Proteome-wide analysis of Anopheles culicifacies mosquito midgut: new insights into the mechanism of refractoriness.

PubMed

Vijay, Sonam; Rawal, Ritu; Kadian, Kavita; Singh, Jagbir; Adak, Tridibesh; Sharma, Arun

2018-05-08

Midgut invasion, a major bottleneck for malaria parasites transmission is considered as a potential target for vector-parasite interaction studies. New intervention strategies are required to explore the midgut proteins and their potential role in refractoriness for malaria control in Anopheles mosquitoes. To better understand the midgut functional proteins of An. culicifacies susceptible and refractory species, proteomic approaches coupled with bioinformatics analysis is an effective means in order to understand the mechanism of refractoriness. In the present study, an integrated in solution- in gel trypsin digestion approach, along with Isobaric tag for relative and absolute quantitation (iTRAQ)-Liquid chromatography/Mass spectrometry (LC/MS/MS) and data mining were performed to identify the proteomic profile and differentially expressed proteins in Anopheles culicifacies susceptible species A and refractory species B. Shot gun proteomics approaches led to the identification of 80 proteins in An. culicifacies susceptible species A and 92 in refractory species B and catalogue was prepared. iTRAQ based proteomic analysis identified 48 differentially expressed proteins from total 130 proteins. Of these, 41 were downregulated and 7 were upregulated in refractory species B in comparison to susceptible species A. We report that the altered midgut proteins identified in naturally refractory mosquitoes are involved in oxidative phosphorylation, antioxidant and proteolysis process that may suggest their role in parasite growth inhibition. Furthermore, real time polymerase chain reaction (PCR) analysis of few proteins indicated higher expression of iTRAQ upregulated protein in refractory species than susceptible species. This study elucidates the first proteome of the midguts of An. culicifacies sibling species that attempts to analyze unique proteogenomic interactions to provide insights for better understanding of the mechanism of refractoriness. Functional implications of these upregulated proteins in refractory species may reflect the phenotypic characteristics of the mosquitoes and will improve our understandings of blood meal digestion process, parasite vector interactions and proteomes of other vectors of human diseases for development of novel vector control strategies.

Gastric Per Oral Endoscopic Myotomy (G-POEM) for the Treatment of Refractory Gastroparesis: Early Experience.

PubMed

Malik, Zubair; Kataria, Rahul; Modayil, Rani; Ehrlich, Adam C; Schey, Ron; Parkman, Henry P; Stavropoulos, Stavros N

2018-02-22

Gastric per oral endoscopic myotomy (G-POEM) of the pylorus is a technique that is recently being used to treat gastroparesis. Our aim was to report our experience in performing G-POEM for refractory gastroparesis of different etiologies and determine symptom improvement. Thirteen patients undergoing G-POEM are reported. Pre- and post-procedure gastric emptying study (GES) and PAGI-SYM for symptom severity were obtained. Patients underwent G-POEM by creating a submucosal tunnel starting in the greater curvature of the distal antrum and extending it to the beginning of the duodenal bulb, followed by a full thickness pyloromyotomy. All 13 gastroparesis patients successfully underwent G-POEM (one diabetic [DGp], four idiopathic [IGp], eight postsurgical [PSGp]). Postsurgical patients included 4 s/p esophagectomy for esophageal cancer, 3 s/p Nissen fundoplication, and 1 s/p esophagectomy for achalasia. There were no procedure-related side effects. Of 11 patients completing follow-up questionnaires, eight were improved subjectively (four patients reported considerably better, four patients somewhat better, one unchanged, and two worse). Individual symptom severity scores tended to improve, particularly vomiting, retching, and loss of appetite. Of six patients that had post-G-POEM GES; GES improved in four, unchanged in one, and worsened in one). G-POEM for treatment of refractory gastroparesis appears to be a feasible and safe technique that can be successfully performed in patients with a variety of etiologies including different types of postsurgical gastroparesis. Our initial experience suggests that the majority of patients report some improvement in symptoms, particularly symptoms of vomiting, retching, and loss of appetite. Further experience is needed to determine the efficacy and safety of G-POEM and predict those who best respond to this treatment.

Antegrade continence enemas improve quality of life in patients with medically-refractory encopresis.

PubMed

Church, Joseph T; Simha, Sidd; Wild, Laurie C; Teitelbaum, Daniel H; Ehrlich, Peter F

2017-05-01

Fecal incontinence is a socially debilitating problem for many children. We hypothesized that in selected patients with medically-refractory encopresis, placement of an appendicostomy or cecostomy tube for administration of antegrade continence enemas (ACE) would improve quality of life (QOL). We reviewed all patients with encopresis who underwent appendicostomy or cecostomy placement from 2003 to 2014 at our institution. We contacted subjects' parents by phone and administered 3 surveys: a survey reflecting current stooling habits, a disease-specific QOL survey, and the PedsQL™ QOL survey. QOL surveys were completed twice by parents, once reflecting pre-operative QOL, then again reflecting current QOL. Pre-procedure and post-procedure scores were compared by paired t-test. Ten patients underwent appendicostomy/cecostomy for encopresis. Eight completed phone surveys. All procedures were performed laparoscopically. All patients experienced fecal soiling pre-operatively, whereas 5/8 surveyed patients (63%) noted complete resolution of soiling post-procedure (p<0.01). General and disease-specific QOL improved from pre-procedure to post-procedure in the following domains: social habits, physical activity, ability to spend the night elsewhere, feeling, and overall QOL (p<0.05). PedsQL™ scores improved significantly in physical functioning, social functioning, and overall functioning (p<0.05). Antegrade continence enemas significantly improve quality of life in patients with medically-refractory encopresis, likely related to resolution of soiling. 4. Copyright © 2017. Published by Elsevier Inc.

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.

Palliative sedation: from the family perspective.

PubMed

Vayne-Bossert, Petra; Zulian, Gilbert B

2013-12-01

Palliative sedation (PS) is a treatment option in case of refractory symptoms at the end of life. The emotional impact on nurses and doctors has been widely studied. We explore the experience of family members during a PS procedure. An anonymous questionnaire was sent to the closest family members (n = 17) of patients who died while receiving palliative sedation. The response rate was 59% (10 of 17). Nine relatives were sufficiently informed about PS. In all, 70% evaluated the chosen moment for initiation of PS as adequate. All the relatives noticed a significant improvement in the refractory symptom with a mean reduction in the estimated suffering of 6.25 points on a visual analog scale. Palliative sedation should be performed in the best possible way for the patient and his family in order to efficiently reduce a refractory symptom.

An Integrated Study on a Novel High Temperature High Entropy Alloy

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

Yang, Shizhong

2016-12-31

This report summarizes our recent works of theoretical modeling, simulation, and experimental validation of the simulation results on the new refractory high entropy alloy (HEA) design and oxide doped refractory HEA research. The simulation of the stability and thermal dynamics simulation on potential thermal stable candidates were performed and related HEA with oxide doped samples were synthesized and characterized. The HEA ab initio density functional theory and molecular dynamics physical property simulation methods and experimental texture validation techniques development, achievements already reached, course work development, students and postdoc training, and future improvement research directions are briefly introduced.

Comparison of Refractory Performance in Black Liquor Gasifiers and a Smelt Test System

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

Peascoe, RA

2001-09-25

Prior laboratory corrosion studies along with experience at the black liquor gasifier in New Bern, North Carolina, clearly demonstrate that serious material problems exist with the gasifier's refractory lining. Mullite-based and alumina-based refractories used at the New Bern facility suffered significant degradation even though they reportedly performed adequately in smaller scale systems. Oak Ridge National Laboratory's involvement in the failure analysis, and the initial exploration of suitable replacement materials, led to the realization that a simple and reliable, complementary method for refractory screening was needed. The development of a laboratory test system and its suitability for simulating the environment ofmore » black liquor gasifiers was undertaken. Identification and characterization of corrosion products were used to evaluate the test system as a rapid screening tool for refractory performance and as a predictor of refractory lifetime. Results from the test systems and pl ants were qualitatively similar.« less

Gastric Electric Stimulation for Refractory Gastroparesis: A Prospective Analysis of 151 Patients at a Single Center.

PubMed

Heckert, Jason; Sankineni, Abhinav; Hughes, William B; Harbison, Sean; Parkman, Henry

2016-01-01

Gastric electric stimulation (GES) is used to treat patients with refractory gastroparesis symptoms. However, the effectiveness of GES in clinical practice and the effect of GES on specific symptoms of gastroparesis are not well delineated. To determine the effectiveness of GES for treatment for refractory symptoms of gastroparesis, the improvement in specific symptoms of gastroparesis, and clinical factors impacting on outcome. Enterra GES was used to treat refractory gastroparesis symptoms. Patients filled out a symptom severity questionnaire (PAGI-SYM) prior to insertion. At each follow-up visit, the patient filled out PAGI-SYM and assessed their therapeutic response using the Clinical Patient Grading Assessment Scale (CPGAS). One hundred and fifty-one patients (120 females) with refractory gastroparesis (72 diabetic, 73 idiopathic, 6 other) underwent GES. Of the 138 with follow-up (1.4 ± 1.0 years), the average CPGAS was 2.4 ± 0.3 (SEM): 104 patients (75 %) improved (CPGAS > 0) and 34 (25 %) did not (CPGAS ≤ 0). Sixty patients (43 %) were at least moderately improved (CPGAS score ≥4). Clinical improvement was seen in both diabetic and idiopathic patients with the CPGAS in diabetic patients (3.5 ± 0.3) higher in idiopathic patients (1.5 ± 0.5; p < 0.05). Symptoms significantly improving the most included nausea, loss of appetite, and early satiety. Vomiting improved in both diabetic and idiopathic patients although the diabetic subgroup experienced a significantly greater reduction in vomiting than the idiopathic subgroup. In this cohort of patients with refractory gastroparesis, GES improved symptoms in 75 % of patients with 43 % being at least moderately improved. Response in diabetics was better than in nondiabetic patients. Nausea, loss of appetite, and early satiety responded the best.

Performance Assessment of Refractory Concrete Used on the Space Shuttle's Launch Pad

NASA Technical Reports Server (NTRS)

Trejo, David; Calle, Luz Marina; Halman, Ceki

2005-01-01

The John F. Kennedy Space Center (KSC) maintains several facilities for launching space vehicles. During recent launches it has been observed that the refractory concrete materials that protect the steel-framed flame duct are breaking away from this base structure and are being projected at high velocities. There is significant concern that these projected pieces can strike the launch complex or space vehicle during the launch, jeopardizing the safety of the mission. A qualification program is in place to evaluate the performance of different refractory concretes and data from these tests have been used to assess the performance of the refractory concretes. However, there is significant variation in the test results, possibly making the existing qualification test program unreliable. This paper will evaluate data from past qualification tests, identify potential key performance indicators for the launch complex, and will recommend a new qualification test program that can be used to better qualify refractory concrete.

Management of pediatric patients with refractory constipation who fail cecostomy.

PubMed

Bonilla, Silvana F; Flores, Alejandro; Jackson, Carl-Christian A; Chwals, Walter J; Orkin, Bruce A

2013-09-01

Antegrade continence enema (ACE) is a recognized therapeutic option in the management of pediatric refractory constipation. Data on the long-term outcome of patients who fail to improve after an ACE-procedure are lacking. To describe the rate of ACE bowel management failure in pediatric refractory constipation, and the management and long term outcome of these patients. Retrospective analysis of a cohort of patients that underwent ACE-procedure and had at least 3-year-follow-up. Detailed analysis of subsequent treatment and outcome of those patients with a poor functional outcome was performed. 76 patients were included. 12 (16%) failed successful bowel management after ACE requiring additional intervention. Mean follow-up was 66.3 (range 35-95 months) after ACE-procedure. Colonic motility studies demonstrated colonic neuropathy in 7 patients (58%); abnormal motility in 4 patients (33%), and abnormal left-sided colonic motility in 1 patient (9%). All 12 patients were ultimately treated surgically. Nine patients (75%) had marked clinical improvement, whereas 3 patients (25%) continued to have poor function issues at long term follow-up. Colonic resection, either segmental or total, led to improvement or resolution of symptoms in the majority of patients who failed cecostomy. However, this is a complex and heterogeneous group and some patients will have continued issues. Copyright © 2013 Elsevier Inc. All rights reserved.

A Deceptively Simple Solution for Refractory Melasma: Glycolic Acid Peels and Hydroquinone at Home

PubMed Central

Oka, Aiko; Osawa, Ema; Koshima, Isao

2017-01-01

Summary: Although various treatment methods for melasma have developed, substantial improvement of the condition is sometimes difficult. We have experientially found that some of refractory melasma caused by daily friction can easily be treated by using a combination of a peeling agent (20% glycolic acid) and a depigmenting agent (5% hydroquinone) twice daily at home. And here, by performing skin biopsies, we revealed the pathological mechanism: hyperkeratosis caused by repeated physical stimulus, which prevents infiltration of topical therapeutic agents, was dramatically reduced by chemical peeling, resulting that the melanin pigments were effectively cleared by topical hydroquinone. PMID:28607861

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.

Spinal cord stimulation for patients with refractory angina and previous coronary surgery.

PubMed

Lapenna, Elisabetta; Rapati, Dino; Cardano, Paola; De Bonis, Michele; Lullo, Francesca; Zangrillo, Alberto; Alfieri, Ottavio

2006-11-01

Refractory angina pectoris is an exceptionally debilitating condition affecting patients who have typically failed multiple percutaneous and surgical revascularizations and optimal medical therapy and who are not amenable for further revascularization procedures. Spinal cord stimulation (SCS) has been adopted in this context at our institution and midterm mortality, anginal status, and quality of life have been evaluated. From 1998 to 2004, 51 patients with refractory class III-IV angina, who were not considered candidates for revascularization procedures, underwent SCS. All patients had already undergone previous surgical revascularization and a median of two percutaneous procedures. Transmyocardial laser revascularization had been previously performed in 8 cases (15.6%). Most of the patients (70.5%) had experienced a myocardial infarction. Mean ejection fraction was 0.42 +/- 0.121, Canadian Cardiovascular Society class 3.5 +/- 0.5, quality of life (Spitzer index) 4.5 +/- 1.2, and the median frequency of weekly angina episodes was 10. There were no SCS implantation-related complications. At follow-up (100% complete, mean 24 +/- 18 months), a significant improvement of anginal symptoms (>50% reduction of weekly anginal episodes) occurred in 45 patients (88.2%). In those patients (Responders), the quality of life improved significantly (6.8 +/- 1.5; p < 0.0001), CCS class decreased to 2 +/- 0.7 (p < 0.0001), and the median frequency of weekly angina episodes to 3 (p < 0.0001). At 3 years, Responders' survival was 91.8 +/- 4.6% and the freedom from cardiac events 72.6 +/- 8.42%. Spinal cord stimulation is a safe and effective procedure in truly no-option patients affected by refractory angina. A midterm sustained improvement of symptoms and quality of life have been documented with a satisfactory 3-year survival rate.

Immediate and long-term clinical outcome after spinal cord stimulation for refractory stable angina pectoris.

PubMed

Di Pede, Francesco; Lanza, Gaetano Antonio; Zuin, Guerrino; Alfieri, Ottavio; Rapati, Massimo; Romanò, Massimo; Circo, Antonio; Cardano, Paola; Bellocci, Fulvio; Santini, Massimo; Maseri, Attilio

2003-04-15

The treatment of patients with angina pectoris refractory to medical therapy and unsuitable for revascularization procedures has yet not been well standardized. Previous retrospective studies and small prospective studies have suggested beneficial effects of spinal cord stimulation (SCS) in these patients. We created a Prospective Italian Registry of SCS to evaluate the short- and long-term clinical outcome of patients who underwent SCS device implantation because of severe refractory angina pectoris. Overall, 104 patients were enrolled in the registry (70 men, aged 68 +/- 17 years), most of whom (83%) had severe coronary artery disease. Average follow-up was 13.2 +/- 8 months. Overall, 17 patients (16%) died, 8 (8%) due to cardiac death. Among clinical variables, only age was found to be significantly associated both with total mortality (p = 0.04) and cardiac mortality (p = 0.02) on Cox regression analysis. A significant improvement of anginal symptoms (> or =50% reduction of weekly anginal episodes, compared with baseline) occurred in 73% of patients, and Canadian Cardiovascular Society angina class improved by > or =1 class in 80% and by > or =2 classes in 42% of patients, with a relevant reduction in the rate of hospital admission and days spent in the hospital because of angina (p <0.0001 for both). No life-threatening or clinically serious complications were observed. The most frequent side effect consisted of superficial infections, either at the site of puncture of electrode insertion or of the abdominal pocket, which occurred in 6 patients. In conclusion, our prospective data point out that SCS can be performed safely and is associated with a sustained improvement of anginal symptoms in a relevant number of patients with refractory stable angina pectoris.

Improving B-cell depletion in systemic lupus erythematosus and rheumatoid arthritis.

PubMed

Mota, Pedro; Reddy, Venkat; Isenberg, David

2017-07-01

Rituximab-based B-cell depletion (BCD) therapy is effective in refractory rheumatoid arthritis (RA) and although used to treat patients with refractory systemic lupus erythematosus (SLE) in routine clinical practice, rituximab failed to meet the primary endpoints in two large randomised controlled trials (RCTs) of non-renal (EXPLORER) and renal (LUNAR) SLE. Areas covered: We review how BCD could be improved to achieve better clinical responses in RA and SLE. Insights into the variability in clinical response to BCD in RA and SLE may help develop new therapeutic strategies. To this end, a literature search was performed using the following terms: rheumatoid arthritis, systemic erythematosus lupus, rituximab and B-cell depletion. Expert commentary: Poor trial design may have, at least partly, contributed to the apparent lack of response to BCD in the two RCTs of patients with SLE. Enhanced B-cell depletion and/or sequential therapy with belimumab may improve clinical response at least in some patients with SLE.

Improved high-temperature silicide coatings

NASA Technical Reports Server (NTRS)

Klopp, W. D.; Stephens, J. R.; Stetson, A. R.; Wimber, R. T.

1969-01-01

Special technique for applying silicide coatings to refractory metal alloys improves their high-temperature protective capability. Refractory metal powders mixed with a baked-out organic binder and sintered in a vacuum produces a porous alloy layer on the surface. Exposing the layer to hot silicon converts it to a silicide.

The neuropsychological outcome of pediatric patients with refractory epilepsy treated with VNS--A 24-month follow-up in Taiwan.

PubMed

Tsai, Jeng-Dau; Chang, Ying-Chao; Lin, Lung-Chang; Hung, Kun-Long

2016-03-01

Multiple studies have reported the benefits of vagus nerve stimulation (VNS) on neuropsychological outcomes. The aim of this study was to investigate how VNS affects cognition and psychosocial adjustment in children with refractory epilepsy (RE), and to determine the efficacy of VNS in a Taiwanese population. We conducted a one-group pretest-posttest study on pediatric patients with RE. The study comprised 19 males and 18 females, all aged <18 years. We recorded seizure frequency at 3, 12, and 24 months after VNS device implantation. Intelligence quotients (IQ) were assessed using the Wechsler Intelligence Scale for Children - IV. The Parental Stress Index (PSI) scores were evaluated by a pediatric psychologist. Vagus nerve stimulation device implantation significantly reduced seizure frequency at 3, 12 and 24 months, especially in young children (<12 years). No significant improvement in IQ test performance was observed, though there were significant improvements in the PSI, especially in young children. Vagus nerve stimulation device implantation does not significantly improve cognition function, but it does significantly reduce seizure frequency and stress in parent-child relationships, especially in young children (<12 years). These findings suggest that VNS should be considered as an alternative therapy for patients proven to have seizures that are medically refractory, especially those younger than 12 years of age. Copyright © 2015 Elsevier Inc. All rights reserved.

Control for monitoring thickness of high temperature refractory

DOEpatents

Caines, M.J.

1982-11-23

This invention teaches an improved monitoring device for detecting the changes in thickness of high-temperature refractory, the device consists of a probe having at least two electrically conductive generally parallel elements separated by a dielectric material. The probe is implanted or embedded directly in the refractory and is elongated to extend in line with the refractory thickness to be measured. Electrical inputs to the conductive elements provide that either or both the electrical conductance or capacitance can be found, so that charges over lapsed time periods can be compared in order to detect changes in the thickness of the refractory.

Evaluation of olivine ceramic refractories for thermal-energy-storage application

NASA Astrophysics Data System (ADS)

Palmour, H., III; Gay, B. M.; Cochran, R. L.

The degree of improvement in thermal and mechanical performance that can be obtained with an olivine thermal storage brick made of domestic materials using advanced processing techniques compared with state-of-the-art as represented by commercial European bricks is discussed. The goals and results of the study are given.

Enhancing Soldier Performance: A Nonlinear Model of Performance to Improve Selection Testing and Training

DTIC Science & Technology

1994-07-01

psychological refractory period 15. Two-flash threshold 16. Critical flicker fusion (CFF) 17. Steady state visually evoked response 18. Auditory brain stem...States of awareness I: Subliminal erceoption relationships to situational awareness (AL-TR-1992-0085). Brooks Air Force BaSe, TX: Armstrong...the signals required different inputs (e.g., visual versus auditory ) (Colley & Beech, 1989). Despite support of this theory from such experiments

Transoral Incisionless Fundoplication (TIF 2.0): A Meta-Analysis of Three Randomized, Controlled Clinical Trials.

PubMed

Gerson, Lauren; Stouch, Bruce; Lobonţiu, Adrian

2018-01-01

The TIF procedure has emerged as an endoscopic treatment for patients with refractory gastro-esophageal reflux disease (GERD). Previous systematic reviews of the TIF procedure conflated findings from studies with modalities that do not reflect the current 2.0 procedure technique or refined data-backed patient selection criteria. A meta-analysis was conducted using data only from randomized studies that assessed the TIF 2.0 procedure compared to a control. The purpose of the meta-analysis was to determine the efficacy and long-term outcomes associated with performance of the TIF 2.0 procedure in patients with chronic long-term refractory GERD on optimized PPI therapy, including esophageal pH, PPI utilization and quality of life. Methods: Three prospective research questions were predicated on the outcomes of the TIF procedure compared to patients who received PPI therapy or sham, concomitant treatment for GERD, and the patient-reported quality of life. Event rates were calculated using the random effect model. Since the time of follow-up post-TIF procedure was variable, analysis was performed to incorporate the time of follow-up for each individual patient at the 3-year time point. Results: Results from this meta-analysis, including data from 233 patients, demonstrated that TIF subjects at 3 years had improved esophageal pH, a decrease in PPI utilization, and improved quality of life. Conclusions: In a meta-analysis of randomized, controlled trials (RCTs), the TIF procedure data for patients with GERD refractory to PPI's produces significant changes, compared with sham or PPI therapy, in esophageal pH, decreased PPI utilization, and improved quality of life. Celsius.

Improved Sand-Compaction Method for Lost-Foam Metal Casting

NASA Technical Reports Server (NTRS)

Bakhtiyarov, Sayavur I.; Overfelt, Ruel A.

2008-01-01

An improved method of filling a molding flask with sand and compacting the sand around a refractory-coated foam mold pattern has been developed for incorporation into the lost-foam metal-casting process. In comparison with the conventional method of sand filling and compaction, this method affords more nearly complete filling of the space around the refractory-coated foam mold pattern and more thorough compaction of the sand. In so doing, this method enables the sand to better support the refractory coat under metallostatic pressure during filling of the mold with molten metal.

An Assessment of Recycled Refractory Material Performance After Two Years of Service in a Carbon Bake Furnace

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

Schubert, N.; Bennett, J.P.; Kwong, K.S.

1999-10-27

Material removed from carbon bake furnaces used to manufacture anodes for the production of aluminum metal has historically been disposed by landfill. This material is composed primarily of 50% alumina refractory. in 1997, Alcoa completed a highly successful program to reuse the spent refractories in castables for carbon bake furnace headwalls and flooring, as roadbed aggregate, and in other internal applications. This program recycled/reused 11,000 metric tons of used refractory material (99% of the material removed from the carbon bake furnace) and saved Alcoa over 3.8 of the 9.6 million dollar projected furnace rebuild costs. As assessment is made ofmore » the performance of the recycled refractory components after two years of service.« less

Refractory of Furnaces to Reduce Environmental Impact

NASA Astrophysics Data System (ADS)

Hanzawa, Shigeru

2011-10-01

The energy load of furnaces used in the manufacturing process of ceramics is quite large. Most of the environmental impact of ceramics manufacturing is due to the CO2 produced from this high energy load. To improve this situation, R&D has focused on furnace systems and techniques of control in order to reduce energy load. Since furnaces are comprised of refractory, consideration of their mechanical and thermal characteristics is important. Herein are described several refractory types which were chosen through comparison of the characteristics which contribute to heat capacity reduction, heat insulating reinforcement and high emissivity, thereby improving thermal radiation heat transfer efficiency to the ceramic articles. One selected refractory material which will reduce the environmental impact of a furnace, chosen considering low heat capacity and high emissivity characteristics, is SiC. In this study, thermal radiation heat transfer efficiency improvement and its effect on ceramic articles in the furnace and oxidation behaviour were investigated at 1700K. A high density SiC refractory, built into the furnace at construction, has relatively high oxidation durability and has the ability to reduce environmental impact-CO2 by 10 percent by decreasing the furnace's energy load. However, new oxidation prevention techniques for SiC will be necessary for long-term use in industrial furnaces, because passive to active oxidation transition behaviour of commercial SiC refractory is coming to close ideal.

