM) remains an important challenge. We attempted to introduce our reduced-intensity conditioning (RIC) regimen. From 2007 to 2013, we treated 28 relapsed or refractory NHLs with allo-HSCT. All were pre-conditioned with fludarabine [FLU, 180 mg/body surface area (BSA)/6 days] and melphalan (MEL, 70 mg/BSA/1 day); 25 (all but 3) were additionally treated with total body irradiation (TBI, 800 cGy/4Fx/2 days). Peripheral blood stem cells were collected from matched siblings (n = 10) or suitably matched unrelated (n = 18) donors. There were eight diffuse large B-cell lymphomas, seven peripheral T-cell lymphoma not otherwise specified, give lymphoblastic lymphomas, two mantle cell lymphomas, and six various other lymphomas. Of these patients, 10 relapsed after auto-HSCT, 5 relapsed after chemotherapy, and 13 were refractory lymphomas. After allo-HSCT, complete remission was achieved in 22 (78.5%) patients. After a median follow-up of 24.8 months, 3-year overall survival and disease-free survival were 62.4 and 59.2% and the 3-year TRM and relapse incidence were 14.9 and 28.6% respectively. Acute and chronic graft-versus-host diseases (GVHDs) were identified in 17 (≥Grade II in 12 patients) and 18 patients respectively, and the group with chronic GVHD showed favourable survival outcomes. In relapsed or refractory NHL, RIC-allo-HSCT using FLU + MEL + 800 cGy TBI showed favourable survival outcomes with acceptable TRM and relapse incidence. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Clinical Efficacy and Safety of Methotrexate versus Hydroxychloroquine in Preventing Lichen Planopilaris Progress: A Randomized Clinical Trial

PubMed Central

Naeini, Farahnaz Fatemi; Saber, Mina; Asilian, Ali; Hosseini, Sayed Mohsen

2017-01-01

Background: Lichen planopilaris is an inflammatory cicatricial alopecia, and its management is a challenge for dermatologists. We aimed to compare the efficacy of methotrexate and hydroxychloroquine on refractory lichen planopilaris. Methods: In a randomized clinical trial, 29 patients were randomly allocated to receive either 15 mg methotrexate/week or 200 mg hydroxychloroquine twice a day for 6 months. Side effects, symptoms/signs, and laboratory tests were assessed periodically. Lichen Planopilaris Activity Index (LPPAI) was measured before intervention and at 2, 4, and 6 months after. The changes from baseline to the end of the study were analyzed within each group and between the two groups by per-protocol and intention-to-treat analysis. Results: After 2 months, mean (standard deviation [SD]) decrease in LPPAI in methotrexate group was significantly more than that in hydroxychloroquine group (1.68 [1.24] vs. 0.8 [0.71], respectively, P = 0.047). Furthermore, after 6 months, mean (SD) decrease in LPPAI in methotrexate group was significantly higher than that in hydroxychloroquine group (3.3 [2.09] vs. 1.51 [0.91], respectively, P = 0.01). The following symptoms/signs showed significant improvements in frequency and/or severity in methotrexate group after intervention: pruritus (P = 0.007), erythema (P = 0.01), perifollicular erythema (P = 0.01), perifollicular scaling (P = 0.08), spreading (P = 0.001), and follicular keratosis (P = 0.04). In hydroxychloroquine group, only erythema (P = 0.004) showed significant improvement. Conclusions: Methotrexate was more effective than hydroxychloroquine in treating refractory lichen planopilaris. PMID:28584619

Split-course, high-dose palliative pelvic radiotherapy for locally progressive hormone-refractory prostate cancer.