Emergency Surgery for Refractory Status Epilepticus.

PubMed

Botre, Abhijeet; Udani, Vrajesh; Desai, Neelu; Jagadish, Spoorthy; Sankhe, Milind

2017-08-15

Management of refractory status epilepticus in children is extremely challenging. Two children with medically refractory status epilepticus, both of whom had lesional pathology on MRI and concordant data on EEG and PET scan. Emergency hemispherotomy performed in both patients. A complete, sustained seizure freedom obtained postoperatively. Emergency surgery is a treatment option in selected cases of drug refractory status epilepticus with lesional pathology and concordant data.

Processing and fabrication of mixed uranium/refractory metal carbide fuels with liquid-phase sintering

NASA Astrophysics Data System (ADS)

Knight, Travis W.; Anghaie, Samim

2002-11-01

Optimization of powder processing techniques were sought for the fabrication of single-phase, solid-solution mixed uranium/refractory metal carbide nuclear fuels - namely (U, Zr, Nb)C. These advanced, ultra-high temperature nuclear fuels have great potential for improved performance over graphite matrix, dispersed fuels tested in the Rover/NERVA program of the 1960s and early 1970s. Hypostoichiometric fuel samples with carbon-to-metal ratios of 0.98, uranium metal mole fractions of 5% and 10%, and porosities less than 5% were fabricated. These qualities should provide for the longest life and highest performance capability for these fuels. Study and optimization of processing methods were necessary to provide the quality assurance of samples for meaningful testing and assessment of performance for nuclear thermal propulsion applications. The processing parameters and benefits of enhanced sintering by uranium carbide liquid-phase sintering were established for the rapid and effective consolidation and formation of a solid-solution mixed carbide nuclear fuel.

Decompressive craniectomy or medical management for refractory intracranial hypertension: an AAST-MIT propensity score analysis.

PubMed

Nirula, Ram; Millar, D; Greene, Tom; McFadden, Molly; Shah, Lubdha; Scalea, Thomas M; Stein, Deborah M; Magnotti, Louis J; Jurkovich, Gregory J; Vercruysse, Gary; Demetriades, Demetrios; Scherer, Lynette A; Peitzman, Andrew; Sperry, Jason; Beauchamp, Kathryn; Bell, Scott; Feiz-Erfan, Iman; O'Neill, Patrick; Coimbra, Raul

2014-04-01

Moderate/severe traumatic brain injury (TBI) management involves minimizing cerebral edema to maintain brain oxygen delivery. While medical therapy (MT) consisting of diuresis, hyperosmolar therapy, ventriculostomy, and barbiturate coma is the standard of care, decompressive craniectomy (DC) for refractory intracranial hypertension (ICH) has gained renewed interest. Since TBI treatment guidelines consider DC a second-tier intervention after MT failure, we sought to determine if early DC (<48 hours) was associated with improved survival in patients with refractory ICH. Eleven Level 1 trauma centers provided clinical data and head computed tomographic scans for patients with a Glasgow Coma Scale (GCS) score of 13 or less and radiographic evidence of TBI excluding deaths within 48 hours. Computed tomographic scans were graded according to the Marshall classification. A propensity score to receive DC (regardless of whether DC was performed) was calculated for each patient based on patient characteristics, physiology, injury severity, GCS, severity of intracranial injury, and treatment center. Patients who actually received a DC were matched to patients with similar propensity scores who received MT for analysis. Outcomes were compared between early (<48 hours of injury) primary or secondary DC and matched controls and then between early primary DC only and matched controls. There were 2,602 patients who met the inclusion criteria ,of whom 264 (10.1%) received DC (either primary or secondary to another cranial procedure) and 109 (5%) had a DC that was primary. Variables associated with performing a DC included sex, race, intracranial pressure monitor placement, in-house trauma attending, traumatic subarachnoid hemorrhage, midline shift, and basal cistern compression. There was no survival benefit with early primary DC compared with the controls (relative risk, 1.07; 95% confidence interval, 0.67-1.73; p = 0.77), and resource use was higher. Early DC does not seem to significantly improve mortality in patients with refractory ICH compared with MT. Neurosurgeons should pause before entertaining this resource-demanding form of therapy. Therapeutic care/management, level III.

Prospective trial of biodegradable stents for refractory benign esophageal strictures after curative treatment of esophageal cancer.

PubMed

Yano, Tomonori; Yoda, Yusuke; Nomura, Shogo; Toyosaki, Kayo; Hasegawa, Hiromi; Ono, Hiroyuki; Tanaka, Masaki; Morimoto, Hiroyuki; Horimatsu, Takahiro; Nonaka, Satoru; Kaneko, Kazuhiro; Sato, Akihiro

2017-09-01

Biodegradable stents are reportedly effective for refractory benign esophageal strictures; however, little is known about their use in patients with refractory stricture after endoscopic submucosal dissection (ESD) or chemoradiotherapy (CRT) for esophageal cancer. This study aimed to evaluate the effectiveness of biodegradable stents for these patients. Patients with refractory benign esophageal stricture with a dysphagia score (DS) of 2 or worse and for whom the passage of a standard size endoscope was not possible were eligible. The primary endpoint was the proportion of those who improved their DSs (% DS improved) at 12 weeks after stent placement, and the secondary endpoints were the proportion of those who improved their DSs at 24 weeks, dysphagia-free survival (DFS), and adverse events. Eighteen patients (men:women, 15:3; median age, 72 years; range, 53-80) were enrolled. Twelve patients improved their DS at 12 weeks (% DS improved, 66.7%; 90% CI, 44.6%-84.4%). Also, 8 of 11 patients (72.7%) after esophagectomy, 4 of 6 patients (66.7%) after ESD, and 3 of 4 patients (75%) after CRT improved at 12 weeks. Three patients who were treated with esophagectomy maintained their DS improvement at 24 weeks (% DS improved, 16.7%; 95% CI, 3.6%-41.4%). The median DFS was 14.1 weeks (95% CI, 13.0-19.0). One patient who had ESD and CRT developed an esophagobronchial fistula 3 months after stent placement. Biodegradable stents are effective and tolerable for refractory benign esophageal strictures after treatment for esophageal cancer; however, long-term efficacy was limited, especially after ESD or CRT. (Clinical trial registration number: UMIN000008054.). Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Carbon transfer from magnesia-graphite ladle refractories to ultra-low carbon steel

NASA Astrophysics Data System (ADS)

Russo, Andrew Arthur

Ultra-low carbon steels are utilized in processes which require maximum ductility. Increases in interstitial carbon lower the ductility of steel; therefore, it is important to examine possible sources of carbon. The refractory ladle lining is one such source. Ladle refractories often contain graphite for its desirable thermal shock and slag corrosion resistance. This graphite is a possible source of carbon increase in ultra-low carbon steels. The goal of this research is to understand and evaluate the mechanisms by which carbon transfers to ultra-low carbon steel from magnesia-graphite ladle refractory. Laboratory dip tests were performed in a vacuum induction furnace under an argon atmosphere to investigate these mechanisms. Commercial ladle refractories with carbon contents between 4-12 wt% were used to investigate the effect of refractory carbon content. Slag-free dip tests and slag-containing dip tests with varying MgO concentrations were performed to investigate the influence of slag. Carbon transfer to the steel was controlled by steel penetrating into the refractory and dissolving carbon in dip tests where no slag was present. The rate limiting step for this mechanism is convective mass transport of carbon into the bulk steel. No detectable carbon transfer occurred in dip tests with 4 and 6 wt%C refractories without slag because no significant steel penetration occurred. Carbon transfer was controlled by the corrosion of refractory by slag in dip tests where slag was present.

Apatinib in refractory radiation-induced brain edema: A case report.

PubMed

Hu, Wei Guo; Weng, Yi Ming; Dong, Yi; Li, Xiang Pan; Song, Qi-Bin

2017-11-01

Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has observed to be effective and safe in refractory radiation-induced brain edema, like Avastin did. Till now, there is no case report after apatinib came in the market. Two patients who received brain radiotherapy developed clinical manifestations of brain edema, including dizziness, headache, limb activity disorder, and so on. Two patients were both diagnosed as refractory radiation-induced brain edema. Two patients received apatinib (500 mg/day) for 2 and 4 weeks. Two patients got symptomatic improvements from apatinib in different degrees. Magnetic resonance imaging after apatinib treatments showed that compared with pre-treatment imaging, the perilesional edema reduced dramatically. However, the toxicity of apatinib was controllable and tolerable. Apatinib can obviously relieve the symptoms of refractory radiation-induced brain edema and improve the quality of life, which offers a new method for refractory radiation-induced brain edema in clinical practices. But that still warrants further investigation in the prospective study.

Treatment of Chronic Cough.

PubMed

Soni, Resha S; Ebersole, Barbara; Jamal, Nausheen

2017-01-01

Objective Chronic cough remains a challenging condition, especially in cases where it persists despite comprehensive medical management. For these particular patients, there appears to be an emerging role for behavior modification therapy. We report a series of patients with refractory chronic cough to assess if there is any benefit of adding behavioral therapy to their treatment regimen. Study Design A case series with planned chart review of patients treated for chronic cough. Setting The review was performed with an outpatient electronic health record system at a tertiary care center. Subjects and Methods The charts of all patients treated for chronic cough by a single laryngologist over a 30-month period were analyzed. Patients' response to treatment and rate of cough improvement were assessed for those with refractory chronic cough who underwent behavior modification therapy. Results Thirty-eight patients with chronic cough were initially treated empirically for the most common causes of cough, of which 32% experienced improvement. Nineteen patients who did not significantly improve with medical management underwent behavior modification therapy with a speech-language pathologist. Of these patients, 84% experienced resolution or marked improvement of their symptoms. Conclusion Behavioral therapy may be underutilized in practice and could lead to improvement of otherwise recalcitrant cough.

Two-Step Oxidation of Refractory Gold Concentrates with Different Microbial Communities.

PubMed

Wang, Guo-Hua; Xie, Jian-Ping; Li, Shou-Peng; Guo, Yu-Jie; Pan, Ying; Wu, Haiyan; Liu, Xin-Xing

2016-11-28

Bio-oxidation is an effective technology for treatment of refractory gold concentrates. However, the unsatisfactory oxidation rate and long residence time, which cause a lower cyanide leaching rate and gold recovery, are key factors that restrict the application of traditional bio-oxidation technology. In this study, the oxidation rate of refractory gold concentrates and the adaption of microorganisms were analyzed to evaluate a newly developed two-step pretreatment process, which includes a high temperature chemical oxidation step and a subsequent bio-oxidation step. The oxidation rate and recovery rate of gold were improved significantly after the two-step process. The results showed that the highest oxidation rate of sulfide sulfur could reach to 99.01 % with an extreme thermophile microbial community when the pulp density was 5%. Accordingly, the recovery rate of gold was elevated to 92.51%. Meanwhile, the results revealed that moderate thermophiles performed better than acidophilic mesophiles and extreme thermophiles, whose oxidation rates declined drastically when the pulp density was increased to 10% and 15%. The oxidation rates of sulfide sulfur with moderate thermophiles were 93.94% and 65.73% when the pulp density was increased to 10% and 15%, respectively. All these results indicated that the two-step pretreatment increased the oxidation rate of refractory gold concentrates and is a potential technology to pretreat the refractory sample. Meanwhile, owing to the sensitivity of the microbial community under different pulp density levels, the optimization of microbial community in bio-oxidation is necessary in industry.

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.

Right prefrontal rTMS treatment for refractory auditory command hallucinations - a neuroSPECT assisted case study.

PubMed

Schreiber, Shaul; Dannon, Pinhas N; Goshen, Elinor; Amiaz, Revital; Zwas, Tzila S; Grunhaus, Leon

2002-11-30

Auditory command hallucinations probably arise from the patient's failure to monitor his/her own 'inner speech', which is connected to activation of speech perception areas of the left cerebral cortex and to various degrees of dysfunction of cortical circuits involved in schizophrenia as supported by functional brain imaging. We hypothesized that rapid transcranial magnetic stimulation (rTMS), by increasing cortical activation of the right prefrontal brain region, would bring about a reduction of the hallucinations. We report our first schizophrenic patient affected with refractory command hallucinations treated with 10 Hz rTMS. Treatment was performed over the right dorsolateral prefrontal cortex, with 1200 magnetic stimulations administered daily for 20 days at 90% motor threshold. Regional cerebral blood flow changes were monitored with neuroSPECT. Clinical evaluation and scores on the Positive and Negative Symptoms Scale and the Brief Psychiatric Rating Scale demonstrated a global improvement in the patient's condition, with no change in the intensity and frequency of the hallucinations. NeuroSPECT performed at intervals during and after treatment indicated a general improvement in cerebral perfusion. We conclude that right prefrontal rTMS may induce a general clinical improvement of schizophrenic brain function, without directly influencing the mechanism involved in auditory command hallucinations.

Characteristics of refractory gastroesophageal reflux disease (GERD) symptoms -is switching proton pump inhibitors based on the patient's CYP2C19 genotype an effective management strategy?

PubMed

Takeuchi, Toshihisa; Oota, Kazuhiro; Harada, Satoshi; Edogawa, Shoko; Kojima, Yuichi; Sanomura, Makoto; Sakaguchi, Masahiro; Hayashi, Katsuyoshi; Hongoh, Yasushi; Itabashi, Tsukasa; Kitae, Hidehiro; Hoshimoto, Masahiro; Takeuchi, Nozomi; Higuchi, Kazuhide

2015-01-01

We investigated factors related to proton pump inhibitor (PPI) -refractory gastroesophageal reflux disease (GERD) symptoms, particularly with respect to acid, the CYP2C19 genotype and psychological aspects. Patients with an Frequency Scale for the Symptoms of GERD (FSSG) score of ≥8 after the initial treatment were switched to therapy with rabeprazole at a dose of 20 mg once daily for eight weeks. We investigated the rate of improvement in PPI-refractory GERD symptoms, background factors, the Hospital Anxiety and Depression Scale (HADS) score and the CYP2C19 genotype. Patients Sixty patients endoscopically diagnosed with reflux esophagitis within the past six months who had received omeprazole at a dose of 20 mg once daily for eight weeks or longer were enrolled. In 71.6% of the patients, the FSSG score decreased to <8 after treatment with omeprazole at a dose of 20 mg once daily for ≥8 weeks, resulting in improvements in their GERD symptoms. Significant factors related to omeprazole-refractory GERD symptoms included a longer disease duration (p=0.0004) and higher HADS score (p=0.01). Among the omeprazole-refractory cases, only 23.5% of the patients showed symptom improvement after switching to rabeprazole. There were no significant differences in the average scores for FSSG (p=0.089) or HADS (p=0.182), before or after the drug change. A total of 92% of the rabeprazole poor responders were homo/hetero extensive metabolizers for the CYP2C19 genotype. Our findings suggest that switching the PPI from omeprazole (20 mg once daily) to rabeprazole (20 mg once daily) is not a significant effective therapeutic strategy for improving PPI-refractory GERD symptoms, taking into consideration possible psychometric factors and patients who require stronger acid suppression than that achieved with a double dose of PPIs for PPI-refractory GERD symptoms.

Refractory Sampling Links Efficiency and Costs of Sensory Encoding to Stimulus Statistics

PubMed Central

Song, Zhuoyi

2014-01-01

Sensory neurons integrate information about the world, adapting their sampling to its changes. However, little is understood mechanistically how this primary encoding process, which ultimately limits perception, depends upon stimulus statistics. Here, we analyze this open question systematically by using intracellular recordings from fly (Drosophila melanogaster and Coenosia attenuata) photoreceptors and corresponding stochastic simulations from biophysically realistic photoreceptor models. Recordings show that photoreceptors can sample more information from naturalistic light intensity time series (NS) than from Gaussian white-noise (GWN), shuffled-NS or Gaussian-1/f stimuli; integrating larger responses with higher signal-to-noise ratio and encoding efficiency to large bursty contrast changes. Simulations reveal how a photoreceptor's information capture depends critically upon the stochastic refractoriness of its 30,000 sampling units (microvilli). In daylight, refractoriness sacrifices sensitivity to enhance intensity changes in neural image representations, with more and faster microvilli improving encoding. But for GWN and other stimuli, which lack longer dark contrasts of real-world intensity changes that reduce microvilli refractoriness, these performance gains are submaximal and energetically costly. These results provide mechanistic reasons why information sampling is more efficient for natural/naturalistic stimulation and novel insight into the operation, design, and evolution of signaling and code in sensory neurons. PMID:24849356

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.

Esophageal Motility and Rikkunshito Treatment for Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease: A Prospective, Uncontrolled, Open-Label Pilot Study Trial.

PubMed

Odaka, Takeo; Yamato, Shigeru; Yokosuka, Osamu

2017-01-01

Only a few reports focused on esophageal motility in patients with proton pump inhibitor (PPI)-refractory nonerosive reflux disease (NERD) and there has been no established strategy for treatment. To clarify the characteristics of esophageal motility in patients with PPI-refractory NERD, we evaluated esophageal function using combined multichannel intraluminal impedance and esophageal manometry (MII-EM). In addition, we evaluated the efficacy of rikkunshito (RKT), which is a gastrointestinal prokinetic agent. Thirty patients with NERD were enrolled and underwent MII-EM. After 8 weeks of RKT (7.5 g/d) treatment, MII-EM was repeated on patients with PPI-refractory NERD. Symptoms were assessed by the Gastrointestinal Symptom Rating Scale. In patients with PPI-refractory NERD, measures of complete bolus transit, peristaltic contractions, and residual pressure of the lower esophageal sphincter during swallowing deviated from the standard values and esophageal clearance was found to be deteriorated. RKT significantly improved the peristaltic contractions ( P < 0.05), the complete bolus transit ( P < 0.01), and the residual pressure of lower esophageal sphincter ( P < 0.05) in these patients. The overall score ( P < 0.01) and the subscale scores of acid reflux syndrome ( P < 0.05), abdominal pain ( P < 0.05), and indigestion syndrome ( P < 0.01) in the Gastrointestinal Symptom Rating Scale were significantly improved by the 8-week RKT treatment. In the pilot study, patients with PPI-refractory NERD had disorders of esophageal and lower esophageal sphincter motility that were improved by RKT. Further studies examining esophageal motor activity of RKT in PPI-refractory NERD are required. University hospital Medical Information Network (UMIN) Clinical Trial Registry identifier: UMIN000003092.

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.

Refractory Materials for Flame Deflector Protection System Corrosion Control: Flame Deflector Protection System Life Cycle Cost Analysis Report

NASA Technical Reports Server (NTRS)

Calle, Luz Marina; Hintze, Paul E.; Parlier, Christopher R.; Coffman, Brekke E.; Kolody, Mark R.; Curran, Jerome P.; Trejo, David; Reinschmidt, Ken; Kim, Hyung-Jin

2009-01-01

A 20-year life cycle cost analysis was performed to compare the operational life cycle cost, processing/turnaround timelines, and operations manpower inspection/repair/refurbishment requirements for corrosion protection of the Kennedy Space Center launch pad flame deflector associated with the existing cast-in-place materials and a newer advanced refractory ceramic material. The analysis compared the estimated costs of(1) continuing to use of the current refractory material without any changes; (2) completely reconstructing the flame trench using the current refractory material; and (3) completely reconstructing the flame trench with a new high-performance refractory material. Cost estimates were based on an analysis of the amount of damage that occurs after each launch and an estimate of the average repair cost. Alternative 3 was found to save $32M compared to alternative 1 and $17M compared to alternative 2 over a 20-year life cycle.

Safety and efficacy of extracorporeal shock wave myocardial revascularization therapy for refractory angina pectoris.

PubMed

Cassar, Andrew; Prasad, Megha; Rodriguez-Porcel, Martin; Reeder, Guy S; Karia, Darshak; DeMaria, Anthony N; Lerman, Amir

2014-03-01

To assess the safety and efficacy of extracorporeal shockwave myocardial revascularization (ESMR) therapy in treating patients with refractory angina pectoris. A single-arm multicenter prospective trial to assess safety and efficacy of the ESMR therapy in patients with refractory angina (class III/IV angina) was performed. Screening exercise treadmill tests and pharmacological single-photon emission computed tomography (SPECT) were performed for all patients to assess exercise capacity and ischemic burden. Patients were treated with 9 sessions of ESMR to ischemic areas over 9 weeks. Efficacy end points were exercise capacity by using treadmill test as well as ischemic burden on pharmacological SPECT at 4 months after the last ESMR treatment. Safety measures included electrocardiography, echocardiography, troponin, creatine kinase, and brain natriuretic peptide testing, and pain questionnaires. Fifteen patients with medically refractory angina and no revascularization options were enrolled. There was a statistically significant mean increase of 122.3±156.9 seconds (38% increase compared with baseline; P=.01) in exercise treadmill time from baseline (319.8±157.2 seconds) to last follow-up after the ESMR treatment (422.1±183.3 seconds). There was no improvement in the summed stress perfusion scores after pharmacologically induced stress SPECT at 4 months after the last ESMR treatment in comparison to that at screening; however, SPECT summed stress score revealed that untreated areas had greater progression in ischemic burden vs treated areas (3.69±6.2 vs 0.31±4.5; P=.03). There was no significant change in the mean summed echo score from baseline to posttreatment (0.4±5.1; P=.70). The ESMR therapy was performed safely without any adverse events in electrocardiography, echocardiography, troponins, creatine kinase, or brain natriuretic peptide. Pain during the ESMR treatment was minimal (a score of 0.5±1.2 to 1.1±1.2 out of 10). In this multicenter feasibility study, ESMR seems to be a safe and efficacious treatment for patients with refractory angina pectoris. However, larger sham-controlled trials will be required to confirm these findings. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Apatinib in refractory radiation-induced brain edema

PubMed Central

Hu, Wei Guo; Weng, Yi Ming; Dong, Yi; Li, Xiang Pan; Song, Qi-Bin

2017-01-01

Abstract Rationale: Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has observed to be effective and safe in refractory radiation-induced brain edema, like Avastin did. Till now, there is no case report after apatinib came in the market. Patient concerns: Two patients who received brain radiotherapy developed clinical manifestations of brain edema, including dizziness, headache, limb activity disorder, and so on. Diagnoses: Two patients were both diagnosed as refractory radiation-induced brain edema. Interventions: Two patients received apatinib (500 mg/day) for 2 and 4 weeks. Outcomes: Two patients got symptomatic improvements from apatinib in different degrees. Magnetic resonance imaging after apatinib treatments showed that compared with pre-treatment imaging, the perilesional edema reduced dramatically. However, the toxicity of apatinib was controllable and tolerable. Lessons: Apatinib can obviously relieve the symptoms of refractory radiation-induced brain edema and improve the quality of life, which offers a new method for refractory radiation-induced brain edema in clinical practices. But that still warrants further investigation in the prospective study. PMID:29145238

Pumped lithium loop test to evaluate advanced refractory metal alloys and simulated nuclear fuel elements

NASA Technical Reports Server (NTRS)

Brandenburf, G. P.; Hoffman, E. E.; Smith, J. P.

1974-01-01

The performance was determined of refractory metal alloys and uranium nitride fuel element specimens in flowing 1900F (1083C) lithium. The results demonstrate the suitability of the selected materials to perform satisfactorily from a chemical compatibility standpoint.

Randomized, double-blind, placebo controlled pilot study of intradetrusor injections of onabotulinumtoxinA for the treatment of refractory overactive bladder persisting following surgical management of benign prostatic hyperplasia.

PubMed

Chughtai, Bilal; Dunphy, Claire; Lee, Richard; Lee, Daniel; Sheth, Seema; Marks, Leonard; Kaplan, Steven A; Te, Alexis E

2014-04-01

We assessed the efficacy of onabotulinumtoxinA (BOTOX, Allergan Inc., Irvine, CA, USA) in patients with refractory overactive bladder (OAB) after treatment for benign prostatic hyperplasia (BPH). This was a two-center, randomized, double-blinded pilot study conducted in patients with OAB secondary to bladder outlet obstruction (BOO), refractory to anticholinergic medication and persistent for greater than 3 months after surgical intervention to relieve obstruction, with an International Prostate Symptom Score (IPSS) > 12. Patients were randomized in 1:1 fashion to either 200 units of onabotulinumtoxinA versus placebo. Fifteen patients received onabotulinumtoxinA versus 13 who received placebo. Follow up was performed at 1 week and then 1, 3, 6, and 9 months. The primary endpoint was reduction in the frequency of micturition per 24 hours by 3-day voiding diary. Secondary endpoints were maximum flow rate (Qmax), post-void residual (PVR), and IPSS scores. Patients receiving onabotulinumtoxinA demonstrated significantly improved quality of life scores at 180 and 270 days after treatment (p = 0.02 and 0.03, respectively) as well as significantly lower International Consultation on Incontinence Questionnaire (ICIQ) scores (p < 0.05). Baseline urinary frequency was 10.5 versus 11.0 voids/day (p = 0.47). Frequency episodes improved from 11 episodes per day to 8 episodes per day in the treatment arm. The placebo arm did not have a decrease in frequency episodes. This response was durable up to 90 days, although this was not statistically significant. IPSS, PVR, and urgency were unchanged postoperatively in both groups. OnabotulinumtoxinA was safe in patients with refractory irritative lower urinary tracts symptoms after surgical treatment of BPH. There were improvements in daily frequency, although the results were not statistically significant. Larger trials are needed to help characterize the utility of onabotulinumtoxinA in the treatment of OAB secondary to BPH.

Successful treatment of refractory seizures with phenobarbital, propofol, and medetomidine following congenital portosystemic shunt ligation in a dog.

PubMed

Heidenreich, Dorothee C; Giordano, Paola; Kirby, Barbara M

2016-11-01

To report a case of refractory seizures following congenital portosystemic shunt (CPSS) ligation that regained normal neurologic and hepatic function with novel treatment. Medical care included constant rate infusions (CRI) of propofol and medetomidine in conjunction with phenobarbital and supportive intensive care. A 2-year-old neutered male Bichon Frise was diagnosed with a single extrahepatic CPSS based on typical clinical signs, laboratory data, abdominal ultrasound, and computed tomographic angiography. Following initiation of standard medical treatment, a complete surgical ligation of the CPSS was performed. Recovery was uneventful until postligation neurologic dysfunction developed 54 hours after surgery. Seizures were controlled with phenobarbital (6 mg/kg IM q 12 h) and propofol CRI (0.3-0.6 mg/kg/min). Attempts to wean the dog from the propofol CRI resulted in recurrence of seizure activity until the addition of medetomidine CRI (0.016 μg/kg/min) 76 hours after initiation of drug-induced coma allowed gradual discontinuation of the propofol CRI. The dog regained full neurologic and hepatic function and had no further seizure activity apart from a small number of seizure episodes 5 and 22 months later. Adjustments in antiepileptic treatment resulted in no further neurologic dysfunction at 27-month follow-up. This report highlights the potential benefit of medetomidine CRI for treatment of postattenuation refractory seizures, which to date have proven impossible to predict and difficult to treat with high mortality rates and persistent neurological deficits in surviving animals. Neuroprotective, drug-sparing, and anti-hypertensive features of medetomidine might improve outcome in postligation refractory seizures. Further investigation and clinical application of medetomidine CRI may improve outcome in this complication of CPSS attenuation. © Veterinary Emergency and Critical Care Society 2015.

Application of high temperature phase change materials for improved efficiency in waste-to-energy plants.

PubMed

Dal Magro, Fabio; Xu, Haoxin; Nardin, Gioacchino; Romagnoli, Alessandro

2018-03-01

This study reports the thermal analysis of a novel thermal energy storage based on high temperature phase change material (PCM) used to improve efficiency in waste-to-energy plants. Current waste-to-energy plants efficiency is limited by the steam generation cycle which is carried out with boilers composed by water-walls (i.e. radiant evaporators), evaporators, economizers and superheaters. Although being well established, this technology is subjected to limitations related with high temperature corrosion and fluctuation in steam production due to the non-homogenous composition of solid waste; this leads to increased maintenance costs and limited plants availability and electrical efficiency. The proposed solution in this paper consists of replacing the typical refractory brick installed in the combustion chamber with a PCM-based refractory brick capable of storing a variable heat flux and to release it on demand as a steady heat flux. By means of this technology it is possible to mitigate steam production fluctuation, to increase temperature of superheated steam over current corrosion limits (450°C) without using coated superheaters and to increase the electrical efficiency beyond 34%. In the current paper a detailed thermo-mechanical analysis has been carried out in order to compare the performance of the PCM-based refractory brick against the traditional alumina refractory bricks. The PCM considered in this paper is aluminium (and its alloys) whereas its container consists of high density ceramics (such as Al 2 O 3 , AlN and Si 3 N 4 ); the different coefficient of linear thermal expansion for the different materials requires a detailed thermo-mechanical analysis to be carried out to ascertain the feasibility of the proposed technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Usefulness of a pleuroperitoneal shunt for treatment of refractory pleural effusion in a patient receiving maintenance hemodialysis.

PubMed

Habuka, Masato; Ito, Toru; Yoshizawa, Yuta; Matsuo, Koji; Murakami, Shuichi; Kondo, Daisuke; Kanazawa, Hiroshi; Narita, Ichiei

2018-03-23

Refractory pleural effusion can be a life-threatening complication in patients receiving maintenance hemodialysis. We report successful treatment of refractory pleural effusion using a Denver® pleuroperitoneal shunt in one such patient. A 54-year-old Japanese man, who had previously undergone left nephrectomy, was admitted urgently to our department because of a high C-reactive protein (CRP) level, right pleural effusion, and right renal abscess. Because antibiotics proved ineffective and his general state was deteriorating, he underwent emergency insertion of a thoracic drainage tube and nephrectomy, and hemodialysis was started. Although his general state improved slowly thereafter, the pleural effusion, which was unilateral and transudative, remained refractory and therefore he needed to be on oxygenation. To control the massive pleural effusion, a pleuroperitoneal shunt was inserted. Thereafter, his respiratory condition became stable without oxygenation and he was discharged. His general condition has since been well. Although pleural effusion is a common complication of maintenance hemodialysis, few reports have documented the use of pleuroperitoneal shunt to control refractory pleural effusion. Pleuroperitoneal shunt has been advocated as an effective and low-morbidity treatment for refractory pleural effusion, and its use for some patients with recurrent pleural effusion has also been reported, without any severe complications. In the present case, pleuroperitoneal shunt improved the patient's quality of life sufficiently to allow him to be discharged home without oxygenation. Pleuroperitoneal shunt should be considered a useful treatment option for hemodialysis patients with refractory pleural effusion.

Perspectives of patients, family caregivers and physicians about the use of opioids for refractory dyspnea in advanced chronic obstructive pulmonary disease

PubMed Central

Rocker, Graeme; Young, Joanne; Donahue, Margaret; Farquhar, Morag; Simpson, Catherine

2012-01-01

Background: A recent national practice guideline recommends the use of opioids for the treatment of refractory dyspnea in patients with advanced chronic obstructive pulmonary disease (COPD). We conducted two qualitative studies to explore the experiences of patients and family caregivers with opioids for refractory COPD-related dyspnea and the perspectives and attitudes of physicians toward opioids in this context. Methods: Patients (n = 8; 5 men, 3 women), their caregivers (n = 12; 5 men, 7 women) and physicians (n = 28, 17 men, 11 women) in Nova Scotia participated in the studies. Semistructured interviews were recorded, transcribed verbatim, coded conceptually and analyzed for emergent themes using interpretive description methodology. Results: Patients reported that opioids provided a sense of calm and relief from severe dyspnea. Family caregivers felt that opioids helped patients to breathe more “normally,” observed improvements in patients’ symptoms of anxiety and depression, and experienced reductions in their own stress. Patients reported substantial improvements in their quality of life. All patients and family caregivers wanted opioid therapy to continue. Most physicians were reluctant to prescribe opioids for refractory dyspnea, describing a lack of related knowledge and experience, and fears related to the potential adverse effects and legal censure. Interpretation: Discrepancies between the positive experiences of patients and family caregivers with opioids and the reluctance of physicians to prescribe opioids for refractory dyspnea constitute an important gap in care. Bridging this gap will require initiatives to improve the uptake of practice guidelines and to increase confidence in prescribing opioids for dyspnea refractory to conventional treatment. PMID:22529167

Perspectives of patients, family caregivers and physicians about the use of opioids for refractory dyspnea in advanced chronic obstructive pulmonary disease.

PubMed

Rocker, Graeme; Young, Joanne; Donahue, Margaret; Farquhar, Morag; Simpson, Catherine

2012-06-12

A recent national practice guideline recommends the use of opioids for the treatment of refractory dyspnea in patients with advanced chronic obstructive pulmonary disease (COPD). We conducted two qualitative studies to explore the experiences of patients and family caregivers with opioids for refractory COPD-related dyspnea and the perspectives and attitudes of physicians toward opioids in this context. Patients (n = 8; 5 men, 3 women), their caregivers (n = 12; 5 men, 7 women) and physicians (n = 28, 17 men, 11 women) in Nova Scotia participated in the studies. Semistructured interviews were recorded, transcribed verbatim, coded conceptually and analyzed for emergent themes using interpretive description methodology. Patients reported that opioids provided a sense of calm and relief from severe dyspnea. Family caregivers felt that opioids helped patients to breathe more "normally," observed improvements in patients' symptoms of anxiety and depression, and experienced reductions in their own stress. Patients reported substantial improvements in their quality of life. All patients and family caregivers wanted opioid therapy to continue. Most physicians were reluctant to prescribe opioids for refractory dyspnea, describing a lack of related knowledge and experience, and fears related to the potential adverse effects and legal censure. Discrepancies between the positive experiences of patients and family caregivers with opioids and the reluctance of physicians to prescribe opioids for refractory dyspnea constitute an important gap in care. Bridging this gap will require initiatives to improve the uptake of practice guidelines and to increase confidence in prescribing opioids for dyspnea refractory to conventional treatment.

Role of Microstructure on the Performance of UHTC's

NASA Technical Reports Server (NTRS)

Johnson, Sylvia M.; Gasch, Matthew J.; Stackpoole, Mairead; Gusman, Mike; Thornton, Jeremy

2009-01-01

UHTCs, because of their refractory nature and high thermal conductivity, are candidates for use on sharp leading edges of hypersonic vehicles. NASA Ames has been investigating the use of UHTCs in the HfB2/SiC family under NASA's Fundamental Aeronautics Program. The goal of this work has been to tailor the microstructure to improve mechanical properties and the performance in reentry conditions, as determined by arcjet testing. This talk discusses results of mechanical evaluation and arcjet testing of various materials with different microstructures, including the incorporation of high-temperature fibers in these materials to improve fracture toughness. Some preliminary information on UHTC composites will also be discussed.

Gastroesophageal Reflux Management with the LINX® System for Gastroesophageal Reflux Disease Following Laparoscopic Sleeve Gastrectomy.

PubMed

Desart, Kenneth; Rossidis, Georgios; Michel, Michael; Lux, Tamara; Ben-David, Kfir

2015-10-01

Laparoscopic sleeve gastrectomy (LSG) has gained significant popularity in the USA, and consequently resulted in patients experiencing new-onset gastroesophageal reflux disease (GERD) following this bariatric procedure. Patients with GERD refractory to medical therapy present a more challenging situation limiting the surgical options to further treat the de novo GERD symptoms since the gastric fundus to perform a fundoplication is no longer an option. The aim of this study is to determine if the LINX® magnetic sphincter augmentation system is a safe and effective option for patients with new gastroesophageal reflux disease following laparoscopic sleeve gastrectomy. This study was conducted at the University Medical Center. This is a retrospective review of seven consecutive patients who had a laparoscopic LINX® magnetic sphincter device placement for patients with refractory gastroesophageal reflux disease after laparoscopic sleeve gastrectomy between July 2014 and April 2015. All patients were noted to have self-reported greatly improved gastroesophageal reflux symptoms 2-4 weeks after their procedure. They were all noted to have statistically significant improved severity and frequency of their reflux, regurgitation, epigastric pain, sensation of fullness, dysphagia, and cough symptoms in their postoperative GERD symptoms compared with their preoperative evaluation. This is the first reported pilot case series, illustrating that the LINX® device is a safe and effective option in patients with de novo refractory gastroesophageal reflux disease after a laparoscopic sleeve gastrectomy despite appropriate weight loss.

Vedolizumab as a rescue therapy for patients with medically refractory Crohn's disease.

PubMed

Crowell, K T; Tinsley, A; Williams, E D; Coates, M D; Bobb, A; Koltun, W A; Messaris, E

2018-04-19

Vedolizumab, a monoclonal antibody resulting in gut-selective anti-inflammatory activity, was approved by the US Food and Drug Administration in 2014 for use in patients with Crohn's disease (CD). The aim of this study was to investigate the efficacy of vedolizumab as a rescue therapy when other medical therapies have failed. A retrospective review was performed on consecutive patients with CD receiving vedolizumab at the Penn State Hershey IBD Center between May 2014 and March 2016. These patients were unresponsive or intolerant to tumour necrosis factor (TNF) antagonist therapy, and previously would have been candidates for surgery. Outcomes included surgical intervention, clinical response and endoscopic improvement. A total of 48 patients with medically refractory CD receiving vedolizumab were included. The median length of follow-up was 69 weeks (range 15-113 weeks). A majority (81%) of patients previously failed at least two TNF antagonists, and 77% had prior surgery for CD. Surgical intervention was required in 21 (44%) patients and 13 (27%) patients required intra-abdominal operations. At the conclusion of the study, 23 (48%) patients reported continued improvement of symptoms, and 22 of 37 (59%) patients undergoing endoscopy showed improvement. Patients with the inflammatory CD phenotype were more likely to improve clinically and avoid surgery. Vedolizumab alone or in combination with immunomodulators or steroids may be used as a rescue therapy in patients with medically refractory CD and may decrease the rate of surgical intervention. Patients with the inflammatory CD phenotype had the best clinical response and decreased need for surgery, suggesting that vedolizumab is most effective in the inflammatory phenotype. Colorectal Disease © 2018 The Association of Coloproctology of Great Britain and Ireland.

Moving Beyond Conventional Clinical Trial End Points in Treatment-refractory Metastatic Colorectal Cancer: A Composite Quality-of-life and Symptom Control End Point.

PubMed

Gong, Jun; Wu, Daniel; Chuang, Jeremy; Tuli, Richard; Simard, John; Hendifar, Andrew

2017-11-01

This review highlights the evidence supporting symptom control and quality-of-life (QOL) measures as predictors of survival in treatment-refractory metastatic colorectal cancer (mCRC) and describes a composite symptom control and QOL end point recently reported in a Phase III trial that may serve as a more reasonable end point of efficacy in this population. A literature search was conducted using MEDLINE to identify clinical studies (including case series and observational, retrospective, and prospective studies) that reported the predictive value of QOL measures for survival in mCRC. The search was limited by the following key words: quality of life, survival, and colorectal cancer. We then performed a second search limited to studies of randomized and Phase III design in mCRC to identify studies that used QOL assessments as their primary end points. A manual search was also performed to include additional studies of potential relevance. There is increasing evidence to support that symptom control and QOL measures are predictors of survival in treatment-refractory mCRC and can serve as an alternative but equally as important end point to survival in this population. A recent large, randomized Phase III trial using a composite primary end point of lean body mass, pain, anorexia, and fatigue reported the feasibility in evaluating benefit in mCRC beyond conventional clinical trial end points. Future studies in treatment-refractory mCRC may be better served by evaluating improvement in symptom control and QOL, which may otherwise serve as the best predictor of survival in last-line treatment settings. Copyright © 2017 Elsevier HS Journals, 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.

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.).

Combination therapy of ethinylestradiol and somatostatin analogue reintroduces objective clinical responses and decreases chromogranin a in patients with androgen ablation refractory prostate cancer.

PubMed

Di Silverio, Franco; Sciarra, Alessandro

2003-11-01

We evaluated whether a combination therapy of ethinylestradiol and somatostatin analogue can reintroduce objective clinical responses in patients with metastatic androgen ablation refractory prostate cancer (PC). Ten patients with stage D3 disease and bone metastases who had progression despite initial responses to combined androgen blockade and in whom antiandrogen withdrawal subsequently failed discontinued combined androgen blockade and received 1 mg ethinylestradiol orally daily and 73.9 mg lanreotide acetate intramuscularly every 4 weeks. Serum prostate specific antigen (PSA), chromogranin A (CgA), Eastern Cooperative Oncology Group performance status and bone pain scores were assessed at regular intervals. Median followup was 18 months (range 10 to 24). Nine of the 10 cases (90%, 95% CI 55.5 to 99.8) had an objective clinical response, defined as a greater than 50% PSA decrease (median 87.1%, range 50.2% to 94.4%). PSA normalization (less than 4 ng/ml) was achieved in 3 cases. All patients reported significant and durable improvement in bone pain (median duration 17.5 months) and performance status (median duration 18 months) without major treatment related side effects. Two patients with disease progression died secondary to PC at 16 and 10 months, respectively. All other patients were without progression. We observed a statistically significant decrease in serum CgA during administration and at the response to therapy (median 38.4%, range 28.6% to 64.9%, (p <0.0001). Interestingly CgA was not increased at relapse. This combination therapy seems to reintroduce an objective clinical response and symptomatic improvement in androgen ablation refractory PC cases.

Cohort study of lumbar percutaneous chemonucleolysis using ethanol gel in sciatica refractory to conservative treatment.

PubMed

Touraine, Sébastien; Damiano, Joël; Tran, Olivia; Laredo, Jean-Denis

2015-11-01

To investigate the efficacy of percutaneous chemonucleolysis using ethanol gel (PCEG) in alleviating radicular pain due to disc herniation after failure of conservative treatment. After failure of conservative treatment, PCEG was performed under fluoroscopic guidance in 42 patients with sciatica >4/10 on a Visual Analog Scale (VAS) for at least 6 weeks and consistent disc herniation on MRI or CT <3 months. The VAS pain score was determined at baseline, then after 1 and 3 months. We assessed the influence of patient-related factors (age, gender, pain duration) and disc herniation-related factors (level, migration pattern, disc herniation-related spinal stenosis) on outcome of PCEG. Mean pain duration was 6.7 months. Pain intensity decreased by 44% and 62.6% after 1 and 3 months, respectively, versus baseline (P = 0.007). A mild improvement was noted by the rheumatologist in 30/42 (71.4%) and 36/42 (85.7%) patients after 1 and 3 months, respectively, and in 31/42 (73.8%) and 33/42 (78.6%) patients by self-evaluation. Patients who failed PCEG were significantly older (49.8 vs. 37.3 years, P = 0.03). None of the other variables studied were significantly associated with pain relief. PCEG may significantly improve disc-related radicular pain refractory to conservative treatment. • Percutaneous chemonucleolysis using ethanol gel (PCEG) is feasible on an outpatient basis. • PCEG improves disc-related radicular pain refractory to conservative treatment. • PCEG is feasible on an outpatient basis. • Failure of PCEG does not interfere with subsequent spinal surgery.

Endocytic pathway mediates refractoriness of insect Bactrocera dorsalis to RNA interference

PubMed Central

Li, Xiaoxue; Dong, Xiaolong; Zou, Cong; Zhang, Hongyu

2015-01-01

RNA interference (RNAi) is a powerful and convenient tool for sequence-specific gene silencing, and it is triggered by double-stranded RNA (dsRNA). RNAi can be easily achieved in many eukaryotes by either injecting or feeding dsRNAs. This mechanism has demonstrated its potential in fundamental research on genetics, medicine and agriculture. However, the possibility that insects might develop refractoriness to RNAi remains unexplored. In this study, we report that the oriental fruit fly, Bactrocera dorsalis, became refractory to RNAi using orally administered dsRNA targeting endogenous genes. Furthermore, refractoriness to RNAi is not gene-specific, and its duration depends on the dsRNA concentration. RNAi blockage requires the endocytic pathway. Fluorescence microscopy indicated that in RNAi refractory flies, dsRNA uptake is blocked. Genes involved in the entry of dsRNAs into cells, including chc, cog3, light and others, are down-regulated in RNAi refractory flies. Increasing the endocytic capacity by improving F-actin polymerization disrupts RNAi refractoriness after both primary and secondary dsRNA exposures. Our results demonstrate that an insect can become refractory to RNAi by preventing the entry of dsRNA into its cells. PMID:25731667

Endocytic pathway mediates refractoriness of insect Bactrocera dorsalis to RNA interference.

PubMed

Li, Xiaoxue; Dong, Xiaolong; Zou, Cong; Zhang, Hongyu

2015-03-03

RNA interference (RNAi) is a powerful and convenient tool for sequence-specific gene silencing, and it is triggered by double-stranded RNA (dsRNA). RNAi can be easily achieved in many eukaryotes by either injecting or feeding dsRNAs. This mechanism has demonstrated its potential in fundamental research on genetics, medicine and agriculture. However, the possibility that insects might develop refractoriness to RNAi remains unexplored. In this study, we report that the oriental fruit fly, Bactrocera dorsalis, became refractory to RNAi using orally administered dsRNA targeting endogenous genes. Furthermore, refractoriness to RNAi is not gene-specific, and its duration depends on the dsRNA concentration. RNAi blockage requires the endocytic pathway. Fluorescence microscopy indicated that in RNAi refractory flies, dsRNA uptake is blocked. Genes involved in the entry of dsRNAs into cells, including chc, cog3, light and others, are down-regulated in RNAi refractory flies. Increasing the endocytic capacity by improving F-actin polymerization disrupts RNAi refractoriness after both primary and secondary dsRNA exposures. Our results demonstrate that an insect can become refractory to RNAi by preventing the entry of dsRNA into its cells.

[Platelet allo-antibodies identification strategies for preventing and managing platelet refractoriness].

PubMed

Basire, A; Picard, C

2014-11-01

Platelet refractoriness is a serious complication for patients receiving recurrent platelet transfusions, which can be explained by non-immune and immune causes. Human Leukocyte Antigens (HLA) allo-immunization, especially against HLA class I, is the major cause for immune platelet refractoriness. To a lesser extent, allo-antibodies against specific Human Platelet Antigen (HPA) are also involved. Pregnancy, transplantation and previous transfusions can lead to allo-immune reaction against platelet antigens. After transfusion, platelet count is decreased by accelerated platelet destruction related to antibodies fixation on incompatible platelet antigens. New laboratory tests for allo-antibodies identification were developed to improve sensibility and specificity, especially with the LUMINEX(®) technology. The good use and interpretation of these antibodies assays can improve strategies for platelet refractoriness prevention and management with a patient adapted response. Compatible platelets units can be selected according to their identity with recipient typing or immune compatibility regarding HLA or HPA antibodies or HLA epitope compatibility. Prospective studies are needed to further confirm the clinical benefit of new allo-antibodies identification methods and consensus strategies for immune platelet refractoriness management. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

LINX®, a novel treatment for patients with refractory asthma complicated by gastroesophageal reflux disease: a case report.

PubMed

Sriratanaviriyakul, Narin; Kivler, Celeste; Vidovszky, Tamas J; Yoneda, Ken Y; Kenyon, Nicholas J; Murin, Susan; Louie, Samuel

2016-05-24

Gastroesophageal reflux disease is one of the most common comorbidities in patients with asthma. Gastroesophageal reflux disease can be linked to difficult-to-control asthma. Current management includes gastric acid suppression therapy and surgical antireflux procedures. The LINX® procedure is a novel surgical treatment for patients with gastroesophageal reflux disease refractory to medical therapy. To the best of our knowledge, we report the first case of successful treatment of refractory asthma secondary to gastroesophageal reflux disease using the LINX® procedure. Our patient was a 22-year-old white woman who met the American Thoracic Society criteria for refractory asthma that had remained poorly controlled for 5 years despite progressive escalation to step 6 treatment as recommended by National Institutes of Health-National Asthma Education and Prevention Program guidelines, including high-dose oral corticosteroids, high-dose inhaled corticosteroid plus long-acting β2-agonist, leukotriene receptor antagonist, and monthly omalizumab. Separate trials with azithromycin therapy and roflumilast did not improve her asthma control, nor did bronchial thermoplasty help. Additional consultations with two other university health systems left the patient with few treatment options for asthma, which included cyclophosphamide. Instead, the patient underwent a LINX® procedure after failure of maximal medical therapy for gastroesophageal reflux disease with the additional aim of improving asthma control. After she underwent LINX® treatment, her asthma improved dramatically and was no longer refractory. She had normal exhaled nitric oxide levels and loss of peripheral eosinophilia after LINX® treatment. Prednisone was discontinued without loss of asthma control. The only immediate adverse effects due to the LINX® procedure were bloating, nausea, and vomiting. LINX® is a viable alternative to the Nissen fundoplication procedure for the treatment of patients with gastroesophageal reflux disease and poorly controlled concomitant refractory asthma.

CAR-T cells and allogeneic hematopoietic stem cell transplantation for relapsed/refractory B-cell acute lymphoblastic leukemia.

PubMed

Liu, Jun; Zhang, Xi; Zhong, Jiang F; Zhang, Cheng

2017-10-01

Relapsed/refractory acute lymphoblastic leukemia (ALL) has a low remission rate after chemotherapy, a high relapse rate and poor long-term survival even when allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed. Chimeric antigen receptors redirected T cells (CAR-T cells) can enhance disease remission with a favorable outcome for relapsed/refractory ALL, though some cases quickly relapsed after CAR-T cell treatment. Thus, treatment with CAR-T cells followed by allo-HSCT may be the best way to treat relapsed/refractory ALL. In this review, we first discuss the different types of CAR-T cells. We then discuss the treatment of relapsed/refractory ALL using only CAR-T cells. Finally, we discuss the use of CAR-T cells, followed by allo-HSCT, for the treatment of relapsed/refractory ALL.

[Application of 1% lauromacrogol in the treatment of facial refractory hemangioma and vascular malformations].

PubMed

Wang, Yin; Zhu, Fei; Ning, Jin-long; Li, Xiao-jing; Liu, Ye

2012-11-01

To investigate the clinical effect of 1% lauromacrogol for the treatment of facial refractory hemangioma and vascular malformation. From Sept 2009 to Nov 2011, 55 patients (20 male, 35 female, 1 month to 30 years) with different types of facial hemangiorwa and vascular malformation about 1.0 cm x (0. 5-5.0) cm x 10.0 cm in size, underwent 1% lauromacrogol intratumor injection therapy. Generally, the injection dose, concentration, frequency were determined by the age of the patients, the volume and depth of the lesion. The dose was limited to 10 mg every time. The injection interval is 14 weeks. After followed up for 3-16 months, 41 cases were cured, 9 cases were greatly improved, and 5 were partially improved. Skin necrosis happened in only 2 cases. Lauromacrogol is safe, simple and effective as a sderosing agent for the treatment of facial refractory hemangioma and vascular malformation. It provides a new and alternative way for the treatment of facial refractory hemangioma and vascular malformation.