PubMed

Gogna, Nirdosh Kumar; Baxi, Siddhartha; Hickey, Brigid; Baumann, Kathryn; Burmeister, Elizabeth; Holt, Tanya

2012-06-01

Local progression, in patients with hormone-refractory prostate cancer, often causes significant morbidity. Pelvic radiotherapy (RT) provides effective palliation in this setting, with most published studies supporting the use of high-dose regimens. The aim of the present study was to examine the role of split-course hypofractionated RT used at our institution in treating this group of patients. A total of 34 men with locoregionally progressive hormone-refractory prostate cancer, treated with a split course of pelvic RT (45-60 Gy in 18-24 fractions) between 2000 and 2008 were analyzed. The primary endpoints were the response rate and actuarial locoregional progression-free survival. Secondary endpoints included overall survival, compliance, and acute and late toxicity. The median age was 71 years (range, 53-88). Treatment resulted in an overall initial response rate of 91%, a median locoregional progression-free survival of 43 months, and median overall survival of 28 months. Compliance was excellent and no significant late toxicity was reported. The split course pelvic RT described has an acceptable toxicity profile, is effective, and compares well with other high-dose palliative regimens that have been previously reported. Copyright © 2012 Elsevier Inc. All rights reserved.

B-IGEV (bortezomib plus IGEV) versus IGEV before high-dose chemotherapy followed by autologous stem cell transplantation in relapsed or refractory Hodgkin lymphoma: a randomized, phase II trial of the Fondazione Italiana Linfomi (FIL).

PubMed

Balzarotti, Monica; Brusamolino, Ercole; Angelucci, Emanuele; Carella, Angelo Michele; Vitolo, Umberto; Russo, Eleonora; Congiu, Angelagiovanna; Gotti, Manuel; Massidda, Stefania; Botto, Barbara; Annechini, Giorgia; Spina, Michele; Re, Alessandro; Zilioli, Vittorio Ruggero; Merli, Francesco; Salvi, Flavia; Stelitano, Caterina; Bonfichi, Maurizio; Rodari, Marcello; Murru, Roberta; Magagnoli, Massimo; Anastasia, Antonella; Mazza, Rita; Giordano, Laura; Santoro, Armando

2016-10-01

This randomized, multicenter study evaluates the addition of bortezomib (13 mg/m(2)) to IGEV (B-IGEV) in patients with relapsed/refractory Hodgkin Lymphoma (HL). Patients received either four courses of IGEV alone (n = 40) or B-IGEV (n = 40). The primary endpoint was the complete response (CR) proportion, evaluated by FDG-PET, after induction chemotherapy. CR proportion was 39% with B-IGEV and 53% with IGEV. PFS and OS were similar between the two groups (two-year PFS: 58% vs 56%; two-year OS: 93% vs 81%). The PET-negative status after treatment was the only variable favorably influencing both PFS (two-year PFS: 77% vs 40%; p = 0.002) and OS (two-year OS: 100% vs 76%; p < 0.001). Toxicity was overall similar with the two regimens. The addition of bortezomib to IGEV does not improve response in relapsed/refractory HL patients. However, its favorable therapeutic and safety profile, and the prognostic role of pre-transplant PET negativity in patients receiving IGEV-based regimens are confirmed.

The safety and efficacy of noncorticosteroid triple immunosuppressive therapy in the treatment of refractory chronic noninfectious uveitis in childhood.

PubMed

Little, Jessica A; Sen, Ethan S; Strike, Helen; Hinchcliffe, Annie; Guly, Catherine M; Lee, Richard W J; Dick, Andrew D; Ramanan, Athimalaipet V

2014-01-01

To assess the safety and efficacy of noncorticosteroid triple immunosuppressive therapy in the treatment of refractory chronic noninfectious childhood uveitis. Subjects were retrospectively selected from a database. Patients were included if they were diagnosed with chronic, noninfectious uveitis at 16 years of age or under and treated with triple immunosuppressive therapy for at least 6 months (following failure of a combination of 2 immunosuppressants). Patient demographics, diagnoses, duration of uveitis, drug dosages, active joint inflammation, and ophthalmologic data were recorded. Efficacy outcomes for triple therapy were recorded at 6 months. Thirteen patients with bilateral uveitis were included. Using Standardized Uveitis Nomenclature (SUN) criteria, at 6 months only 11 eyes (42%) had a 2-step improvement in anterior chamber cell inflammation (n = 26). In addition, 2 patients required additional oral corticosteroid treatment. There were 4 significant infectious adverse events during a total of 21.9 patient-years (PY) on triple therapy (0.18 events per PY). In this group of children with refractory uveitis, addition of a third immunosuppressive agent did not confer substantial benefit in redressing ocular inflammation and was associated with significant infections in a minority of patients.