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.

Application of vincristine-loaded platelet therapy in three dogs with refractory immune-mediated thrombocytopenia.

PubMed

Park, Hyung-Jin; Kim, Ja-Won; Song, Kun-Ho; Seo, Kyoung-Won

2015-01-01

Three dogs presented with refractory immune-mediated thrombocytopenia (IMT). All patients failed to respond to prednisone, which is considered a mainstay of immunosuppressive therapy. Vincristine-loaded platelets (VLPs), which act selectively on mononuclear phagocytes,were introduced. After the VLPs were transfused, two dogs responded quickly with improved clinical signs while the third dog with recurrent IMT was euthanized due to its deteriorating condition. This case report describes the efficacy of VLP therapy in refractory IMT patients.

HIGH TEMPERATURE REFRACTORY COATING FOR GRAPHITE MOLDS

DOEpatents

Stoddard, S.D.

1958-10-21

An improved foundry mold coating for use with graphite molds used in the casting of uranium is presented. The refractory mold coating serves to keep the molten uranium from contact with graphite of the mold and thus prevents carbon pickup by the molten metal. The refractory coating is made by dry mixing certain specific amounts of aluminum oxide, bentonite, Tennessee ball clay, and a soluble silicate salt. Water is then added to the mixture and the suspension thus formed is applied by spraying onto the mold.

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.

Refractory overactive bladder: Beyond oral anticholinergic therapy

PubMed Central

Glinski, Ronald W.; Siegel, Steven

2007-01-01

Objectives: In this review, we discuss the treatment of refractory overactive bladder (OAB) that has not adequately responded to medication therapy and we propose an appropriate care pathway to the treatment of OAB. We also attempt to address the cost of OAB treatments. Materials and Methods: A selective expert review of the current literature on the subject of refractory OAB using MEDLINE was performed and the data is summarized. We also review our experience in treating refractory OAB. The role and outcomes of various treatment options for refractory OAB are discussed and combined therapy with oral anticholinergics is explored. Emerging remedies including intravesical botulinum toxin injection and pudendal neuromodulation are also reviewed, along with conventional surgical options. Results: In general behavioral therapy, pelvic floor electrical stimulation, magnetic therapy and posterior tibial nerve stimulation (PTNS), have shown symptom decreases in 50-80% of patients with OAB. Depending on the study, combination therapy with oral anticholinergics seems to improve efficacy of behavioral therapy and PTNS in approximately 10-30%. In multicenter, long-term randomized controlled trials, sacral neuromodulation has been shown to improve symptoms of OAB and OAB incontinence in up to 80% of the patients treated. Studies involving emerging therapies such as pudendal serve stimulation suggest that there may be a 15-20% increase in efficacy over sacral neuromodulation, but long-term studies are not yet available. Another emerging therapy, botulinum toxin, is also showing similar success in reducing OAB symptoms in 80-90% of patients. Surgical approaches, such as bladder augmentation, are a last resort in the treatment of OAB and are rarely used at this point unless upper tract damage is a concern and all other treatment options have been exhausted. Conclusion: The vast majority of OAB patients can be managed successfully by behavioral options with or without anticholinergic medications. When those fail, neuromodulation or intravesical botulinum toxin therapies are successful alternatives for most of the remaining group. We encourage practitioners responsible for the care of OAB patients to gain experience with these options. More research is needed to assess the cost-effectiveness of various OAB treatments PMID:19675795

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.

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.

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)

Percutaneous and Endoscopic Adhesiolysis in Managing Low Back and Lower Extremity Pain: A Systematic Review and Meta-analysis.

PubMed

Helm, Standiford; Racz, Gabor B; Gerdesmeyer, Ludger; Justiz, Rafael; Hayek, Salim M; Kaplan, Eugene D; El Terany, Mohamed Ahamed; Knezevic, Nebojsa Nick

2016-02-01

Chronic refractory low back and lower extremity pain is frustrating to treat. Percutaneous adhesiolysis and spinal endoscopy are techniques which can treat chronic refractory low back and lower extremity pain.Percutaneous adhesiolysis is performed by placing the catheter into the tissue plane at the ventrolateral aspect of the foramen so that medications can be injected. Adhesiolysis is used both for pain caused by scarring which is not resistant to catheter placement and other sources of pain, including inflammation in the absence of scarring.Mechanical lysis of scars with a catheter may or may not be necessary for percutaneous adhesiolysis to be effective. Spinal endoscopy allows direct visualization of the epidural space and has the possibility to use laser energy to treat pathology. A systematic review of the effectiveness of percutaneous adhesiolysis and spinal endoscopic adhesiolysis to treat chronic refractory low back and lower extremity pain. To evaluate and update the effectiveness of percutaneous adhesiolysis and spinal endoscopic adhesiolysis to treat chronic refractory low back and lower extremity pain. The available literature on percutaneous adhesiolysis and spinal endoscopic adhesiolysis in treating persistent low back and leg pain was reviewed. The quality of each article used in this analysis was assessed. The level of evidence was classified on a 5-point scale from strong, based upon multiple randomized controlled trials to weak, based upon consensus, as developed by the U.S. Preventive Services Task Force (USPSTF) and modified by ASIPP. Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to September 2015, and manual searches of the bibliographies of known primary and review articles. Pain relief of at least 50% and functional improvement of at least 40% were the primary outcome measures. Short-term efficacy was defined as improvement of 6 months or less; whereas, long-term efficacy was defined more than 6 months. For this systematic review, 45 studies were identified. Of these, for percutaneous adhesiolysis there were 7 randomized controlled trials and 3 observational studies which met the inclusion criteria. For spinal endoscopy, there was one randomized controlled trial and 3 observational studies. Based upon 7 randomized controlled trials showing efficacy, with no negative trials, there is Level I or strong evidence of the efficacy of percutaneous adhesiolysis in the treatment of chronic refractory low back and lower extremity pain. Based upon one high-quality randomized controlled trial, there is Level II to III evidence supporting the use of spinal endoscopy in treating chronic refractory low back and lower extremity pain. The evidence is Level I or strong that percutaneous adhesiolysis is efficacious in the treatment of chronic refractory low back and lower extremity pain. Percutaneous adhesiolysis may be considered as a first-line treatment for chronic refractory low back and lower extremity pain. The evidence is Level II to III that spinal endoscopy is effective in the treatment of chronic refractory low back and lower extremity pain. Spinal pain, chronic low back pain, post lumbar surgery syndrome, epidural scarring, adhesiolysis, endoscopy, radicular pain.

Extracorporeal Membrane Oxygenation for Refractory Cardiac Arrest

PubMed Central

Conrad, Steven A; Rycus, Peter T

2017-01-01

Extracorporeal cardiopulmonary resuscitation (ECPR) is the use of rapid deployment venoarterial (VA) extracorporeal membrane oxygenation to support systemic circulation and vital organ perfusion in patients in refractory cardiac arrest not responding to conventional cardiopulmonary resuscitation (CPR). Although prospective controlled studies are lacking, observational studies suggest improved outcomes compared with conventional CPR when ECPR is instituted within 30–60 min following cardiac arrest. Adult and pediatric patients with witnessed in-hospital and out-of-hospital cardiac arrest and good quality CPR, failure of at least 15 min of conventional resuscitation, and a potentially reversible cause for arrest are candidates. Percutaneous cannulation where feasible is rapid and can be performed by nonsurgeons (emergency physicians, intensivists, cardiologists, and interventional radiologists). Modern extracorporeal systems are easy to prime and manage and are technically easy to manage with proper training and experience. ECPR can be deployed in the emergency department for out-of-hospital arrest or in various inpatient units for in-hospital arrest. ECPR should be considered for patients with refractory cardiac arrest in hospitals with an existing extracorporeal life support program, able to provide rapid deployment of support, and with resources to provide postresuscitation evaluation and management. PMID:28074817

An Approach to Diagnosis and Endovascular Treatment of Refractory Ascites in Liver Transplant: A Pictorial Essay and Clinical Practice Algorithm.

PubMed

Pereira, Keith; Salsamendi, Jason; Fan, Ji

2015-10-01

Recipients of liver transplant are surviving longer as both the surgical procedure and postsurgical care have improved. Despite improvements, serious complications from the procedure remain that significantly affect patient outcome and may result in retransplant. Refractory ascites is one complication, occurring in about 5.6% of transplant recipients. Management of refractory ascites after liver transplant presents a challenge to the multidisciplinary team caring for these patients. We discuss approaches to the diagnosis and treatment of refractory ascites after liver transplant, based on a literature review, with a primary focus on vascular causes. These approaches are illustrated by case examples highlighting our experiences at an academic tertiary medical center. We propose a clinical practice algorithm for optimal endovascular treatment of refractory ascites after liver transplant. The cornerstone of refractory ascites care is diagnosis and treatment of the cause. Vascular causes are not infrequently encountered and, if not treated early, are associated with graft loss and high morbidity and mortality and are major indications for retransplant. For patients with recurrent disease or graft rejection needing large volume paracentesis, the use of a transjugular intrahepatic portosystemic shunt may serve as a bridge to more definitive treatment (retransplant), although it may not be as effective for managing ascites as splenic artery embolization, arguably underused, which is emerging as a potential alternative treatment option. A multidisciplinary strategy for the diagnosis and care of patients with refractory ascites after liver transplant is crucial, with endovascular treatment playing an important role. The aim is for this document to serve as a concise and informative reference to be used by those who may care for patients with this rare yet serious diagnosis.

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.

When all seems lost: management of refractory constipation-Surgery, rectal irrigation, percutaneous endoscopic colostomy, and more.

PubMed

Wilkinson-Smith, V; Bharucha, A E; Emmanuel, A; Knowles, C; Yiannakou, Y; Corsetti, M

2018-05-01

While the pharmacological armamentarium for chronic constipation has expanded over the past few years, a substantial proportion of constipated patients do not respond to these medications. This review summarizes the pharmacological and behavioral options for managing constipation and details the management of refractory constipation. Refractory constipation is defined as an inadequate improvement in constipation symptoms evaluated with an objective scale despite adequate therapy (ie, pharmacological and/or behavioral) that is based on the underlying pathophysiology of constipation. Minimally invasive (ie, rectal irrigation and percutaneous endoscopic colostomy) and surgical therapies are used to manage refractory constipation. This review appraises these options, and in particular, percutaneous endoscopic colostomy, which as detailed by an article in this issue, is a less invasive option for managing refractory constipation than surgery. While these options benefit some patients, the evidence of the risk: benefit profile for these therapies is limited. © 2018 John Wiley & Sons Ltd.

Intramyocardial autologous CD34+ cell therapy for refractory angina: A meta-analysis of randomized controlled trials.

PubMed

Velagapudi, Poonam; Turagam, Mohit; Kolte, Dhaval; Khera, Sahil; Hyder, Omar; Gordon, Paul; Aronow, Herbert D; Leopold, Jane; Abbott, J Dawn

2018-06-05

Previous studies have demonstrated that intramyocardial human CD34+ cells may relieve symptoms and improve clinical outcomes in chronic refractory angina unresponsive to optimal medical therapy or not amenable to revascularization. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the impact of human CD34+ cells compared with placebo in chronic refractory angina. Primary efficacy outcomes in our analysis were angina frequency and exercise time. Primary safety outcomes included major adverse cardiovascular events such as myocardial infarction (MI), stroke and death. Three eligible randomized trials including 269 patients (placebo = 90, CD34+ = 179) were included. Dose of auto-CD34+ cells ranged from 5 × 10 4 to 5 × 10 5  cells/kg. Follow-up ranged from 6 to 24 months. In a pooled analysis, administration of CD34+ cells decreased the risk of all-cause mortality [OR 0.24, 95% CI (0.08-0.73), p = 0.01], reduced angina frequency [mean difference -2.91, 95% CI (-4.57 to -1.25), p = 0.0006] and improved exercise time [mean difference 58.62 s, 95% CI (21.19 to 96.06), p = 0.02] compared with control group. However, there was no significant difference in the risk of myocardial infarction (MI) and stroke between groups. In a meta-analysis, intra-myocardial CD34+ cell therapy was superior to placebo in improving risk of all - cause mortality, angina frequency with an increase in exercise time, without a significant increase in adverse events. This analysis supports further trials of CD34+ cell therapy for ischemic heart disease. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Sodium Nitroprusside Enhanced Cardiopulmonary Resuscitation Improves Short Term Survival in a Porcine Model of Ischemic Refractory Ventricular Fibrillation

PubMed Central

Yannopoulos, Demetris; Bartos, Jason A.; George, Stephen A.; Sideris, George; Voicu, Sebastian; Oestreich, Brett; Matsuura, Timothy; Shekar, Kadambari; Rees, Jennifer; Aufderheide, Tom P.

2017-01-01

Introduction Sodium nitroprusside (SNP) enhanced CPR (SNPeCPR) demonstrates increased vital organ blood flow and survival in multiple porcine models. We developed a new, coronary occlusion/ischemia model of prolonged resuscitation, mimicking the majority of out-of-hospital cardiac arrests presenting with shockable rhythms. Hypothesis SNPeCPR will increase short term (4-hour) survival compared to standard 2015 Advanced Cardiac Life Support (ACLS) guidelines in an ischemic refractory ventricular fibrillation (VF), prolonged CPR model. Methods Sixteen anesthetized pigs had the ostial left anterior descending artery occluded leading to ischemic VF arrest. VF was untreated for 5 minutes. Basic life support was performed for 10 minutes. At minute 10 (EMS arrival), animals received either SNPeCPR (n=8) or standard ACLS (n=8). Defibrillation (200J) occurred every 3 minutes. CPR continued for a total of 45 minutes, then the balloon was deflated simulating revascularization. CPR continued until return of spontaneous circulation (ROSC) or a total of 60 minutes, if unsuccessful. SNPeCPR animals received 2 mg of SNP at minute 10 followed by 1 mg every 5 minutes until ROSC. Standard ACLS animals received 0.5 mg epinephrine every 5 minutes until ROSC. Primary endpoints were ROSC and 4-hour survival. Results All SNPeCPR animals (8/8) achieved sustained ROSC versus 2/8 standard ACLS animals within one hour of resuscitation (p=0.04). The 4-hour survival was significantly improved with SNPeCPR compared to standard ACLS, 7/8 versus 1/8 respectively, p=0.0019. Conclusion SNPeCPR significantly improved ROSC and 4-hour survival compared with standard ACLS CPR in a porcine model of prolonged ischemic, refractory VF cardiac arrest. PMID:27771299

Sodium nitroprusside enhanced cardiopulmonary resuscitation improves short term survival in a porcine model of ischemic refractory ventricular fibrillation.

PubMed

Yannopoulos, Demetris; Bartos, Jason A; George, Stephen A; Sideris, George; Voicu, Sebastian; Oestreich, Brett; Matsuura, Timothy; Shekar, Kadambari; Rees, Jennifer; Aufderheide, Tom P

2017-01-01

Sodium nitroprusside (SNP) enhanced CPR (SNPeCPR) demonstrates increased vital organ blood flow and survival in multiple porcine models. We developed a new, coronary occlusion/ischemia model of prolonged resuscitation, mimicking the majority of out-of-hospital cardiac arrests presenting with shockable rhythms. SNPeCPR will increase short term (4-h) survival compared to standard 2015 Advanced Cardiac Life Support (ACLS) guidelines in an ischemic refractory ventricular fibrillation (VF), prolonged CPR model. Sixteen anesthetized pigs had the ostial left anterior descending artery occluded leading to ischemic VF arrest. VF was untreated for 5min. Basic life support was performed for 10min. At minute 10 (EMS arrival), animals received either SNPeCPR (n=8) or standard ACLS (n=8). Defibrillation (200J) occurred every 3min. CPR continued for a total of 45min, then the balloon was deflated simulating revascularization. CPR continued until return of spontaneous circulation (ROSC) or a total of 60min, if unsuccessful. SNPeCPR animals received 2mg of SNP at minute 10 followed by 1mg every 5min until ROSC. Standard ACLS animals received 0.5mg epinephrine every 5min until ROSC. Primary endpoints were ROSC and 4-h survival. All SNPeCPR animals (8/8) achieved sustained ROSC versus 2/8 standard ACLS animals within one hour of resuscitation (p=0.04). The 4-h survival was significantly improved with SNPeCPR compared to standard ACLS, 7/8 versus 1/8 respectively, p=0.0019. SNPeCPR significantly improved ROSC and 4-h survival compared with standard ACLS CPR in a porcine model of prolonged ischemic, refractory VF cardiac arrest. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Reoperation for refractory epilepsy in childhood: a second chance for selected patients.

PubMed

Ramantani, Georgia; Strobl, Karl; Stathi, Angeliki; Brandt, Armin; Schubert-Bast, Susanne; Wiegand, Gert; Korinthenberg, Rudolf; Stephani, Ulrich; van Velthoven, Vera; Zentner, Josef; Schulze-Bonhage, Andreas; Bast, Thomas

2013-10-01

Reoperations account for >10% in pediatric epilepsy surgery cohorts, and they are especially relevant in young children with catastrophic epilepsy. To determine surgical outcomes and their predictive factors in reoperations for refractory epilepsy in childhood. We retrospectively analyzed presurgical findings, resections, and outcomes of 23 consecutive children who underwent reoperations from 2000 to 2011. Etiology included cortical dysplasia with/without glioneuronal tumor in 19 patients (83%), sole glioneuronal tumor in 2, and tuberous sclerosis and Rasmussen encephalitis in 1 each. The reasons for the failure of the initial surgery were functional considerations in 8 (35%), incorrect delineation of the epileptogenic zone in 8 (35%), and resection not performed as initially planned in 7 (30%) cases. Final procedures included 8 (35%) intralobar, 8 (35%) multilobar resections, and 7 (30%) hemispherotomies. Following reoperations, 14 (61%) patients were seizure free, 6 (26%) showed significant or worthwhile improvement, and 3 (13%) did not respond to surgery. Six of 8 patients who underwent the first resection before the age of 3 years, 6 of 8 whose first resection was limited by functional considerations, and all 7 with hemispherotomy as the final resection achieved seizure freedom after reoperation. Reoperation is particularly beneficial for selected children with refractory epilepsy associated with cortical dysplasia that did not respond to an initial limited and/or early resection but achieved seizure freedom after extensive procedures. When indicated, reoperation should be performed at the youngest possible age to profit from higher functional plasticity in compensating for neurological deficit.

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.

Refractory Pain Management in Amyloid-Associated Peripheral Neuropathy.

PubMed

Warner, Nafisseh S; Watson, James C; Bendel, Markus A; Moeschler, Susan M

2018-05-01

Systemic amyloidosis is a disease that often involves multiple organ systems, including the peripheral nervous system. Patients may present with severe, refractory neuropathic pain; however, the optimal treatment approach for pain for these patients remains unclear. A man with severe, refractory neuropathic pain in his bilateral upper and lower extremities and the trunk secondary to amyloid neuropathy is presented. Multiple medication trials, including neuropathic and opioid agents, produced considerable adverse effects and minimal relief. Scrambler therapy, a novel electrical stimulation modality, was used and was associated with substantial short-term but nonsustained benefit. Spinal cord stimulation was considered, but given his diffuse symptoms, it was deemed a less-than-optimal approach. Ultimately, an intrathecal drug delivery system was placed with infusion of hydromorphone, resulting in substantial pain reduction in all involved areas and with an improved adverse effect profile. This intervention resulted in immense improvement in the patient's quality of life, despite progression of his systemic amyloidosis. Severe pain in the setting of amyloid neuropathy is often difficult to treat. To our knowledge, this represents the first report of Scrambler therapy or an implanted intrathecal drug delivery system used for a patient with refractory amyloidosis-related neuropathic pain, resulting in substantial analgesic benefit and improved quality of life.

Clinical significance of In vivo Cytarabine Induced Gene Expression Signature in AML

PubMed Central

Lamba, Jatinder K.; Pounds, Stanley; Cao, Xueyuan; Crews, Kristine R.; Cogle, Christopher R.; Bhise, Neha; Raimondi, Susana C.; Downing, James R.; Baker, Sharyn D.; Ribeiro, Raul C.; Rubnitz, Jeffrey E.

2016-01-01

Despite initial remission, approximately 60-70% of adult and 30% of pediatric patients experience relapse or refractory AML. Studies so far have identified base line gene expression profiles of pathogenic and prognostic significance in AML, however extent of change in gene expression post-initiation of treatment has not been investigated. Exposure of leukemic cells to chemotherapeutic agents such as cytarabine, a mainstay of AML chemotherapy can trigger adaptive response by influencing leukemic cell transcriptome and hence development of resistance or refractory disease. It is however challenging to perform such a study due to lack of availability of specimens post-drug treatment. In this study our primary objective was to identify in vivo cytarabine induced changes in leukemia cell transcriptome and to evaluate their impact on clinical outcome. Our results highlight genes relevant to cytarabine resistance and support the concept of targeting cytarabine-induced genes as a means of improving response. PMID:26366682

Clinical significance of in vivo cytarabine-induced gene expression signature in AML.

PubMed

Lamba, Jatinder K; Pounds, Stanley; Cao, Xueyuan; Crews, Kristine R; Cogle, Christopher R; Bhise, Neha; Raimondi, Susana C; Downing, James R; Baker, Sharyn D; Ribeiro, Raul C; Rubnitz, Jeffrey E

2016-01-01

Despite initial remission, ∼60-70% of adult and 30% of pediatric patients experience relapse or refractory AML. Studies so far have identified base line gene expression profiles of pathogenic and prognostic significance in AML; however, the extent of change in gene expression post-initiation of treatment has not been investigated. Exposure of leukemic cells to chemotherapeutic agents such as cytarabine, a mainstay of AML chemotherapy, can trigger adaptive response by influencing leukemic cell transcriptome and, hence, development of resistance or refractory disease. It is, however, challenging to perform such a study due to lack of availability of specimens post-drug treatment. The primary objective of this study was to identify in vivo cytarabine-induced changes in leukemia cell transcriptome and to evaluate their impact on clinical outcome. The results highlight genes relevant to cytarabine resistance and support the concept of targeting cytarabine-induced genes as a means of improving response.

[Allogeneic haematopoietic cell transplantation for diffuse large B cell lymphoma: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

PubMed

Gauthier, Jordan; Chantepie, Sylvain; Bouabdallah, Krimo; Jost, Edgar; Nguyen, Stéphanie; Gac, Anne-Claire; Damaj, Gandhi; Duléry, Rémy; Michallet, Mauricette; Delage, Jérémy; Lewalle, Philippe; Morschhauser, Franck; Salles, Gilles; Yakoub-Agha, Ibrahim; Cornillon, Jérôme

2017-12-01

Despite great improvements in the outcome of patients with lymphoma, some may still relapse or present with primary refractory disease. In these situations, allogeneic hematopoietic cell transplantation is a potentially curative option, this is true particularly in the case of after autologous stem cell transplantation if remission can be achieved. Recently, novel agents such as anti-PD1 and BTK inhibitors have started to challenge the use of allogeneic hematopoietic cell transplantation for relapsed or refractory lymphoma. During the 2016 annual workshop of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), we performed a comprehensive review of the literature published in the last 10 years and established guidelines to clarify the indications and transplant modalities in this setting. This section specifically reports on our conclusions regarding diffuse large B cell lymphoma. Copyright © 2017. Published by Elsevier Masson SAS.

Electroconvulsive therapy in Parkinson's disease.

PubMed

Calderón-Fajardo, Humberto; Cervantes-Arriaga, Amin; Llorens-Arenas, Rodrigo; Ramírez-Bermudez, Jesús; Ruiz-Chow, Ángel; Rodríguez-Violante, Mayela

2015-10-01

Purpose To analyze the effectiveness of electroconvulsive therapy for the management of depression and/or psychosis refractory to drug therapy in patients with Parkinson disease.Methods A retrospective study was carried out including patients treated with electroconvulsive therapy during the period between 2002 and 2013. A review of the literature was performed.Results A total of 27 patients were included. In regards to the neuropsychiatric diagnosis, 14 patients had major depression, 12 patients had both psychosis and depression, and only one patient had isolated psychosis. The mean number of electroconvulsive therapy sessions was 12 ± 2.8. After electroconvulsive therapy, all patients showed a statistically significant improvement in the Brief Psychiatric Rating scale (reduction of 52% points) and Hamilton Depression Rating Scale (reduction of 50% points) independent of the presence of psychosis, depression or both.Conclusion Electroconvulsive therapy is effective for the treatment of refractory neuropsychiatric symptoms in Parkinson's disease.

[Epilepsy, cognition and ketogenic diet].

PubMed

Garcia-Penas, J J

2018-03-01

Most individuals with epilepsy will respond to pharmacologic treatment; however, approximately 20-30% will develop medically refractory epilepsy. Cognitive side effects of antiepileptic drugs are common and can negatively affect tolerability, compliance, and long-term retention of the treatment. Ketogenic diet is an effective and well-tolerated treatment for these children with refractory epilepsy without any negative effect on cognition or behavior. To review the current state of experimental and clinical data concerning the neuroprotective and cognitive effects of the ketogenic diet in both humans and animals. In different animal models, with or without epilepsy, the ketogenic diet seems to have neuroprotective and mood-stabilizing effects. In the observational studies in pediatric epilepsy, improvements during treatment with the ketogenic diet are reported in behavior and cognitive function, particularly with respect to attention, alertness, activity level, socialization, and sleep quality. One randomized controlled trial in patients with pediatric refractory epilepsy showed a mood and cognitive activation during ketogenic diet treatment. Ketogenic diet shows a positive impact on behavioral and cognitive functioning in children and adolescents with refractory epilepsy. More specifically, an improvement is observed in mood, sustained attention, and social interaction.

Remission induction using alemtuzumab can permit chemotherapy-refractory chronic lymphocytic leukemia (CLL) patients to undergo allogeneic stem cell transplantation.

PubMed

Knauf, Wolfgang; Rieger, Kathrin; Blau, Wolfgang; Hegenbart, Ute; Von Gruenhagen, Ulrich; Niederwieser, Dietger; Thiel, Eckhard

2004-12-01

The outcome of allogeneic stem cell transplantation depends upon the disease status before transplantation. Patients with refractory disease are at high risk for relapse. To improve the curative potential of the transplant procedure, we treated 3 chemotherapy-refractory CLL patients with alemtuzumab before allogeneic stem cell transplantation. Prior to therapy, all patients suffered from B-symptoms, and had massive adenopathy, splenomegaly, thrombocytopenia, and anemia; two patients had hepatomegaly. Alemtuzumab greatly reduced tumor mass in blood and bone marrow, B-symptoms resolved, and organomegaly improved. Two patients became blood product independent. All patients proceeded to transplantation after conditioning with TBI 2 Gy (n=1) or Treosulfan (n=2) in combination with Fludarabine either from an HLA-matched sibling (n=2) or from an HLA-matched unrelated donor (n=1). All patients engrafted, and are alive and well. Two patients reached complete remission (CR); one patient attained stable partial remission (PR). These heavily pre-treated refractory patients gained substantial clinical benefit from alemtuzumab, and received successful allografts.

TIPSS Procedure in the Treatment of a Single Patient After Recent Heart Transplantation Because of Refractory Ascites Due to Cardiac Cirrhosis

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

Fava, Mario; Meneses, Luis, E-mail: lmeneseq@gmail.com; Loyola, Soledad

2008-07-15

We present the case of a female patient with arrhythmogenic dysplasia of the right ventricle who evolved to refractory heart failure, ascites, and peripheral edema. As a result, heart transplantation was performed. Subsequently, refractory ascites impaired the patient's respiratory function, resulting in prolonged mechanical ventilation. She was successfully treated with transjugular intrahepatic portosystemic shunt (TIPSS) placement, which allowed satisfactory weaning of ventilatory support.

Detection of Active Epstein-Barr Virus Infection in Duodenal Mucosa of Patients With Refractory Celiac Disease.

PubMed

Perfetti, Vittorio; Baldanti, Fausto; Lenti, Marco Vincenzo; Vanoli, Alessandro; Biagi, Federico; Gatti, Marta; Riboni, Roberta; Dallera, Elena; Paulli, Marco; Pedrazzoli, Paolo; Corazza, Gino Roberto

2016-08-01

Refractory celiac disease is characterized by mucosal damage in patients with celiac disease despite a gluten-free diet. Little is known about the mechanisms that cause persistent intestinal inflammation in these patients. We performed a case-control study of 17 consecutive patients diagnosed with refractory celiac disease from 2001 through 2014 (median age, 51 y; 10 women) and 24 patients with uncomplicated celiac disease (controls) to determine whether refractory disease is associated with infection by lymphotropic oncogenic viruses. We performed real-time PCR analyses of duodenal biopsy samples from all patients to detect Epstein-Barr virus (EBV), human herpesvirus-8, and human T-cell lymphotropic virus-I, -II, or -III. We used in situ hybridization and immunohistochemical analyses to identify infected cells and viral proteins. We did not detect human herpesvirus-8 or human T-cell lymphotropic viruses in any of the biopsy specimens. However, 12 of 17 (70.5%) biopsy specimens from patients with refractory celiac disease were positive for EBV, compared with 4 of 24 (16.6%) biopsy specimens from controls (P < .001). EBV was detected in inflammatory cells and enterocytes. An analysis of latency- and replication-associated proteins confirmed active infection. Further studies are needed to determine whether EBV infection contributes to the pathogenesis of refractory celiac disease and enteropathy-associated T-cell lymphoma. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Nationwide survey on the use of eltrombopag in patients with severe aplastic anemia: a report on behalf of the French Reference Center for Aplastic Anemia.

PubMed

Lengline, Etienne; Drenou, Bernard; Peterlin, Pierre; Tournilhac, Olivier; Abraham, Julie; Berceanu, Ana; Dupriez, Brigitte; Guillerm, Gaelle; Raffoux, Emmanuel; de Fontbrune, Flore Sicre; Ades, Lionel; Balsat, Marie; Chaoui, Driss; Coppo, Paul; Corm, Selim; Leblanc, Thierry; Maillard, Natacha; Terriou, Louis; Socié, Gerard; de Latour, Regis Peffault

2018-02-01

Few therapeutic options are available for patients with aplastic anemia who are ineligible for transplantation or refractory to immunosuppressive therapy. Eltrombopag was recently shown to produce trilineage responses in refractory patients. However, the effects of real-life use of this drug remain unknown. This retrospective study (2012-2016) was conducted by the French Reference Center for Aplastic Anemia on patients with relapsed/refractory aplastic anemia, and patients ineligible for antithymocyte globulin or transplantation, who received eltrombopag for at least 2 months. Forty-six patients with aplastic anemia were given eltrombopag without prior antithymocyte globulin treatment (n=11) or after antithymocyte globulin administration (n=35) in a relapsed/refractory setting. Eltrombopag (median daily dose 150 mg) was introduced 17 months (range, 8-50) after the diagnosis of aplastic anemia. At last followup, 49% were still receiving treatment, 9% had stopped due to a robust response, 2% due to toxicity and 40% due to eltrombopag failure. Before eltrombopag treatment, all patients received regular transfusions. The overall rates of red blood cell and platelet transfusion independence were 7%, 33%, 46% and 46% at 1, 3, 6 months and last follow-up. Responses were slower to develop in antithymocyte treatment-naïve patients. In patients achieving transfusion independence, hemoglobin concentration and platelet counts improved by 3 g/dL (interquartile range, 1.4-4.5) and 42×10 9 /L (interquartile range, 11-100), respectively. Response in at least one lineage (according to National Institutes of Health criteria) was observed in 64% of antithymocyte treatment-naïve and 74% of relapsed/refractory patients, while trilineage improvement was observed in 27% and 34%, respectively. We found high rates of hematologic improvement and transfusion independence in refractory aplastic anemia patients but also in patients ineligible for antithymocyte globulin receiving first-line treatment. In conclusion, elderly patients unfit for antithymocyte globulin therapy may benefit from eltrombopag. Copyright© 2018 Ferrata Storti Foundation.

Refractory lining system for high wear area of high temperature reaction vessel

DOEpatents

Hubble, D.H.; Ulrich, K.H.

1998-04-21

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. 10 figs.

Refractory lining system for high wear area of high temperature reaction vessel

DOEpatents

Hubble, D.H.; Ulrich, K.H.

1998-09-22

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. 10 figs.

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.

Brentuximab vedotin (SGN-35) in patients with transplant-naive relapsed/refractory Hodgkin lymphoma.

PubMed

Sasse, Stephanie; Rothe, Achim; Goergen, Helen; Eichenauer, Dennis A; Lohri, Andreas; Kreher, Stephan; Jäger, Ulrich; Bangard, Christopher; Kuhnert, Georg; Böll, Boris; von Tresckow, Bastian; Engert, Andreas

2013-10-01

Only limited data are available on the role of brentuximab vedotin (SGN-35) in transplant-naive relapsed or refractory patients with Hodgkin lymphoma (HL). We thus retrospectively analyzed 14 patients with primary refractory or relapsed HL who were treated with brentuximab vedotin as single agent in a named patient program, who had not received prior high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) due to refractory disease (n = 9), comorbidity (n = 4) and unknown reasons (n = 1). Brentuximab vedotin resulted in an overall response rate of 71% (10/14) with five complete responses (CRs). Five of those patients with refractory disease and four patients with relevant comorbidity responded. Consolidating ASCT (n = 4) or allogeneic SCT (n = 1) was performed in five patients. Median progression-free survival (PFS) was 9 months and the median overall survival (OS) was not reached. These data indicate the therapeutic efficacy of brentuximab vedotin in chemotherapy-refractory transplant-naive patients with HL.

Corpus cavernosum abscess after Winter procedure performance

PubMed Central

Paladino, Joao Roberto; Nascimento, Fabio Jose; Gromatsky, Celso; Pompeo, Antonio Carlos Lima

2014-01-01

A 23-year-old male patient with sickle-cell disease reported his third episode of priapism complicated by the presence of a corpus cavernosum abscess after the performance of a Winter procedure 20 days prior to his presentation. While in hospital for 11 days, two penile needle aspirations and three surgical drainages were performed with associated antibiotic therapy. He evolved with erectile dysfunction refractory to drug therapy and his infectious condition improved. An early penile prosthesis implantation followed after the use of a vacuum pump in an attempt to decrease the fibrotic process of the corpora cavernosa. Final results were positive. PMID:24515231

Extracorporeal shockwave myocardial revascularization improves clinical symptoms and left ventricular function in patients with refractory angina.

PubMed

Zuozienė, Gitana; Laucevičius, Aleksandras; Leibowitz, David

2012-01-01

Medical therapy for refractory angina is limited and the prognosis is poor. Experimental data suggest that the use of extracorporeal shockwave myocardial revascularization (ESMR) can contribute to angiogenesis and improve symptoms of angina and left ventricular (LV) function. The objective of this study was to examine the effects of ESMR on clinical symptoms as well as LV function as assessed by cardiac MRI in patients with refractory angina. Patients with Canadian Cardiovascular Society (CCS) class III-IV angina despite medical therapy and ischemia documented on thallium or echo-dobutamine were eligible for the study. ESMR therapy was applied with a commercially available cardiac shockwave generator system under echocardiographic guidance. LV function was assessed before and 6 months after therapy by cardiac MRI. Twenty patients (four women, 16 men; mean age 64 years, range 45-83) were included in the study. The CCS class after treatment improved in all patients (16 patients angina pectoris CCS from III to II and four patients from IV to III). The use of sublingual nitroglycerin was significantly reduced as well. There was a significant improvement in LV ejection fraction as assessed by blinded MRI following therapy in the overall population (51 vs. 59%, P<0.05). This study demonstrates the potential efficacy of ESMR for the treatment of refractory angina pectoris. The patients showed both a significant clinical response as well as improved LV ejection fraction on serial MRI imaging. Larger studies are needed to adequately define the clinical utility of this novel therapy.

Magnetic Resonance-Guided Focused Ultrasound Neurosurgery for Essential Tremor: A Health Technology Assessment

PubMed Central

Schaink, Alexis; Li, Chunmei; Gajic-Veljanoski, Olga; Wells, David; Higgins, Caroline

2018-01-01

Background The standard treatment option for medication-refractory essential tremor is invasive neurosurgery. A new, noninvasive alternative is magnetic resonance-guided focused ultrasound (MRgFUS) neurosurgery. We aimed to determine the effectiveness, safety, and cost-effectiveness of MRgFUS neurosurgery for the treatment of moderate to severe, medication-refractory essential tremor in Ontario. We also spoke with people with essential tremor to gain an understanding of their experiences and thoughts regarding treatment options, including MRgFUS neurosurgery. Methods We performed a systematic review of the clinical literature published up to April 11, 2017, that examined MRgFUS neurosurgery alone or compared with other interventions for the treatment of moderate to severe, medication-refractory essential tremor. We assessed the risk of bias of each study and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic review of the economic literature and created Markov cohort models to assess the cost-effectiveness of MRgFUS neurosurgery compared with other treatment options, including no surgery. We also estimated the budget impact of publicly funding MRgFUS neurosurgery in Ontario for the next 5 years. To contextualize the potential value of MRgFUS neurosurgery as a treatment option for essential tremor, we spoke with people with essential tremor and their families. Results Nine studies met our inclusion criteria for the clinical evidence review. In noncomparative studies, MRgFUS neurosurgery was found to significantly improve tremor severity and quality of life and to significantly reduce functional disability (GRADE: very low). It was also found to be significantly more effective than a sham procedure (GRADE: high). We found no significant difference in improvements in tremor severity, functional disability, or quality of life between MRgFUS neurosurgery and deep brain stimulation (GRADE: very low). We found no significant difference in improvement in tremor severity compared with radiofrequency thalamotomy (GRADE: low). MRgFUS neurosurgery has a favourable safety profile. We estimated that MRgFUS neurosurgery has a mean cost of $23,507 and a mean quality-adjusted survival of 3.69 quality-adjusted life-years (QALYs). We also estimated that the mean costs and QALYs of radiofrequency thalamotomy and deep brain stimulation are $14,978 and 3.61 QALYs, and $57,535 and 3.94 QALYs, respectively. For people ineligible for invasive neurosurgery, we estimated the incremental cost-effectiveness ratio (ICER) of MRgFUS neurosurgery compared with no surgery as $43,075 per QALY gained. In people eligible for invasive neurosurgery, the ICER of MRgFUS neurosurgery compared with radiofrequency thalamotomy is $109,795 per QALY gained; when deep brain stimulation is compared with MRgFUS neurosurgery, the ICER is $134,259 per QALY gained. Of note however, radiofrequency thalamotomy is performed very infrequently in Ontario. We also estimated that the budget impact of publicly funding MRgFUS neurosurgery in Ontario at the current case load (i.e., 48 cases/year) would be about $1 million per year for the next 5 years. People with essential tremor who had undergone MRgFUS neurosurgery reported positive experiences with the procedure. The tremor reduction they experienced improved their ability to perform activities of daily living and improved their quality of life. Conclusions MRgFUS neurosurgery is an effective and generally safe treatment option for moderate to severe, medication-refractory essential tremor. It provides a treatment option for people ineligible for invasive neurosurgery and offers a noninvasive option for all people considering neurosurgery. For people ineligible for invasive neurosurgery, MRgFUS neurosurgery is cost-effective compared with no surgery. In people eligible for invasive neurosurgery, MRgFUS neurosurgery may be one of several reasonable options. Publicly funding MRgFUS neurosurgery for the treatment of moderate to severe, medication-refractory essential tremor in Ontario at the current case load would have a net budget impact of about $1 million per year for the next 5 years. People with essential tremor who had undergone MRgFUS neurosurgery reported positive experiences. They liked that it was a noninvasive procedure and reported a substantial reduction in tremor that resulted in an improvement in their quality of life. PMID:29805721

When myasthenia gravis is deemed refractory: clinical signposts and treatment strategies

PubMed Central

Mantegazza, Renato; Antozzi, Carlo

2018-01-01

The prognosis for patients with myasthenia gravis (MG) has improved significantly over the past half century, including substantial reductions in mortality and morbidity. However, approximately 10% of patients fails to respond adequately to current therapies and are considered treatment refractory, or treatment intolerant, and up to 80% have disease that fails to achieve complete stable remission. Although patients with autoantibodies to muscle-specific tyrosine kinase (anti-MuSK positive) are more likely to become treatment refractory than those with autoantibodies to the acetylcholine receptor (anti-AChR positive), each of these serotypes is substantially represented in the refractory MG population. Other risk factors for becoming treatment refractory include history of thymoma or thymectomy and female sex. A modified treatment algorithm for MG is proposed: patients who have disease that fails to respond to the stepwise approach to therapy, are treatment intolerant, or who require chronic rescue measures despite ongoing therapy, should be considered treatment refractory and emerging therapies should be considered. Three emerging monoclonal antibody-based therapies are discussed: the anti-B-cell agent rituximab; the terminal complement activation inhibitor eculizumab; and belimumab, which targets B-cell activating factor. Increased understanding of molecular pathophysiology and accurate antibody subtyping in MG should lead to the use of new therapeutic agents and successful management of treatment-refractory patients. PMID:29403543

Feasibility and safety of placement of a newly designed, fully covered self-expandable metal stent for refractory benign pancreatic ductal strictures: a pilot study (with video).

PubMed

Park, Do Hyun; Kim, Myung-Hwan; Moon, Sung-Hoon; Lee, Sang Soo; Seo, Dong-Wan; Lee, Sung-Koo

2008-12-01

Painful chronic pancreatitis with main pancreatic ductal strictures is usually managed with endotherapy with a plastic stent. To date, the role of placement of metallic stents, especially uncovered ones in benign pancreatic ductal stricture, has been unsatisfactory as a result of stent dysfunction related to mucosal hyperplasia. We explored the feasibility and safety of temporary placement of a newly designed, fully covered self-expandable metal stent (FCSEMS) in painful chronic pancreatitis and refractory benign pancreatic ductal strictures. A prospective pilot and feasibility study. A tertiary academic center. Thirteen patients with chronic painful pancreatitis of alcoholic (8) or idiopathic (5) etiology. ERCP with temporary FCSEMS placement (2 months). Endoscopic removal of FCSEMSs was performed with a snare or rat-tooth forceps. End points were feasibility, safety, and morbidity. Successful FCSEMS placement was performed in all enrolled patients. After immediate placement of FCSEMS, 2 patients had mild acute pancreatitis related mainly to the stricture dilation procedure (Soehendra stent retriever or balloon dilation). Complications associated with stent placement included 5 migrations (39%, 1 proximal and 4 distal) and 2 incidents of cholestatic liver dysfunction associated with the compression of the bile duct orifice by expansion of FCSEMSs. In 1 patient with proximal migration, the stent was repositioned by an inflated retrieval balloon. Additional endoscopic biliary sphincterotomy with or without biliary stenting was performed in 2 patients with cholestatic liver dysfunction. There was no occurrence of pancreatic sepsis among any patients. FCSEMSs were removed from 9 of 9 patients without stent migration (100% [9/9] as per protocol, and 69% [9/13] as intention to treat, respectively). Improvement or resolution of the pancreatic ductal strictures was confirmed in all 13 patients on follow-up ERCP (2 months after stent placement), regardless of stent migration. Small patient populations without long-term follow-up. Two-month placement of FCSEMSs in patients with refractory benign pancreatic ductal strictures may be feasible and relatively safe. However, stent migration was not uncommon. A further investigation with ideal stent design may therefore be needed before recommending FCSEMSs as a therapeutic option for refractory benign pancreatic ductal strictures.

Low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors: a phase I/II report.

PubMed

Fan, Hui; Lu, Xuechun; Wang, Xiaohui; Liu, Yang; Guo, Bo; Zhang, Yan; Zhang, Wenying; Nie, Jing; Feng, Kaichao; Chen, Meixia; Zhang, Yajing; Wang, Yao; Shi, Fengxia; Fu, Xiaobing; Zhu, Hongli; Han, Weidong

2014-01-01

Aberrant DNA methylation is one of the main drivers of tumor initiation and progression. The reversibility of methylation modulation makes it an attractive target for novel anticancer therapies. Clinical studies have demonstrated that high-dose decitabine, a hypomethylating agent, results in some clinical benefits in patients with refractory advanced tumors; however, they are extremely toxic. Low doses of decitabine minimize toxicity while potentially improving the targeted effects of DNA hypomethylation. Based on these mechanisms, low-dose decitabine combined with chemoimmunotherapy may be a new treatment option for patients with refractory advanced tumors. We proposed the regimen of low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors. A favorable adverse event profile was observed in our trial that was highlighted by the finding that most of these adverse events were grades 1-2. Besides, the activity of our cohort was optimistic and the clinical benefit rate was up to 60%, and the median PFS was prolonged compared with PFS to previous treatment. We also identified a significant correlation between the PFS to previous treatment and clinical response. The low-dose DAC decitabine-based chemoimmunotherapy might be a promising protocol for improving the specificity and efficiency of patients with refractory advanced solid tumors. This trial is registered in the ClinicalTrials.gov database (identifier NCT01799083).

Clinical Characteristics of Patients with Gastroesophageal Reflux Disease Refractory to Proton Pump Inhibitors and the Effects of Switching to 20 mg Esomeprazole on Reflux Symptoms and Quality of Life

PubMed Central

Takeshima, Fuminao; Hashiguchi, Keiichi; Onitsuka, Yasunori; Tanigawa, Ken; Minami, Hitomi; Matsushima, Kayoko; Akazawa, Yuko; Shiozawa, Ken; Yamaguchi, Naoyuki; Taura, Naota; Ohnita, Ken; Ichikawa, Tatsuki; Isomoto, Hajime; Nakao, Kazuhiko

2015-01-01

Background Refractory gastroesophageal reflux disease (GERD) may deteriorate patient quality of life (QOL) despite proton pump inhibitor (PPI) therapy. Material/Methods Nineteen Japanese institutions were surveyed to determine the clinical characteristics and QOL of patients with refractory GERD. Those patients treated with a conventional PPI were switched to 20 mg esomeprazole for 4 weeks. Symptoms and QOL were assessed using Global Overall Symptom and Gastrointestinal Symptom Rating Scale (GSRS) questionnaires at baseline and at 2 and/or 4 weeks of esomeprazole treatment. Results Of 120 patients who completed the survey, 58 (48.3%) had refractory GERD. Of these, 69.0% were aged ≥65 years, 79.3% were prescribed a PPI at a standard or high dose, and 22.4% were prescribed a PPI together with another drug. After switching to esomeprazole, patients reported significant improvements in heartburn, acid regurgitation, and excessive belching at 2 weeks using a symptom diary, as well as the total score, reflux, abdominal pain, and indigestion, which were assessed using the GSRS at 4 weeks. Conclusions About half of Japanese patients with GERD may be refractory to conventional PPIs. Their reflux-related symptoms are often severe and may impair QOL. Switching to esomeprazole could be used to improve their symptoms and QOL. PMID:26719012

Minnesota Resuscitation Consortium's Advanced Perfusion and Reperfusion Cardiac Life Support Strategy for Out-of-Hospital Refractory Ventricular Fibrillation.

PubMed

Yannopoulos, Demetris; Bartos, Jason A; Martin, Cindy; Raveendran, Ganesh; Missov, Emil; Conterato, Marc; Frascone, R J; Trembley, Alexander; Sipprell, Kevin; John, Ranjit; George, Stephen; Carlson, Kathleen; Brunsvold, Melissa E; Garcia, Santiago; Aufderheide, Tom P

2016-06-13

In 2015, the Minnesota Resuscitation Consortium (MRC) implemented an advanced perfusion and reperfusion life support strategy designed to improve outcome for patients with out-of-hospital refractory ventricular fibrillation/ventricular tachycardia (VF/VT). We report the outcomes of the initial 3-month period of operations. Three emergency medical services systems serving the Minneapolis-St. Paul metro area participated in the protocol. Inclusion criteria included age 18 to 75 years, body habitus accommodating automated Lund University Cardiac Arrest System (LUCAS) cardiopulmonary resuscitation (CPR), and estimated transfer time from the scene to the cardiac catheterization laboratory of ≤30 minutes. Exclusion criteria included known terminal illness, Do Not Resuscitate/Do Not Intubate status, traumatic arrest, and significant bleeding. Refractory VF/VT arrest was defined as failure to achieve sustained return of spontaneous circulation after treatment with 3 direct current shocks and administration of 300 mg of intravenous/intraosseous amiodarone. Patients were transported to the University of Minnesota, where emergent advanced perfusion strategies (extracorporeal membrane oxygenation; ECMO), followed by coronary angiography and primary coronary intervention (PCI), were performed, when appropriate. Over the first 3 months of the protocol, 27 patients were transported with ongoing mechanical CPR. Of these, 18 patients met the inclusion and exclusion criteria. ECMO was placed in 83%. Seventy-eight percent of patients had significant coronary artery disease with a high degree of complexity and 67% received PCI. Seventy-eight percent of patients survived to hospital admission and 55% (10 of 18) survived to hospital discharge, with 50% (9 of 18) achieving good neurological function (cerebral performance categories 1 and 2). No significant ECMO-related complications were encountered. The MRC refractory VF/VT protocol is feasible and led to a high functionally favorable survival rate with few complications. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

T-111 Rankine system corrosion test loop, volume 1

NASA Technical Reports Server (NTRS)

Harrison, R. W.; Hoffman, E. E.; Smith, J. P.

1975-01-01

Results are given of a program whose objective was to determine the performance of refractory metal alloys in a two loop Rankine test system. The test system consisted of a circulating lithium circuit heated to 1230 C maximum transferring heat to a boiling potassium circuit with a 1170 C superheated vapor temperature. The results demonstrate the suitability of the selected refractory alloys to perform from a chemical compatibility standpoint.

Unusual Clinical Presentation and Role of Decompressive Craniectomy in Herpes Simplex Encephalitis.

PubMed

Singhi, Pratibha; Saini, Arushi Gahlot; Sahu, Jitendra Kumar; Kumar, Nuthan; Vyas, Sameer; Vasishta, Rakesh Kumar; Aggarwal, Ashish

2015-08-01

Decompressive craniectomy in pediatric central nervous infections with refractory intracranial hypertension is less commonly practiced. We describe improved outcome of decompressive craniectomy in a 7-year-old boy with severe herpes simplex encephalitis and medically refractory intracranial hypertension, along with a brief review of the literature. Timely recognition of refractory intracranial hypertension and surgical decompression in children with herpes simplex encephalitis can be life-saving. Additionally, strokelike atypical presentations are being increasingly recognized in children with herpes simplex encephalitis and should not take one away from the underlying herpes simplex encephalitis. © The Author(s) 2014.