R-ICE and Lenalidomide in Treating Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma

ClinicalTrials.gov

2018-06-25

CD20 Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

Spent refractory reuse as a slag conditioning additive in the EAF

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

Bennett, James P.; Kwong, Kyei-Sing; Krabbe, Rick

2000-01-01

Refractories removed from service in EAF applications are typically landfilled. A joint USDOE and Steel Manufacturers Association program involving industrial cooperators is evaluating spent refractory recycling/reuse. A review of current recycling practices and a review of progress towards controlling EAF slag chemistry and properties with the additions of basic spent refractories will be discussed.

Selumetinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; BRAF Gene Mutation; GNA11 Gene Mutation; GNAQ Gene Mutation; Histiocytosis; HRAS Gene Mutation; KRAS Gene Mutation; NF1 Gene Mutation; NRAS Gene Mutation; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Refractory Central Nervous System Neoplasm; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma

Microsaccadic sampling of moving image information provides Drosophila hyperacute vision

PubMed Central

Solanki, Narendra; Rien, Diana; Jaciuch, David; Dongre, Sidhartha Anil; Blanchard, Florence; de Polavieja, Gonzalo G; Hardie, Roger C; Takalo, Jouni

2017-01-01

Small fly eyes should not see fine image details. Because flies exhibit saccadic visual behaviors and their compound eyes have relatively few ommatidia (sampling points), their photoreceptors would be expected to generate blurry and coarse retinal images of the world. Here we demonstrate that Drosophila see the world far better than predicted from the classic theories. By using electrophysiological, optical and behavioral assays, we found that R1-R6 photoreceptors’ encoding capacity in time is maximized to fast high-contrast bursts, which resemble their light input during saccadic behaviors. Whilst over space, R1-R6s resolve moving objects at saccadic speeds beyond the predicted motion-blur-limit. Our results show how refractory phototransduction and rapid photomechanical photoreceptor contractions jointly sharpen retinal images of moving objects in space-time, enabling hyperacute vision, and explain how such microsaccadic information sampling exceeds the compound eyes’ optical limits. These discoveries elucidate how acuity depends upon photoreceptor function and eye movements. PMID:28870284

Characteristics and biodegradability of olive mill wastewaters.

PubMed

Karahan Özgün, Özlem; Pala Özkök, İlke; Kutay, Can; Orhon, Derin

2016-01-01

Olive mill wastewaters (OMWs) are mostly characterized by their high-organic content and complex organic compounds in addition to the phenolic compounds. European olive oil manufacturers have to cope up with the same wastewater treatment problem and the applied conventional treatment technologies for OMW were not proved to be very successful in each case. Olive mills are mostly small and medium-sized installations and OMW is generated during the three-four-month-long manufacturing season. The problem is not only the complex wastewater to be treated but also the scattered positioning of the olive mills, the seasonal wastewater generation and the size of the manufacturing facilities. The aim of the study is to identify the organic content of OMW and to assess the biological and chemical treatability of OMWs, in order to assist the development of integrated chemical-biological treatment schemes for best appropriate techniques implementation. The experimental studies show that separation of the particulate fraction improved the biodegradability or reduced the refractory and inhibitory effects of particulate organics.

Radiation processing of organics and biological materials exposed to ocean world surface conditions.

NASA Astrophysics Data System (ADS)

Hand, K. P.; Carlson, R. W.

2017-12-01

Assessing the habitability of ocean worlds, such as Europa and Enceladus, motivates a search for endogenous carbon compounds that could be indicative of a habitable, or even inhabited, subsurface liquid water environment. We have examined the role of destruction and synthesis of organic compounds via 10 keV electron bombardment of ices generated under temperature and pressure conditions comparable to Europa and Enceladus. Short-chain organics and ammonia, in combination with water, were exposed to Mrad to Grad doses and observed to evolve to a `lost' carbon fraction (CO and CO2) and a `retained' carbon fraction (consisting of a highly refractory `ocean world tholin' populated by highly radiation resistant carbonyl, aldehyde, and nitrile components). The retained fraction is of key importance as this likely represents the observable fraction for future spacecraft investigations. We also irradiated microbial spores (B. pumilis) to approximately 2 Grad and have found persistence of biomolecule fractions derived from proteins and nucleic acids.