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.

Cell-Free and Concentrated Ascites Reinfusion Therapy for Decompensated Liver Cirrhosis.

PubMed

Kozaki, Koichi; IInuma, Masahiro; Takagi, Tomoyuki; Fukuda, Takanori; Sanpei, Takaya; Terunuma, Yusuke; Yatabe, Yoshiharu; Akano, Kazuhiro

2016-08-01

Cell-free and concentrated ascites reinfusion therapy (CART) is expected to improve symptoms associated with refractory ascites of the decompensated liver cirrhosis patients. The aim of this study was to evaluate the safety and efficacy of the CART system performed on the decompensated liver cirrhosis patients. In this retrospective observational study, we evaluated 24 CART processes performed on 11 patients with decompensated liver cirrhosis. We evaluated the effectiveness and adverse events during CART procedures. The amounts of collected and concentrated ascites were 4491.7 ± 2222.8 mL (mean ± SD), respectively, and the concentration ratio was 22.4 ± 15.3 times, respectively. The amount of collected protein in ascites was 2.3 ± 0.5 g/dL, and concentration ratio of protein was 8.2 ± 9.4 times. Serum protein level was not significantly different between before and after CART sessions. Thus, CART allowed for the reduction of doses of albumin preparations (Alb) to be administered. CART has been reported to cause two adverse reactions: elevation of body temperature and decrease in blood pressure. In our study, decreased blood pressure was not observed even in patients with > 5 L of ascites drained. Although a transient elevation in body temperature was seen in only one patient, this febrile patient immediately returned to normal body temperature with the use of NSAIDs. In patients with refractory ascites of decompensated liver cirrhosis in whom complete cure cannot be expected, CART improves their QOL and, in terms of medical economy, allows for the reduction of doses of Alb. CART can be effectively applied as a palliative procedure for refractory ascites of decompensated liver cirrhosis patients. © 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Tailored therapy guided by multichannel intraluminal impedance pH monitoring for refractory non-erosive reflux disease.

PubMed

Ranaldo, Nunzio; Losurdo, Giuseppe; Iannone, Andrea; Principi, Mariabeatrice; Barone, Michele; De Carne, Massimo; Ierardi, Enzo; Di Leo, Alfredo

2017-09-07

A relevant percentage of non-erosive reflux disease (NERD) is refractory to proton pump inhibitors (PPIs) treatment. Multichannel intraluminal impedance pH (MII-pH) monitoring should give useful pathophysiological information about refractoriness. Therefore, our aim was to assess whether this technique could be useful to guide a 'tailored' therapy in refractory NERD. We retrospectively recruited NERD patients undergoing MII-pH monitoring for unsuccessful treatment. All patients had undergone upper endoscopy, and those with erosive esophagitis were excluded. No patient received PPI during MII-pH monitoring. Subjects were subgrouped into three categories: acid reflux, non-acid reflux and functional heartburn. MII-pH-guided therapy was performed for 4 weeks as follows: patients with acid reflux received PPI at double dose, patients with non-acid reflux PPI at full dose plus alginate four times a day and patients with functional heartburn levosulpiride 75 mg per day. A visual analog scale (VAS) ranging from 0 to 100 mm was administered before and after such tailored therapy to evaluate overall symptoms. Responders were defined by VAS improvement of at least 40%. Sixty-nine patients with refractory NERD were selected (female-male ratio 43 : 26, mean age 47.6±15.2 years). Overall effectiveness of tailored therapy was 84% without statistical difference among subgroups (88.5% acid reflux, 92% non-acid reflux, 66.6% functional heartburn; P=0.06). Univariate analysis showed that therapy failure directly correlated with functional heartburn diagnosis (OR=4.60) and suggested a trend toward a negative correlation with smoking and a positive one with nausea. However, at multivariate analysis, these parameters were not significant. Functional heartburn experienced a lower median percent VAS reduction than acid reflux (52.5% versus 66.6%, P<0.01) even if equal to non-acid reflux (66.6%). In conclusion, a tailored approach to refractory NERD, guided by MII-pH monitoring, demonstrated to be effective and should be promising to cure symptom persistence after conventional therapy failure. Nevertheless, standardized guidelines are advisable.

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.

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/.

Surgical disconnection of patent paraumbilical vein in refractory hepatic encephalopathy.

PubMed

Ishikawa, Yoshinori; Yoshida, Hiroshi; Mamada, Yasuhiro; Taniai, Nobuhiko; Bando, Koichi; Mizuguchi, Yoshiaki; Kakinuma, Daisuke; Kanda, Tomohiro; Akimaru, Koho; Tajiri, Takashi

2008-06-01

Refractory hepatic encephalopathy (HE) frequently develops in patients with cirrhosis and portal-systemic shunt. Recently, patients with refractory HE associated with portal-systemic shunt have been treated with interventional radiology. We describe a promising new treatment for portal-systemic shunt, ligation of the patent paraumbilical vein (PUV) after partial splenic embolization, in patients with refractory HE. Four patients with cirrhosis (3 women and 1 man; mean age, 56 years) and refractory HE due to a patent PUV were studied. Patency of the PUV had recurred in 1 patient after primary occlusion by interventional radiological procedures. The Child-Pugh class was B in 2 patients and C in 2. Before the present treatment, all patients had been hospitalized at least 3 times because of recurrent HE. Partial splenic embolization was performed in all patients to decrease portal venous pressure before surgery. Surgical ligation of the patent PUV was performed under epidural anesthesia. The patent PUV was carefully skeletonized and doubly ligated. Esophageal varices were evaluated with upper gastrointestinal endoscopy before and after surgery. The mean follow-up duration was 15.8 months. After ligation, there were no clinically significant complications. Esophageal varices were unchanged. The serum ammonia level was higher before surgery (162.3 +/- 56.4 mug/dL, mean +/- SD) than after surgery (41.8 +/- 20.2 mug/dL; p=0.0299). No patient had symptoms of HE. Ligation of the patent PUV is an effective treatment for patients with refractory HE.

Successful treatment of refractory TAFRO syndrome with elevated vascular endothelial growth factor using thyroxine supplements.

PubMed

Oka, Satoko; Ono, Kazuo; Nohgawa, Masaharu

2018-04-01

Although the clinical significance of hypothyroidism in TAFRO syndrome is unknown, vascular endothelial growth factor (VEGF) levels decreased with improvements in the condition of our refractory TAFRO cases after thyroxine supplement therapy. Our results indicate that elevated VEGF levels are a potential factor in the pathogenesis and anasarca of TAFRO syndrome with hypothyroidism.

Attachment system for silica tiles. [thermal protection for space shuttle orbiter

NASA Technical Reports Server (NTRS)

Dotts, R. L.; Holt, J. W. (Inventor)

1982-01-01

An improved method for markedly increasing the bond strength between a rigid, porous refractory material and non-rigid substrate by densifying the face of the rigid material opposing the substrate is discussed. Densification is accomplished by wetting the refractory material and then impregnating it with a composite slurry having a particle size to fill voids of the porous material.

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.

Adalimumab for the treatment of refractory noninfectious paediatric uveitis.

PubMed

Muñoz-Gallego, Alicia; Barral, Estefanía; Enríquez, Eugenia; Tejada, Pilar; Barceló, Ana; de Inocencio, Jaime

2017-06-01

To report the experience of our center with the use of adalimumab (ADA) for the treatment of severe refractory noninfectious paediatric uveitis. The study is a retrospective case series of all paediatric patients with refractory uveitis who were treated with ADA at the Paediatric Uveitis Unit of our center from 2008 to 2015. We present 12 patients (6 Juvenile idiopathic arthritis-associated uveitis, 4 idiopathic panuveitis, 1 early-onset sarcoidosis-associated panuveitis, and 1 intermediate uveitis), with uveitis in 19/24 eyes. Once ADA therapy was started, all the patients presented improved activity according to Standardization of Uveitis Nomenclature (SUN) criteria. Nine out of the 12 patients had structural damage before ADA could be started: cataract (n = 4), glaucoma (n = 2), cystic macular edema (n = 1), exudative retinal detachment (n = 1), and optic disk edema (n = 5). Visual acuity improved or maintained stable in 17/19 affected eyes, and only 2 eyes decreased its visual acuity because of structural damage, which was already present before ADA therapy. In our experience, ADA presents a good safety profile and is efficacious in the treatment of paediatric patients with different forms of refractory noninfectious uveitis.

Unexpected marked seizure improvement in paediatric epilepsy surgery candidates.

PubMed

Hoei-Hansen, Christina E; Mathiasen, René; Uldall, Peter

2017-02-01

Epilepsy surgery is performed based on the assumption that medical refractory epilepsy will continue. Rarely seizure freedom occurs before surgery is performed, while the patient is being evaluated as an epilepsy surgery candidate. The aim of this study was to describe the number of children withdrawn from an epilepsy surgery programme due to unexpected seizure improvement. We retrospectively studied 173 children under 18 years with medical refractory epilepsy referred for epilepsy surgery between 1996 and 2010. Medical records were reviewed in 2012 and 2015. At the first evaluation point in 2012, 13 patients were withdrawn from the epilepsy surgery programme due to unexpected marked improvement. In 2015, 6 of them were still seizure free. They had unexpected seizure freedom due to change in AED treatment (n=3) or after a febrile episode (n=3). The mean number of years they had had seizures was 3.4 years (range 0.6-6.2 years) and the number of seizures at inclusion was 209 per month (range 6-750 per month). The duration of follow-up was 6.6 years after inclusion into the epilepsy surgery programme (range 4.0-13.0 years). The aetiology of the epilepsy for these patients was heterotopia (n=1), focal cortical dysplasia (n=3), infarction (n=1) and unknown, with normal MRI (n=1). They all had an IQ in the normal range. Two of the remaining 7 children were operated later. Unexpected seizure control may occur during epilepsy surgery evaluation. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Post-operative morbidity and mortality of a cohort of steroid refractory acute severe ulcerative colitis: Nationwide multicenter study of the GETECCU ENEIDA Registry.

PubMed

Ordás, I; Domènech, E; Mañosa, M; García-Sánchez, V; Iglesias-Flores, E; Rodríguez-Moranta, F; Márquez, L; Merino, O; Fernández-Bañares, F; Gomollón, F; Vera, M; Gutiérrez, A; LLaó, J; Gisbert, J P; Aguas, M; Arias, L; Rodríguez-Lago, I; Muñoz, C; Alcaide, N; Calvet, X; Rodríguez, C; Montoro, M A; García, S; De Castro, M L; Piqueras, M; Pareja, L; Ribes, J; Panés, J; Esteve, M

2018-05-01

Despite the increased use of rescue medical therapies for steroid refractory acute severe ulcerative colitis, mortality related to this entity still remains high. We aimed to assess the mortality and morbidity related to colectomy and their predictive factors in steroid refractory acute severe ulcerative colitis, and to evaluate the changes in mortality rates, complications, indications of colectomy, and the use of rescue therapy over time. We performed a multicenter observational study of patients with steroid refractory acute severe ulcerative colitis requiring colectomy, admitted to 23 Spanish hospitals included in the ENEIDA registry (GETECCU) from 1989 to 2014. Independent predictive factors of mortality were assessed by binary logistic regression analysis. Mortality along the study was calculated using the age-standardized rate. During the study period, 429 patients underwent colectomy, presenting an overall mortality rate of 6.3% (range, 0-30%). The main causes of death were infections and post-operative complications. Independent predictive factors of mortality were: age ≥50 years (OR 23.34; 95% CI: 6.46-84.311; p < 0.0001), undergoing surgery in a secondary care hospital (OR 3.07; 95% CI: 1.01-9.35; p = 0.047), and in an emergency setting (OR 10.47; 95% CI: 1.26-86.55; p = 0.029). Neither the use of rescue medical treatment nor the type of surgical technique used (laparoscopy vs. open laparotomy) influenced mortality. The proportion of patients undergoing surgery in an emergency setting decreased over time (p < 0.0001), whereas the use of rescue medical therapy prior to colectomy progressively increased (p > 0.001). The mortality rate related to colectomy in steroid refractory acute severe ulcerative colitis varies greatly among hospitals, reinforcing the need for a continuous audit to achieve quality standards. The increasing use of rescue therapy is not associated with a worse outcome and may contribute to reducing emergency surgical interventions and improve outcomes.

Response properties of the refractory auditory nerve fiber.

PubMed

Miller, C A; Abbas, P J; Robinson, B K

2001-09-01

The refractory characteristics of auditory nerve fibers limit their ability to accurately encode temporal information. Therefore, they are relevant to the design of cochlear prostheses. It is also possible that the refractory property could be exploited by prosthetic devices to improve information transfer, as refractoriness may enhance the nerve's stochastic properties. Furthermore, refractory data are needed for the development of accurate computational models of auditory nerve fibers. We applied a two-pulse forward-masking paradigm to a feline model of the human auditory nerve to assess refractory properties of single fibers. Each fiber was driven to refractoriness by a single (masker) current pulse delivered intracochlearly. Properties of firing efficiency, latency, jitter, spike amplitude, and relative spread (a measure of dynamic range and stochasticity) were examined by exciting fibers with a second (probe) pulse and systematically varying the masker-probe interval (MPI). Responses to monophasic cathodic current pulses were analyzed. We estimated the mean absolute refractory period to be about 330 micros and the mean recovery time constant to be about 410 micros. A significant proportion of fibers (13 of 34) responded to the probe pulse with MPIs as short as 500 micros. Spike amplitude decreased with decreasing MPI, a finding relevant to the development of computational nerve-fiber models, interpretation of gross evoked potentials, and models of more central neural processing. A small mean decrement in spike jitter was noted at small MPI values. Some trends (such as spike latency-vs-MPI) varied across fibers, suggesting that sites of excitation varied across fibers. Relative spread was found to increase with decreasing MPI values, providing direct evidence that stochastic properties of fibers are altered under conditions of refractoriness.

Pharmacotherapy for Refractory and Super-Refractory Status Epilepticus in Adults.

PubMed

Holtkamp, Martin

2018-03-01

Patients with prolonged seizures that do not respond to intravenous benzodiazepines and a second-line anticonvulsant suffer from refractory status epilepticus and those with seizures that do not respond to continuous intravenous anesthetic anticonvulsants suffer from super-refractory status epilepticus. Both conditions are associated with significant morbidity and mortality. A strict pharmacological treatment regimen is urgently required, but the level of evidence for the available drugs is very low. Refractory complex focal status epilepticus generally does not require anesthetics, but all intravenous non-anesthetizing anticonvulsants may be used. Most descriptive data are available for levetiracetam, phenytoin and valproate. Refractory generalized convulsive status epilepticus is a life-threatening emergency, and long-term clinical consequences are eminent. Administration of intravenous anesthetics is mandatory, and drugs acting at the inhibitory gamma-aminobutyric acid (GABA) A receptor such as midazolam, propofol and thiopental/pentobarbital are recommended without preference for one of those. One in five patients with anesthetic treatment does not respond and has super-refractory status epilepticus. With sustained seizure activity, excitatory N-methyl-d-aspartate (NMDA) receptors are increasingly expressed post-synaptically. Ketamine is an antagonist at this receptor and may prove efficient in some patients at later stages. Neurosteroids such as allopregnanolone increase sensitivity at GABA A receptors; a Phase 1/2 trial demonstrated safety and tolerability, but randomized controlled data failed to demonstrate efficacy. Adjunct ketogenic diet may contribute to termination of difficult-to-treat status epilepticus. Randomized controlled trials are needed to increase evidence for treatment of refractory and super-refractory status epilepticus, but there are multiple obstacles for realization. Hitherto, prospective multicenter registries for pharmacological treatment may help to improve our knowledge.

Percutaneous ultrasonic tenotomy for chronic elbow tendinosis: a prospective study.

PubMed

Barnes, Darryl E; Beckley, James M; Smith, Jay

2015-01-01

Elbow tendinopathy is the most common cause of elbow pain affecting active populations. Surgical excision is reserved for patients with refractory symptoms. Percutaneous ultrasonic tenotomy performed under local anesthesia also removes degenerated tissue and therefore provides an alternative treatment option to surgical excision. This investigation prospectively documented the safety and 1-year efficacy of ultrasonic percutaneous tenotomy performed by a single operator. Nineteen patients, aged 38 to 67 years, in whom >6 months of conservative management for medial (7) or lateral (12) elbow tendinopathy had failed were prospectively studied. All patients were treated with percutaneous ultrasonic tenotomy of the elbow by a single operator. Visual analog scale (VAS) for pain, the 11-item version of the Disabilities of the Arm, Shoulder, and Hand (Quick DASH) index, and the Mayo Elbow Performance Score (MEPS) were assessed by an independent observer before treatment and at 6 weeks, 3 months, 6 months, and 12 months after treatment. No procedural complications occurred. Total treatment time was <15 minutes, and ultrasonic energy time averaged 38.6 ± 8.8 seconds per procedure. Average VAS scores were significantly improved from 6.4 to 2.6 at 6 weeks and were 0.7 at 12 months (P < .0001). Similar improvement occurred with the Quick DASH (pretreatment, 44.1; 12 months, 8.6, P < .0001) and MEPS (pretreatment, 59.1; 12 months, 83.4; P < .0001). Percutaneous ultrasonic tenotomy performed under local anesthesia appears to be a safe and effective treatment option for chronic, refractory lateral or medial elbow tendinopathy up to 1 year after the procedure. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Clozapine for Drug-Refractory Irritability in Individuals with Developmental Disability.

PubMed

Wink, Logan K; Badran, Ismail; Pedapati, Ernest V; Sorensen, Rena; Benton, Stacy C; Johnson, Mark C; Wissel, Gregory; Erickson, Craig A

2016-11-01

In this case series, we describe the acute clinical impact and tolerability of rapid titration of clozapine for treatment of refractory irritability in five hospitalized youth with developmental disability. We offer this descriptive report in an effort to expand the evidence base guiding treatment of refractory aggression in this population. Five youth with developmental disability and severe irritability were admitted to a 10-bed psychiatric crisis stabilization unit where they received thorough psychiatric and medical evaluation. Informed consent was obtained in each case, and each patient underwent rapid titration onto clozapine. Clozapine monitoring guidelines were followed for all patients throughout treatment, and clinical severity at baseline and improvement with treatment was measured by use of the Clinical Global Impressions-Severity scale (CGI-S) and the Clinical Global Impressions-Improvement scale (CGI-I). One female and four males diagnosed with developmental disability and at least one other psychiatric diagnosis, mean age of 13.1 ± 2.1 years, and mean CGI-S at baseline of 5.8, each received clozapine treatment by rapid titration. The mean therapeutic total daily dose of clozapine was 380 ± 200 mg. All patients demonstrated acute clinical improvement with the mean final CGI-I of 2.0, or "much improved." These initial results support the potential utility of clozapine rapid titration for treatment of severe refractory irritability in youth with developmental disability. These patients tolerated clozapine treatment in the short term. Future studies are needed to thoroughly evaluate the long-term safety of clozapine treatment in this population.

Allogeneic hematopoietic stem cell transplantation for severe, refractory juvenile idiopathic arthritis

PubMed Central

Ladomenou, Fani; Carpenter, Ben; Chandra, Sharat; Sedlacek, Petr; Formankova, Renata; Grandage, Vicky; Friswell, Mark; Cant, Andrew J.; Nademi, Zohreh; Slatter, Mary A.; Gennery, Andrew R.; Hambleton, Sophie; Flood, Terence J.; Lucchini, Giovanna; Chiesa, Robert; Rao, Kanchan; Amrolia, Persis J.; Brogan, Paul; Wedderburn, Lucy R.; Glanville, Julie M.; Hough, Rachael; Marsh, Rebecca; Abinun, Mario; Veys, Paul

2018-01-01

Patients with juvenile idiopathic arthritis (JIA) can experience a severe disease course, with progressive destructive polyarthritis refractory to conventional therapy with disease-modifying antirheumatic drugs including biologics, as well as life-threatening complications including macrophage activation syndrome (MAS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative immunomodulatory strategy for patients with such refractory disease. We treated 16 patients in 5 transplant centers between 2007 and 2016: 11 children with systemic JIA and 5 with rheumatoid factor–negative polyarticular JIA; all were either refractory to standard therapy, had developed secondary hemophagocytic lymphohistiocytosis/MAS poorly responsive to treatment, or had failed autologous HSCT. All children received reduced toxicity fludarabine-based conditioning regimens and serotherapy with alemtuzumab. Fourteen of 16 patients are alive with a median follow-up of 29 months (range, 2.8-96 months). All patients had hematological recovery. Three patients had grade II-IV acute graft-versus-host disease. The incidence of viral infections after HSCT was high, likely due to the use of alemtuzumab in already heavily immunosuppressed patients. All patients had significant improvement of arthritis, resolution of MAS, and improved quality of life early following allo-HSCT; most importantly, 11 children achieved complete drug-free remission at the last follow-up. Allo-HSCT using alemtuzumab and reduced toxicity conditioning is a promising therapeutic option for patients with JIA refractory to conventional therapy and/or complicated by MAS. Long-term follow-up is required to ascertain whether disease control following HSCT continues indefinitely. PMID:29618462

Rehabilitation of the dominance of maxillary central incisors with refractory porcelain veneers requiring minimal tooth preparation.

PubMed

da Cunha, Leonardo Fernandes; Gonzaga, Carla Castiglia; Saab, Rafaella; Mushashe, Amanda Mahammad; Correr, Gisele Maria

2015-01-01

Central dominance is an important element of an esthetic smile. Color, form, and size have been suggested as tools for assessing the dominance of maxillary teeth. A spectrophotometer can be used to determine the value, hue, and chroma. Correct sizing of restorations according to the central incisor dominance principle improves not only esthetics but also aspects of occlusion, such as anterior guidance. Refractory porcelain systems can effectively restore the color, shape, emergence profile, and incisal translucency. This report illustrates the esthetic and occlusal rehabilitation of the dominance of maxillary central incisors using fabricated minimal thickness refractory porcelain veneers.

Spontaneous growth of polarizing refractory metal ‘nano-fins’

NASA Astrophysics Data System (ADS)

Tai, M. C.; Gentle, A. R.; Arnold, M. D.; Cortie, M. B.

2018-03-01

Traditional polymer polarizers degrade in harsh environments and at high temperatures, reducing the polarization effect. In contrast, polarizers produced with refractory metals have vastly improved thermal stability and resistance to harsh environments but are expensive to fabricate. Here we demonstrate prototype refractory metal wire grid polarizers produced by co-sputtering molybdenum and aluminum under specific conditions. Removal of the aluminum through selective dissolution enables the nanostructure array to transmit light. The polarization spans 500-1100 nm and the extinction ratio significantly increases to >100. Possessing broadband polarization and sufficient extinction ratios, the new polarizing film has potential applications in coatings for sunglasses, windows, pyrometers, scientific instruments, and LCD panels.

Improving volatile fatty acids production by exploiting the residual substrates in post-fermented sludge: Protease catalysis of refractory protein.

PubMed

Yin, Bo; Liu, Hongbo; Wang, Yuanyuan; Bai, Jie; Liu, He; Fu, Bo

2016-03-01

The real cause to the low yield of volatile fatty acids (VFAs), from inhibition or low biodegradation, is uncertain in sludge anaerobic fermentation. In this study, poor biodegradability of proteins and fast decrease of the indigenous hydrolase activity in the residual post-fermented sludge were found to be the major reasons. With the addition of trypsin or alkaline protease in residual post-fermented sludge after primary alkaline fermentation, degradation efficiency of refractory protein increased by 33.6% and 34.8%, respectively. Accordingly, the VFAs yields were improved by 69.7% and 106.1%, respectively. Furthermore, the activities of added trypsin and alkaline protease could maintain at 13.52 U/mL and 19.11 U/mL in the alkaline fermentation process. This study demonstrated that exploiting the refractory proteins in residual post-fermented sludge by protease addition seems to be a very promising way for improving VFAs yield of conventional alkaline fermentations with waste activated sludge. Copyright © 2015 Elsevier Ltd. All rights reserved.

Human cytomegalovirus and Epstein-Barr virus infection in inflammatory bowel disease: need for mucosal viral load measurement.

PubMed

Ciccocioppo, Rachele; Racca, Francesca; Paolucci, Stefania; Campanini, Giulia; Pozzi, Lodovica; Betti, Elena; Riboni, Roberta; Vanoli, Alessandro; Baldanti, Fausto; Corazza, Gino Roberto

2015-02-14

To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infection in inflammatory bowel disease (IBD). A cohort of 40 IBD patients (17 refractory) and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest. Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry, and correlations with clinical and endoscopic indexes of activity, and risk factors were investigated. All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as compared to 13/23 (56.5%) non-refractory and 13/40 (32.5%) controls. The median DNA value was significantly higher in refractory (HCMV 286 and EBV 5.440 copies/10(5) cells) than in non-refractory (HCMV 0 and EBV 6 copies/10(5) cells; P < 0.05 and < 0.001) IBD patients and controls (HCMV and EBV 0 copies/10(5) cells; P < 0.001 for both). Refractory patients showed DNA peak values ≥ 10(3) copies/10(5) cells in diseased mucosa in comparison to non-diseased mucosa (P < 0.0121 for HCMV and < 0.0004 for EBV), while non-refractory patients and controls invariably displayed levels below this threshold, thus allowing us to differentiate viral colitis from mucosal infection. Moreover, the mucosal load positively correlated with the values found in the peripheral blood, whilst no correlation with the number of positive cells at immunohistochemistry was found. Steroid use was identified as a significant risk factor for both HCMV (P = 0.018) and EBV (P = 0.002) colitis. Finally, a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis, whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications. Viral colitis appeared to contribute to mucosal lesions in refractory IBD, and its correct diagnosis and management require quantitative real-time polymerase chain reaction assay of mucosal specimens.

Hematopoietic stem cell transplantation for non-Hodgkin lymphoma.

PubMed

Bhatt, Vijaya Raj; Vose, Julie M

2014-12-01

Up-front rituximab-based chemotherapy has improved outcomes in non-Hodgkin lymphoma (NHL); refractory or relapsed NHL still accounts for approximately 18,000 deaths in the United States. Autologous hematopoietic stem cell transplantation (SCT) can improve survival in primary refractory or relapsed aggressive NHL and mantle cell lymphoma and in relapsed follicular or peripheral T-cell lymphoma. Autologous SCT as a consolidation therapy after first complete or partial remission in high-risk aggressive NHL, mantle cell lymphoma, and peripheral T-cell lymphoma may improve progression-free survival. Allogeneic SCT offers a lower relapse rate but a higher nonrelapse mortality resulting in overall survival similar to autologous SCT. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Evolving Concepts in Posterior Subthalamic Area Deep Brain Stimulation for Treatment of Tremor: Surgical Neuroanatomy and Practical Considerations.

PubMed

Ramirez-Zamora, Adolfo; Smith, Heather; Kumar, Vignessh; Prusik, Julia; Phookan, Sujoy; Pilitsis, Julie G

2016-01-01

Although thalamic deep brain stimulation (DBS) has been established as an effective therapy for refractory tremor in Parkinson's disease and essential tremor, reports investigating the efficacy of posterior subthalamic area (PSA) DBS for severe, debilitating tremors continue to emerge. However, questions regarding the optimal anatomical target, surgical approach, programming paradigms and effectiveness compared to other targets remain. In this report, we aimed to review the current literature to assess different stereotactic techniques, anatomical considerations, adverse effects and stimulation settings in PSA DBS. A comprehensive literature review was performed searching for articles discussing tremors and PSA stimulation. We performed a quantitative analysis comparing different DBS tremor targets. Tremor improvement is consistently documented in most reports with an average reduction in tremor of 79% depending on the specific tremor syndrome. Tremor benefit in patients with multiple sclerosis (MS) tremor was significantly higher than for other stimulation targets. Transient paresthesias, imbalance, dizziness and dysarthria are the most common side effects with PSA DBS. PSA DBS is an effective and safe treatment for tremor control and should be considered in patients with refractory tremors with associated cerebellar or dystonic features, proximal tremors and MS tremor. © 2016 S. Karger AG, Basel.

Test model designs for advanced refractory ceramic materials

NASA Technical Reports Server (NTRS)

Tran, Huy Kim

1993-01-01

The next generation of space vehicles will be subjected to severe aerothermal loads and will require an improved thermal protection system (TPS) and other advanced vehicle components. In order to ensure the satisfactory performance system (TPS) and other advanced vehicle materials and components, testing is to be performed in environments similar to space flight. The design and fabrication of the test models should be fairly simple but still accomplish test objectives. In the Advanced Refractory Ceramic Materials test series, the models and model holders will need to withstand the required heat fluxes of 340 to 817 W/sq cm or surface temperatures in the range of 2700 K to 3000 K. The model holders should provide one dimensional (1-D) heat transfer to the samples and the appropriate flow field without compromising the primary test objectives. The optical properties such as the effective emissivity, catalytic efficiency coefficients, thermal properties, and mass loss measurements are also taken into consideration in the design process. Therefore, it is the intent of this paper to demonstrate the design schemes for different models and model holders that would accommodate these test requirements and ensure the safe operation in a typical arc jet facility.

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

Improved high temperature refractory. [MgCr/sub 2/O/sub 4/ composite with ZrO/sub 2/

DOEpatents

Singh, J.P.; James, J.; Picciolo, J.J.

1985-12-10

A high chromia refractory composite has been developed with improved thermal shock resistance and containing about 5 to 30 wt % of unstabilized ZrO/sub 2/ having a temperature-dependent phase change resulting in large expansion mismatch between the ZrO/sub 2/ and the chromia matrix which causes microcracks to form during cooling in the high chromia matrix. The particle size preferably is primarily between about 0.6 to 5 microns and particularly below about 3 microns with an average size in the order of 1.2 to 1.8 microns.

Clinical Outcomes, Efficacy, and Adverse Events in Patients Undergoing Esophageal Stent Placement for Benign Indications: A Large Multicenter Study.

PubMed

Suzuki, Takayuki; Siddiqui, Ali; Taylor, Linda J; Cox, Kristen; Hasan, Raza A; Laique, Sobia N; Mathew, Arun; Wrobel, Piotr; Adler, Douglas G

2016-01-01

Esophageal stents are commonly used to treat benign esophageal conditions including refractory benign esophageal strictures, anastomotic strictures, fistulae, perforations and anastomotic leaks. Data on outcomes in these settings remain limited. We performed a retrospective multicenter study of patients who underwent fully or partially covered self-expandable stent placement for benign esophageal diseases. Esophageal stent placements were performed for the following indications: (1) benign refractory esophageal strictures, (2) surgical anastomotic strictures, (3) esophageal perforations, (4) esophageal fistulae, and (5) surgical anastomotic leaks. A total of 70 patients underwent esophageal stent placement for benign esophageal conditions. A total of 114 separate procedures were performed. The most common indication for esophageal stent placement was refractory benign esophageal stricture (48.2%). Global treatment success rate was 55.7%. Treatment success rate was 33.3% in refractory benign strictures, 23.1% in anastomotic strictures, 100% in perforations, 71.4% in fistulae, and 80% in anastomotic leaks. Stent migration was noted in 28 of 70 patients (40%), most commonly seen in refractory benign strictures. This is one of the largest studies to date of esophageal stents to treat benign esophageal diseases. Success rates are lowest in benign esophageal strictures. These patients have few other options beyond chronic dilations, feeding tubes, and surgery, and fully covered self-expandable metallic stent give patients a chance to have their problem fixed endoscopically and still eat by mouth. Perforations, fistulas, and leaks respond very well to esophageal stenting, and stenting should be considered as a first-line therapy in these settings.

Long-term treatment of epilepsy with everolimus in tuberous sclerosis

PubMed Central

Wilfong, Angus A.; Mays, Maxwell; Talley, Christina M.; Agricola, Karen; Tudor, Cindy; Capal, Jamie; Holland-Bouley, Katherine; Franz, David Neal

2016-01-01

Objective: To evaluate the long-term benefit and safety of everolimus for the treatment of medically refractory epilepsy in patients with tuberous sclerosis complex (TSC). Methods: Everolimus was titrated over 4 weeks and continued an additional 8 weeks in a prospective, open-label, phase I/II clinical trial design. Participants demonstrating initial benefit continued treatment until study completion (48 months). The primary endpoint was percentage of patients with a ≥50% reduction in seizure frequency compared to baseline. Secondary endpoints assessed absolute seizure frequency, adverse events (AEs), behavior, and quality of life. Results: Of the 20 participants who completed the initial study phase, 18 continued extended treatment. Fourteen of 18 (78%) participants completed the study, all but 1 of whom reported ≥50% reduction in seizure frequency at 48 months. All participants reported at least 1 AE, the vast majority (94%) of which were graded mild or moderate severity. Improvements in behavior and quality of life were also observed, but failed to achieve statistical significance at 48 months. Conclusions: Improved seizure control was maintained for 4 years in the majority of patients with TSC with medically refractory epilepsy treated with everolimus. Long-term treatment with everolimus is safe and well-tolerated in this population. Everolimus may be a therapeutic option for refractory epilepsy in TSC. Classification of evidence: This study provides Class IV evidence that for patients with TSC with medically refractory epilepsy everolimus improves seizure control. PMID:27815402

[Allogeneic haematopoietic cell transplantation for indolent lymphomas: Guidelines from the Francophone Society Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

PubMed

Gauthier, Jordan; Chantepie, Sylvain; Bouabdallah, Krimo; Jost, Edgar; Nguyen, Stéphanie; Gac, Anne-Claire; Damaj, Gandhi; Duléry, Rémy; Michallet, Mauricette; Delage, Jérémy; Lewalle, Philippe; Morschhauser, Franck; Salles, Gilles; Yakoub-Agha, Ibrahim; Cornillon, Jérôme

2017-12-01

Despite great improvements in the outcome of patients with lymphoma, some may still relapse or present with primary refractory disease. In these situations, allogeneic hematopoietic cell transplantation is a potentially curative option, this is true particularly the case of relapse after autologous stem cell transplantation. Recently, novel agents such as anti-PD1 and BTK inhibitors have started to challenge the use of allogeneic hematopoietic cell transplantation for relapsed or refractory lymphoma. During the 2016 annual workshop of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), we performed a comprehensive review of the literature published in the last 10 years and established guidelines to clarify the indications and transplant modalities in this setting. This paper specifically reports on our conclusions regarding indolent lymphomas, mainly follicular lymphoma and chronic lymphocytic leukemia. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Reusable Surface Insulation Tile Thermal Protection Materials: Past, Present and the Future

NASA Technical Reports Server (NTRS)

Leiser, Daniel B.; Stewart, David A.; Venkatapathy, Ethiras (Technical Monitor)

2002-01-01

Silica (LI-900) Reusable Surface Insulation (RSI) tile have been used on the majority of the Shuttle since its initial flight. Its overall performance with Reaction Cured Glass (RCG) coating applied will be reviewed. Improvements in insulations, Fibrous Refractory Composite Insulation (FRCI-12) and Alumina Enhanced Thermal Barrier (AETB-8) and coatings/surface treatments such as Toughened Uni-Piece Fibrous Insulation (TUFI) have been developed and successfully applied. The performance of these enhancements on the Shuttle Orbiters over the past few years along with the next version of tile materials, High Efficiency Tantalum-based Ceramic (HETC) with even broader applicability will also be discussed.

Oral tranexamic acid lightens refractory melasma.

PubMed

Tan, Aaron Wei Min; Sen, Priya; Chua, Sze Hon; Goh, Boon Kee

2017-08-01

Melasma is a common acquired hyperpigmentary disorder, particularly among Asians and Hispanics, but its exact pathomechanism is poorly understood. Tranexamic acid has been found to lighten melasma by interfering with the interaction of melanocytes and keratinocytes by inhibiting the plasminogen/plasmin system. The aim was to evaluate the therapeutic effects of oral tranexamic acid in the treatment of melasma refractory to topical skin-lightening agents. This retrospective study analyses patients with melasma recruited from a tertiary dermatological centre in Singapore between 1 August 2009 and 31 March 2011. The patients chosen had refractory melasma treated with oral tranexamic acid 250 mg twice daily in addition to pre-existing combination topical therapy. Objective assessment using the physician's global assessment and melasma area and severity index (MASI) scores were performed based on a post-hoc analysis of photographic records by three independent physicians. A paired t-test was used to evaluate the changes in the MASI scores pre-therapy and post-treatment. Statistical significance was defined as P < 0.05. Altogether 25 patients were treated with tranexamic acid for a mean period of 3.7 ± 0.33 months, in addition to combination topical therapy. Their mean age was 47.2 ± 1.61 years. The mean MASI scores after tranexamic acid treatment (2.7 ± 1.6) were significantly lower (P < 0.01) than those prior to treatment (8.8 ± 4.2). The mean improvement in scores was 69%. The follow-up period was up to 6 months. Low-dose oral tranexamic acid can serve as a safe and useful adjunct in the treatment of refractory melasma. © 2016 The Australasian College of Dermatologists.

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.

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.

Therapeutic Response to Twice-daily Rabeprazole on Health-related Quality of Life and Symptoms in Patients with Refractory Reflux Esophagitis: A Multicenter Observational Study

PubMed Central

Kinoshita, Yoshikazu; Hongo, Michio; Kusano, Motoyasu; Furuhata, Yoshinori; Miyagishi, Hideaki; Ikeuchi, Satoshi

2017-01-01

Objective To investigate the effect of twice-daily rabeprazole doses on health-related quality of life in refractory patients. Methods and Patients Reflux esophagitis patients with an insufficient response to once-daily proton pump inhibitor therapy (Los Angeles Classification grade A-D) received rabeprazole 10 mg or 20 mg twice daily for 8 weeks. The health-related quality of life (SF-8™) and symptoms, using the Frequency Scale for the Symptoms of Gastroesophageal reflux disease, were evaluated before treatment and at weeks 4 and 8. Endoscopy was performed at baseline and at weeks 8 and 32 where possible. The rabeprazole dose was determined by the attending physician. Results There were 1,796 patients analyzed for the efficacy of the twice-daily treatment. Of these cases, 1,462 were treated with rabeprazole 10 mg twice daily, and 334 were treated with rabeprazole 20 mg twice daily. The factors that affected the selection of the twice-daily rabeprazole dose by physicians were evaluated, and as expected, “endoscopic findings when treatment was started” had a strong effect on the selection of the rabeprazole dose. With both regimens, health-related quality of life and subjective symptoms were significantly improved at weeks 4 and 8 compared to baseline (p<0.001). The recurrence rate of erosive esophagitis at week 32 was 9.7% in rabeprazole twice daily-treated patients and 28.4% in proton pump inhibitor (PPI) once daily-treated patients. Both regimens were well tolerated. Conclusion Twice-daily treatment with rabeprazole improved the subjective symptoms and health-related quality of life in patients with refractory reflux esophagitis more effectively than the standard once-daily dose. PMID:28502925

Corrosion resistance of ceramic refractories to simulated waste glasses at high temperature

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

Xing, S.B.; Lin, Y.; Mohr, R.K.

1996-08-01

In many vitrification processes, refractory materials are used to contain the waste glass melt. The corrosive nature of the high-temperature melt consumes the waste feed materials but also limits refractory life. As vitrification is applied to more diverse waste streams, and particularly in higher-temperature applications, increasingly severe demands are placed on the refractory materials. A variety of potential refractory materials including Fused-cast AZS, Monofrax K3, Monofrax E, and the Corhart refractories ER1195, ER2161, C1215, C1215Z, Rechrome, and T1186, were subjected to corrosion testing at 1,450 C using the ASTM C-621 procedure. A series of simulated waste glasses was used whichmore » included F, Cl, S, Cu, Zn, Pb; these minor components were found to cause significant, and in some cases drastic, increases in corrosion rates. The corrosion tests were conducted over a range of time intervals extending to 144 hrs in order to investigate the kinetics of the corrosion processes. The change of the concentrations of constituents in the glass was monitored by compositional analysis of glass samples and correlated to the observed extent of corrosion; typically, components of the material under test increase with time while key minor components, such as Co and Pb, decrease. The rate of corrosion of high-zirconia refractories was slowed considerably by adding zirconia to the waste glass composition; this has the added benefit of improving the aqueous leach resistance of the waste form that is produced.« less

Interactions of Alumina-Based and Magnesia-Based Refractories with Iron Melts and Slags: A Review

NASA Astrophysics Data System (ADS)

Sarkar, R.; Sohn, H. Y.

2018-06-01

A novel flash ironmaking technology (FIT) based on the direct reduction of iron ore concentrate with a reductant gas (such as hydrogen, natural gas, coal gas, or a combination thereof) in a flash furnace is being developed at the University of Utah. This technology which is undergoing large-scale laboratory testing aims at overcoming the limitations of blast furnace ironmaking by bypassing the problematic pelletization/sintering and cokemaking steps.[1-5] Refractory selection is expected to play an important step in the development of FIT and its proposed scale-up. For nominating an appropriate refractory for the FIT, understanding the interactions of candidate refractories with iron/iron oxide and slags under H2/CO/CO2/H2O environments is necessary. This work is undertaken to review the existing literature on the interactions of important refractories with iron melts and relevant slags with an emphasis on two of the most commonly used refractories in ironmaking and steelmaking applications: the alumina-based refractories (used widely in blast furnace operations) and the magnesia-based refractories (used extensively in primary as well as secondary steelmaking). First, a comprehensive review on the interactions of alumina-based refractories with iron melts and slags has been done. Next the existing literature on the interactions of magnesia-based refractories with iron melts and relevant slags has been reviewed. Summaries have been included after each section and sub-section along with comments and critical insights from the authors. Finally, in the concluding remarks the differences in operating conditions between existing iron and steelmaking practices and the novel FIT have been highlighted. On the basis of these differences, it has been argued that the results and conclusions available from previous studies on refractory-metal-slag interactions are of little significance to flash ironmaking. Thus, there exists a need to carry out laboratory experiments for evaluating refractory performance in flash ironmaking under conditions relevant to the current process (FIT).

Testing Requirements for Refractory Materials

NASA Technical Reports Server (NTRS)

Calle, Luz Marina; Hintze, Paul E.; Parlier, Christopher R.; Curran, Jerome P.; Kolody, Mark R.; Sampson, Jeffrey W.; Montgomery, Eliza M.

2011-01-01

Launch Pads 39A and 39B currently use refractory material (Fondu Fyre) in the flame trenches. This material was initially approved for the Saturn program. This material had a lifetime of 10 years according to the manufacturer, and it has been used for over 40 years. As a consequence, the Fondu Fyre at Launch Complex 39 requires repair subsequent to almost every launch. A review of the literature indicates that the gunned Fondu Fyre refractory product (WA-1G) was never tested prior to use. With the recent severe damage to the flame trenches, a new refractory material is sought to replace Fondu Fyre. In order to replace Fondu Fyre, a methodology to test and evaluate refractory products was developed. This paper outlines this methodology and discusses current testing requirements, as well as the laboratory testing that might be required. Furthermore, this report points out the necessity for subscale testing, the locations where this testing can be performed, and the parameters that will be necessary to qualify a product. The goal is to identify a more durable refractory material that has physical, chemical, and thermal properties suitable to withstand the harsh environment of the launch pads at KSC.

Testing Requirements for Refractory Materials

NASA Technical Reports Server (NTRS)

Calle, Luz Marina; Hintze, Paul E.; Parlier, Christopher R.; Curran, Jerome P.; Kolody, Mark R.; Sampson, Jeffrey W.; Montgomery, Eliza M.

2010-01-01

Launch Pads 39A and 39B currently use refractory material (Fondu Fyre) in the flame trenches. This material was initially approved for the Saturn program. This material had a lifetime of 10 years according to the manufacturer, and it has been used for over 40 years. As a consequence, the Fondu Fyre at Launch Complex 39 requires repair subsequent to almost every launch. A review of the literature indicates that the gunned Fondu Fyre refractory product (WA-1G) was never tested prior to use. With the recent severe damage to the flame trenches, a new refractory material is sought to replace Fondu Fyre. In order to replace Fondu Fyre, a methodology to test and evaluate refractory products was developed. This paper outlines this methodology and discusses current testing requirements, as well as the laboratory testing that might be required. Furthermore, this report points out the necessity for subscale testing, the locations where this testing can be performed, and the parameters that will be necessary to qualify a product. The goal is to identify a more durable refractory material that has physical, chemical, and thermal properties suitable to withstand the harsh environment of the launch pads at KSC.

Testing Requirements for Refractory Materials

NASA Technical Reports Server (NTRS)

Calle, Luz Marina; Hintze, Paul E.; Parlier, Christopher R.; Curran, Jerome P.; Kolody, Mark R.; Sampson, Jeffrey W,; Montgomery, Eliza M.

2012-01-01

Launch Pads 39A and 39B currently use refractory material (Fondu Fyre) in the flame trenches. This material was initially approved for the Saturn program. This material had a lifetime of 10years according to the manufacturer, and it has been used for over 40 years. As a consequence, the Fondu Fyre at Launch Complex 39 requires repair subsequent to almost every launch. A review of the literature indicates that the gunned Fondu Fyre refractory product (WA-1 G) was never tested prior to use. With the recent severe damage to the flame trenches, a new refractory material is sought to replace Fondu Fyre. In order to replace Fondu Fyre, a methodology to test and evaluate refractory products was developed. This paper outlines this methodology and discusses current testing requirements, as well as the laboratory testing that might be required. Furthermore, this report points out the necessity for subscale testing, the locations where this testing can be performed, and the parameters that will be necessary to qualify a product. The goal is to identify a more durable refractory material that has physical, chemical, and thermal properties suitable to withstand the harsh environment of the launch pads at KSC.

Efficacy of Enhanced External Counterpulsation in Patients With Chronic Refractory Angina on Canadian Cardiovascular Society (CCS) Angina Class: An Updated Meta-Analysis.

PubMed

Zhang, Chunmei; Liu, Xiangjuan; Wang, Xiaomeng; Wang, Qi; Zhang, Yun; Ge, Zhiming

2015-11-01

A growing number of patients with chronic artery disease suffer from angina, despite the optimal medical management (ie, β-blockers, calcium channel blockers, and long-acting nitrates) and revascularization. Currently, enhanced external counterpulsation (EECP) therapy has been verified as a noninvasive, safe therapy for refractory angina. The study was designed to evaluate the efficacy of EECP in patients with chronic refractory angina according to Canadian Cardiovascular Society (CCS) angina class.We identified systematic literature through MEDLINE, EMBASE, the Cochrane Clinical Trials Register Database, and the ClinicalTrials. gov Website from 1990 to 2015. Studies were considered eligible if they were prospective and reported data on CCS class before and after EECP treatment. Meta-analysis was performed to assess the efficacy of EECP therapy by at least 1 CCS angina class improvement, and proportion along with the 95% confidence interval (CI) was calculated. Statistical heterogeneity was calculated by I statistic and the Q statistic. Sensitivity analysis was addressed to test the influence of trials on the overall pooled results. Subgroup analysis was applied to explore potential reasons for heterogeneity.Eighteen studies were enrolled in our meta-analysis. Pooled analysis showed 85% of patients underwent EECP had a reduction by at least one CCS class (95%CI 0.81-0.88, I = 58.5%, P < 0.001). The proportion of patients enrolled at primarily different studies with chronic heart failure (CHF) improved by at least 1 CCS class was about 84% after EECP (95%CI 0.81-0.88, I = 32.7%, P = 0.1668). After 3 large studies were excluded, the pooled proportion was 82% (95%CI 0.79-0.86, I = 18%, P = 0.2528). Funnel plot indicated that some asymmetry while the Begg and Egger bias statistic showed no publication bias (P = 0.1495 and 0.2859, respectively).Our study confirmed that EECP provided an effective treatment for patients who were unresponsive to medical management and/or invasive therapy. However, the long-term benefits of EECP therapy needed further studies to evaluate in the management of chronic refractory angina.

Sacral nerve root neuromodulation: an effective treatment for refractory urge incontinence.

PubMed

Shaker, H S; Hassouna, M

1998-05-01

Sacral foramina implants have been recognized recently as a method for treatment of refractory urinary urge incontinence. We study the outcome of the procedure with in-depth analysis of the results of 18 implanted cases. Patients with urinary urge incontinence were subjected to percutaneous nerve evaluation of the S3 roots as a temporary screening test to determine response to neuromodulation. Satisfactory responders were implanted with permanent sacral root neuroprosthesis. The study design included comprehensive voiding diaries for 4 consecutive days twice as a baseline, 1 with percutaneous nerve evaluation screening, 1 after the percutaneous nerve evaluation, 1 at the 1, 3 and 6 post-implantation visits, and every 6 months thereafter. Uroflowmetry and quality of life questionnaires were performed at the same intervals. Urodynamic study was done as a baseline and 6 months after implantation of the neuroprosthesis. All 18 patients (16 women and 2 men) with refractory urge incontinence received a sacral foramina neuroprosthesis after demonstrating a good response to the percutaneous nerve evaluation. Average patient age at presentation was 42.3+/-3.3 years (range 22 to 67) and duration of urinary symptoms was 6.6+/-1.3 years (range 1.2 to 18.8). Average followup was 18.8 months (range 3 to 83). Neuromodulation in these patients showed a marked reduction in leakage episodes from 6.49 to 1.98 times per 24 hours and in the leakage severity score. Eight patients became completely dry and 4 had average leakage episodes of 1 or less daily. Patients showed as well a decrease in urinary frequency with an increase in functional bladder capacity. Associated pelvic pain improved substantially. Cystometrograms demonstrated increased volume at first sensation by 50% and increased cystometric capacity by 15% with the disappearance of uninhibited contractions in 1 of the 4 patients who presented with it preoperatively. There was also noticeable improvement in the quality of life. Complication rate was low and none was life threatening. Sacral root neuromodulation is an appealing modality for treatment of urge incontinence refractory to conventional pharmacotherapy. The relative simplicity of the technique, promising results and low complication rate make this therapy a likely alternative.

Anti-TNF-α therapy in patients with refractory uveitis due to Behçet's disease: a 1-year follow-up study of 124 patients.

PubMed

Calvo-Río, Vanesa; Blanco, Ricardo; Beltrán, Emma; Sánchez-Bursón, Juán; Mesquida, Marina; Adán, Alfredo; Hernandez, María Victoria; Hernandez Garfella, Marisa; Valls Pascual, Elia; Martínez-Costa, Lucía; Sellas-Fernández, Agustí; Cordero Coma, Miguel; Díaz-Llopis, Manuel; Gallego, Roberto; Salom, David; García Serrano, José L; Ortego, Norberto; Herreras, José M; Fonollosa, Alejandro; García-Aparicio, Angel M; Maíz, Olga; Blanco, Ana; Torre, Ignacio; Fernández-Espartero, Cruz; Jovani, Vega; Peiteado-Lopez, Diana; Pato, Esperanza; Cruz, Juan; Fernández-Cid, Carlos; Aurrecoechea, Elena; García, Miriam; Caracuel, Miguel A; Montilla, Carlos; Atanes, Antonio; Hernandez, Félix Francisco; Insua, Santos; González-Suárez, Senén; Sánchez-Andrade, Amalia; Gamero, Fernando; Linares, Luis; Romero-Bueno, Fredeswinda; García, A Javier; Almodovar, Raquel; Minguez, Enrique; Carrasco Cubero, Carmen; Olive, Alejandro; Vázquez, Julio; Ruiz Moreno, Oscar; Jiménez-Zorzo, Fernando; Manero, Javier; Muñoz Fernández, Santiago; Rueda-Gotor, Javier; González-Gay, Miguel A

2014-12-01

The aim of this study was to assess the efficacy of anti-TNF-α therapy in refractory uveitis due to Behçet's disease (BD). We performed a multicentre study of 124 patients with BD uveitis refractory to conventional treatment including high-dose corticosteroids and at least one standard immunosuppressive agent. Patients were treated for at least 12 months with infliximab (IFX) (3-5 mg/kg at 0, 2 and 6 weeks and then every 4-8 weeks) or adalimumab (ADA) (usually 40 mg every 2 weeks). The main outcome measures were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness and immunosuppression load. Sixty-eight men and 56 women (221 affected eyes) were studied. The mean age was 38.6 years (s.d. 10.4). HLA-B51 was positive in 66.1% of patients and uveitis was bilateral in 78.2%. IFX was the first biologic agent in 77 cases (62%) and ADA was first in 47 (38%). In most cases anti-TNF-α drugs were used in combination with conventional immunosuppressive drugs. At the onset of anti-TNF-α therapy, anterior chamber and vitreous inflammation was observed in 57% and 64.4% of patients, respectively. In both conditions the damage decreased significantly after 1 year. At baseline, 50 patients (80 eyes) had macular thickening [optical coherence tomography (OCT) >250 μm] and 35 (49 eyes) had cystoid macular oedema (OCT>300 μm) that improved from 420 μm (s.d. 119.5) at baseline to 271 μm (s.d. 45.6) at month 12 (P < 0.01). The best-corrected visual acuity and the suppression load also showed significant improvement. After 1 year of follow-up, 67.7% of patients were inactive. Biologic therapy was well tolerated in most cases. Anti-TNF-α therapy is effective and relatively safe in refractory BD uveitis. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

Catalytic, hollow, refractory spheres, conversions with them

NASA Technical Reports Server (NTRS)

Wang, Taylor G. (Inventor); Elleman, Daniel D. (Inventor); Lee, Mark C. (Inventor); Kendall, Jr., James M. (Inventor)

1989-01-01

Improved, heterogeneous, refractory catalysts are in the form of gas-impervious, hollow, thin-walled spheres (10) suitable formed of a shell (12) of refractory such as alumina having a cavity (14) containing a gas at a pressure greater than atmospheric pressure. The wall material may be itself catalytic or a catalytically active material coated onto the sphere as a layer (16), suitably platinum or iron, which may be further coated with a layer (18) of activator or promoter. The density of the spheres (30) can be uniformly controlled to a preselected value within .+-.10 percent of the density of the fluid reactant such that the spheres either remain suspended or slowly fall or rise through the liquid reactant.

Catalytic, hollow, refractory spheres

NASA Technical Reports Server (NTRS)

Wang, Taylor G. (Inventor); Elleman, Daniel D. (Inventor); Lee, Mark C. (Inventor); Kendall, Jr., James M. (Inventor)

1987-01-01

Improved, heterogeneous, refractory catalysts are in the form of gas-impervious, hollow, thin-walled spheres (10) suitable formed of a shell (12) of refractory such as alumina having a cavity (14) containing a gas at a pressure greater than atmospheric pressure. The wall material may be itself catalytic or a catalytically active material coated onto the sphere as a layer (16), suitably platinum or iron, which may be further coated with a layer (18) of activator or promoter. The density of the spheres (30) can be uniformly controlled to a preselected value within .+-.10 percent of the density of the fluid reactant such that the spheres either remain suspended or slowly fall or rise through the liquid reactant.

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.

Outcome of children with relapsed or refractory neuroblastoma: A meta-analysis of ITCC/SIOPEN European phase II clinical trials.

PubMed

Moreno, Lucas; Rubie, Herve; Varo, Amalia; Le Deley, Marie Cecile; Amoroso, Loredana; Chevance, Aurelie; Garaventa, Alberto; Gambart, Marion; Bautista, Francisco; Valteau-Couanet, Dominique; Geoerger, Birgit; Vassal, Gilles; Paoletti, Xavier; Pearson, Andrew D J

2017-01-01

Few randomized trials have been conducted in children with relapsed/refractory neuroblastoma and data about outcomes including progression-free survival (PFS) in these patients are scarce. A meta-analysis of three phase II studies of children with relapsed/refractory neuroblastoma conducted in Europe (temozolomide, topotecan-vincristine-doxorubicin and topotecan-temozolomide) was performed. Individual patient data with extended follow-up were collected from the trial databases after publication to describe trial outcomes (response rate, clinical benefit ratio, duration of treatment, PFS, and overall survival [OS]). Characteristics of subjects with relapsed/refractory neuroblastoma were compared. Data from 71 children and adolescents with relapsed/refractory neuroblastoma were collected. Response definitions were not homogeneous in the three trials. Patients were on study for a median of 3.5 months (interquartile range [IQR] 1.9-6.2). Of those, 35.2% achieved a complete or partial response, 26.3% experienced a response after more than two cycles, and 23.9% received more than six cycles. Median PFS from study entry for all, refractory, and relapsed patients was 6.4 ± 1.0, 12.5 ± 6.8, and 5.7 ± 1.0 months, respectively (P = 0.006). Median OS from study entry for all, refractory, and relapsed patients was 16.1 ± 4.3, 27.9 ± 20.2, and 11.0 ± 1.6 months, respectively (P = 0.03). Baseline data for response rate, clinical benefit ratio, duration of treatment, PFS, and OS were provided. Two subpopulations (relapsed/refractory) were clearly distinct and should be included in the interpretation of all trials. These results should help informing the design of forthcoming studies in relapsed/refractory neuroblastoma. © 2016 Wiley Periodicals, Inc.

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.

Low-Chrome/Chrome Free Refractories for Slagging Gasifiers

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

Bennett, J.P.; Kwong, K.-S.; Powell, C.P.

2007-01-01

Gasifiers are containment vessels used to react carbon-containing materials with oxygen and water, producing syngas (CO and H2) that is used in chemical and power production. It is also a potential source of H2 in a future hydrogen economy. Air cooled slagging gasifiers are one type of gasifier, operating at temperatures from 1275-1575º C and at pressures of 400 psi or higher. They typically use coal or petroleum coke as the carbon source, materials which contain ash impurities that liquefy at the gasification temperatures, producing liquid slag in quantities of 100 or more tons/day, depending on the carbon fed ratemore » and the percent ash present in the feedstock. The molten slag is corrosive to refractory linings, causing chemical dissolution and spalling. The refractory lining is composed of chrome oxide, alumina, and zirconia; and is replaced every 3-24 months. Gasifier users would like greater on-line availability and reliability of gasifier liners, something that has impacted gasifier acceptance by industry. Research is underway at NETL to improve refractory service life and to develop a no-chrome or low-chrome oxide alternative refractory liner. Over 250 samples of no- or low-chrome oxide compositions have been evaluated for slag interactions by cup testing; with potential candidates for further studies including those with ZrO2, Al2O3, and MgO materials. The development of improved liner materials is necessary if technologies such as IGCC and DOE’s Near Zero Emissions Advanced Fossil Fuel Power Plant are to be successful and move forward in the marketplace.« less

Alternating Bi-Weekly Intravitreal Ranibizumab and Bevacizumab for Refractory Neovascular Age-Related Macular Degeneration with Pigment Epithelial Detachment.

PubMed

Witkin, Andre J; Rayess, Nadim; Garg, Sunir J; Maguire, Joseph I; Storey, Philip; Kaiser, Richard S; Hsu, Jason; Vander, James F; Ho, Allen C

2017-01-01

To describe visual and anatomical outcomes following bi-weekly intravitreal ranibizumab/bevacizumab injections in eyes with refractory neovascular age-related macular degeneration (AMD) and pigment epithelial detachment (PED). Retrospective, consecutive, interventional case series. Eighteen patients diagnosed with neovascular AMD that were refractory to anti-VEGF therapy and received alternating biweekly ranibizumab/bevacizumab injections were included. Patients with neovascular AMD and PED that were refractory to at least 11 monthly ranibizumab or bevacizumab injections were included in this study at a large, single retina practice. Following inclusion, patients received four bi-weekly alternating ranibizumab/bevacizumab intravitreal injections. After completing a course of four bi-weekly injections, patients were treated with variable regimens of intravitreal anti-vascular endothelial growth factor (VEGF) therapy. The primary outcomes of the study included change in visual acuity (VA) and central foveal thickness (CFT) at eight weeks follow-up. Study eyes had previously received a mean of 22 intravitreal anti-VEGF injections. At enrollment, mean VA was 20/95 and mean CFT was 455 µm. After four bi-weekly anti-VEGF injections, mean VA improved to 20/65 (p < 0.001), and mean CFT decreased to 387 µm (p = 0.029). In patients with PED, there was a mean 27.9% reduction in height (p = 0.046) at eight weeks' follow-up. Four injections of bi-weekly alternating ranibizumab/bevacizumab improved visual acuity and reduced macular thickness in a number of patients with refractory neovascular AMD and PED.

Mitomycin-C: 'a ray of hope' in refractory corrosive esophageal strictures.

PubMed

Nagaich, N; Nijhawan, S; Katiyar, P; Sharma, R; Rathore, M

2014-04-01

Increasingly frequent dilation may become a self-defeating cycle in refractory stricture as recurrent trauma enhance, scar formation, and ultimately recurrence and potential worsening of the stricture. In 12 patients of caustic induced esophageal stricture, who failed to respond despite rigorous dilatation regimen for more than one year, a trial of topical mitomycin-C application to improve dilatation results was undertaken, considering the recently reported efficacy and safety of this agent. Mitomycin-C was applied for 2-3 minutes at the strictured esophageal segment after dilation with wire-guided Savary-Gilliard dilator. Patient was kept nil by mouth for 2-3 hours. After 4-6 sessions of mitomycin-C treatment, resolution of symptoms and significant improvement in dysphagia score and periodic dilatation index was seen in all 12 patients. Mitomycin-C topical application may be a useful strategy in refractory corrosive esophageal strictures and salvage patients from surgery. © 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Alkaline sulfide pretreatment of an antimonial refractory Au-Ag ore for improved cyanidation

NASA Astrophysics Data System (ADS)

Alp, Ibrahim; Celep, Oktay; Deveci, Haci

2010-11-01

This paper presents the alkaline sulfide pretreatment of an antimonial refractory gold and silver ore. In the ore, gold occurs mainly as gold-silver alloys and as associated with quartz and framboidal pyrite grains, and, to a small extent, as the inclusions within antimonial sulfides. Silver is present extensively as antimonial sulfides such as andorite. Alkaline sulfide pretreatment was shown to allow the decomposition of the antimonial sulfide minerals (up to 98% Sb removal) and to remarkably improve the amenability of gold (e.g., from <49% up to 83%) and silver (e.g., from <18% up to 90%) to subsequent cyanide leaching. An increase in reagent concentration (1-4 mol/L Na2S or NaOH) and temperature (20-80°C), and a decrease in particle size seem to produce an enhancing effect on metal extraction. These findings suggest that alkaline sulfide leaching can be suitably used as a chemical pretreatment method prior to the conventional cyanidation for antimonial refractory gold and silver ores.

Methods of use of calcium hexa aluminate refractory linings and/or chemical barriers in high alkali or alkaline environments

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

McGowan, Kenneth A; Cullen, Robert M; Keiser, James R

A method for improving the insulating character/and or penetration resistance of a liner in contact with at least one of an alkali and/or alkaline environments is provided. The method comprises lining a surface that is subject to wear by an alkali environment and/or an alkaline environment with a refractory composition comprising a refractory aggregate consisting essentially of a calcium hexa aluminate clinker having the formula CA.sub.6, wherein C is equal to calcium oxide, wherein A is equal to aluminum oxide, and wherein the hexa aluminate clinker has from zero to less than about fifty weight percent C.sub.12A.sub.7, and wherein greatermore » than 98 weight percent of the calcium hexa aluminate clinker having a particle size ranging from -20 microns to +3 millimeters, for forming a liner of the surface. This method improves the insulating character/and or penetration resistance of the liner.« less

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

PubMed Central

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

2007-01-01

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

A study of novel bilateral thermal capsulotomy with focused ultrasound for treatment-refractory obsessive-compulsive disorder: 2-year follow-up.

PubMed

Kim, Se Joo; Roh, Daeyoung; Jung, Hyun Ho; Chang, Won Seok; Kim, Chan-Hyung; Chang, Jin Woo

2018-05-02

Recently, a new thermal lesioning approach using magnetic-resonance-guided focused ultrasound (MRgFUS) was introduced for the treatment of neurologic disorders. However, only 2 studies have used this approach for treatment-refractory obsessive-compulsive disorder (OCD), and follow-up was short-term. We investigated the efficacy and safety of bilateral thermal lesioning of the anterior limb of the internal capsule using MRgFUS in patients with treatment-refractory OCD and followed them for 2 years. Eleven patients with treatment-refractory OCD were included in the study. Clinical outcomes were evaluated using the Yale-Brown Obsessive Compulsive Scale, the Clinical Global Impression scale (including improvement and severity), the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A) at 1 week and 1, 3, 6, 12 and 24 months following MRgFUS. Neuropsychological functioning, Global Assessment of Functioning and adverse events were also assessed. After MRgFUS, Yale-Brown Obsessive Compulsive Scale scores decreased significantly across the 24-month follow-up period (mean ± standard deviation, 34.4 ± 2.3 at baseline v. 21.3 ± 6.2 at 24 months, p < 0.001). Scores on the Hamilton rating scales for depression and anxiety also significantly decreased from baseline to 24 months (HAM-D, 19.0 ± 5.3 v. 7.6 ± 5.3, p < 0.001; HAM-A, 22.4 ± 5.9 v. 7.9 ± 3.9, p < 0.001). Global Assessment of Functioning scores improved significantly (35.8 ± 4.9 at baseline v. 56.0 ± 10.3 at 24 months, p < 0.001) and Memory Quotient significantly improved, but other neuropsychological functions were unchanged. The side effects of MRgFUS included headache and vestibular symptoms, but these were mild and transient. The main limitations of this study were the small sample size and the open-label design. Bilateral thermal lesioning of the anterior limb of the internal capsule using MRgFUS may improve obsessive-compulsive, depressive and anxiety symptoms in patients with treatment-refractory OCD, without serious adverse effects.

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.

Refractory gastro-oesophageal reflux disease: diagnosis and management.

PubMed

Liu, Julia J; Saltzman, John R

2009-10-01

Refractory gastro-oesophageal reflux disease (GORD) is described when reflux symptoms have not responded to 4-8 weeks of proton pump inhibitor therapy and occurs in a heterogeneous mixture of patients. The causes of refractory GORD include inadequate acid suppression, non-acid gastro-oesophageal reflux, and non-reflux causes of GORD symptoms including achalasia, gastroparesis and functional heartburn. Upper gastrointestinal tract endoscopy should initially be performed to identify the presence of oesophagitis, and exclude other diagnoses including eosinophilic oesophagitis and peptic ulcer disease. Patients with refractory symptoms but with a normal upper endoscopy are more difficult to diagnose and may require ambulatory pH monitoring, impedance testing, oesophageal motility tests and gastric emptying scans. The primary goal of treatment is symptom reduction and eventual elimination, which can be achieved with proper identification of the underlying cause of the symptoms.

Cross refractoriness between sodium metabisulphite and exercise induced asthma.

PubMed Central

Pavord, I.; Lazarowicz, H.; Inchley, D.; Baldwin, D.; Knox, A.; Tattersfield, A.

1994-01-01

BACKGROUND--Exercise and inhaled sodium metabisulphite are thought to cause bronchoconstriction in asthma through different mechanisms. The response to both stimuli becomes refractory with repeat challenge. The mechanism of refractoriness is unclear, although depletion of mast cell derived mediators or neurotransmitters has been suggested. Recent studies suggest a common mechanism involving release of inhibitory prostaglandins. If this is true, exercise and sodium metabisulphite induced bronchoconstriction should show cross refractoriness. METHODS--Thirteen subjects with mild asthma and previously established exercise and sodium metabisulphite induced bronchoconstriction performed two sodium metabisulphite challenges (giving a single dose previously shown to cause a 20% fall in FEV1) on one study day, and two exercise tests on another. The second challenge proceeded after recovery (FEV1 > 95% baseline) from the first. Subjects then attended on two further occasions when an exercise test was performed after sodium metabisulphite and a sodium metabisulphite challenge after exercise. RESULTS--When expressed as the percentage reduction in the area under the change in percentage FEV1 curve over 20 minutes (AUC) the response to exercise was reduced by a mean 62.3% (95% CI 46.5% to 78.1%) following a first exercise challenge, and by 50.7% (95% CI 27.8% to 73.6%) following a sodium metabisulphite challenge. The response to a sodium metabisulphite challenge was reduced by a mean of 80.2% (95% CI 68.9% to 91.5%) when it followed a sodium metabisulphite challenge, and by 37.3% (95% CI 15.1% to 59.5%) following an exercise challenge. CONCLUSION--This study shows some cross refractoriness between exercise and sodium metabisulphite induced bronchoconstriction, in keeping with a partially shared mechanism of refractoriness. PMID:8202881

Improvement in symptoms of the syndrome of mitochondrial encephalopathy, lactic acidosis, and stroke-like symptoms (MELAS) following treatment with sympathomimetic amines--possible implications for improving fecundity in women of advanced reproductive age.

PubMed

Potestio, C P; Check, J H; Mitchell-Williams, J

2014-01-01

To evaluate the efficacy of sympathomimetic amine therapy on a mitochondrial abnormality known as the mitochondrial encephalopathy lactic acidosis and stroke-like symptoms syndrome (MELAS syndrome). Dextroamphetamine sulfate 15 mg extended release capsule was prescribed to a woman with a 25 year history of MELAS syndrome refractory to most other therapies. Within one month of therapy the woman noticed considerable improvement in her chronic fatigue, pain, and edema. The MELAS syndrome is thus another condition to add to the list of various chronic refractory disorders that improve considerably after dextroamphetamine therapy. This is the first mitochondrial disorder shown to improve with sympathomimetic amines which could suggest that dextroamphetamine could prove useful in decreasing the risk of aneuploidy in women of advanced reproductive age.

Distributed Fiber Optic Sensor for On-Line Monitoring of Coal Gasifier Refractory Health

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

Wang, Anbo; Yu, Zhihao

This report summarizes technical progress on the program “Distributed Fiber Optic Sensor for On-Line Monitoring of Coal Gasifier Refractory Health,” funded by the National Energy Technology Laboratory of the U.S. Department of Energy, and performed by the Center for Photonics Technology of the Bradley Department of Electrical and Computer Engineering at Virginia Tech. The scope of work entails analyses of traveling grating generation technologies in an optical fiber, as well as the interrogation of the gratings to infer a distributed temperature along the fiber, for the purpose of developing a real-time refractory health condition monitoring technology for coal gasifiers. Duringmore » the project period, which is from 2011-2015, three different sensing principles were studied, including four-wave mixing (FWM), coherent optical time-domain reflectometer (C-OTDR) and Brillouin optical time-domain analysis (BOTDA). By comparing the three methods, the BOTDA was selected for further development into a complete bench-top sensing system for the proposed high-temperature sensing application. Based on the input from Eastman Chemical, the industrial collaborator on this project, a cylindrical furnace was designed and constructed to simulate typical gasifier refractory temperature conditions in the laboratory, and verify the sensor’s capability to fully monitor refractory conditions on the back-side at temperatures up to 1000°C. In the later stages of the project, the sensing system was tested in the simulated environment for its sensing performance and high-temperature survivability. Through theoretical analyses and experimental research on the different factors affecting the sensor performance, a sensor field deployment strategy was proposed for possible future sensor field implementations.« less

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

Effectiveness of intravenous levetiracetam as an adjunctive treatment in pediatric refractory status epilepticus.

PubMed

Kim, Jon Soo; Lee, Jeong Ho; Ryu, Hye Won; Lim, Byung Chan; Hwang, Hee; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Kim, Hunmin

2014-08-01

Intravenous levetiracetam (LEV) has been shown to be effective and safe in treating adults with refractory status epilepticus (SE). We sought to investigate the efficacy and safety of intravenous LEV for pediatric patients with refractory SE. We performed a retrospective medical-record review of pediatric patients who were treated with intravenous LEV for refractory SE. Clinical information regarding age, sex, seizure type, and underlying neurological status was collected. We evaluated other anticonvulsants that were used prior to administration of intravenous LEV and assessed loading dose, response to treatment, and any adverse events from intravenous LEV administration. Fourteen patients (8 boys and 6 girls) received intravenous LEV for the treatment of refractory SE. The mean age of the patients was 4.4 ± 5.5 years (range, 4 days to 14.6 years). Ten of the patients were neurologically healthy prior to the refractory SE, and the other 4 had been previously diagnosed with epilepsy. The mean loading dose of intravenous LEV was 26 ± 4.6 mg/kg (range, 20-30 mg/kg). Seizure termination occurred in 6 (43%) of the 14 patients. In particular, 4 (57%) of the 7 patients younger than 2 years showed seizure termination. No immediate adverse events occurred during or after infusions. The current study demonstrated that the adjunctive use of intravenous LEV was effective and well tolerated in pediatric patients with refractory SE, even in patients younger than 2 years. Intravenous LEV should be considered as an effective and safe treatment option for refractory SE in pediatric patients.

Microstructural Design for Improving Ductility of An Initially Brittle Refractory High Entropy Alloy.

PubMed

Soni, V; Senkov, O N; Gwalani, B; Miracle, D B; Banerjee, R

2018-06-11

Typically, refractory high-entropy alloys (RHEAs), comprising a two-phase ordered B2 + BCC microstructure, exhibit extraordinarily high yield strengths, but poor ductility at room temperature, limiting their engineering application. The poor ductility is attributed to the continuous matrix being the ordered B2 phase in these alloys. This paper presents a novel approach to microstructural engineering of RHEAs to form an "inverted" BCC + B2 microstructure with discrete B2 precipitates dispersed within a continuous BCC matrix, resulting in improved room temperature compressive ductility, while maintaining high yield strength at both room and elevated temperature.

Refractory orthostatic hypotension in a patient with a spinal cord injury: Treatment with droxidopa.

PubMed

Canosa-Hermida, Eva; Mondelo-García, Cristina; Ferreiro-Velasco, María Elena; Salvador-de la Barrera, Sebastián; Montoto-Marqués, Antonio; Rodríguez-Sotillo, Antonio; Vizoso-Hermida, José Ramón

2018-01-01

Orthostatic hypotension (OH) is a common complication in patients with a spinal cord injury, mainly affecting complete injuries above neurological level T6. It is generally more severe during the acute phase but can remain symptomatic for several years. A 65-year-old male with a grade ASIA A post-traumatic cervical spinal cord injury, at neurological level C4, presenting with symptomatic refractory OH. Increased blood pressure (BP) levels and an overall clinical improvement was observed after administering an increasing dose of droxidopa. Treatment was started at a dose of 100 mg twice daily (bid), one to be taken upon rising in the morning and another one in the afternoon, at least three hours before bedtime. According to the patient's symptomatic response, each individual dose was increased by 100 mg at 48-hour intervals. Both increased mean BP levels and a subjective symptomatic improvement were evidenced at a dose of 300 mg bid. Treatment with droxidopa increases BP levels and improves symptoms related to refractory OH using all physical and pharmacological measures available. It could therefore constitute an effective alternative treatment for OH in patients with a spinal cord injury.

Autologous hematopoietic stem cells for refractory Crohn's disease.

PubMed

DiNicola, C A; Zand, A; Hommes, D W

2017-05-01

Autologous hematopoietic stem cells are gaining ground as an effective and safe treatment for treating severe refractory Crohn's disease (CD). Autologous hematopoietic stem cell therapy (AHSCT) induces resetting of the immune system by de novo regeneration of T-cell repertoire and repopulation of epithelial cells by bone-marrow derived cells to help patients achieve clinical and endoscopic remission. Areas covered: Herein, the authors discuss the use of AHSCT in treating patients with CD. Improvements in disease activity have been seen in patients with severe autoimmune disease and patients with severe CD who underwent AHSCT for a concomitant malignant hematological disease. Clinical and endoscopic remission has been achieved in patients treated with AHSCT for CD. The only randomized trial published to date, the ASTIC Trial, did not support further use of AHSCT to treat CD. Yet, critics of this trial have deemed AHSCT as a promising treatment for severe refractory CD. Expert opinion: Even with the promising evidence presented for HSCT for refractory CD, protocols need to be refined through the collaboration of GI and hemato-oncology professionals. The goal is to incorporate safe AHSCT and restore tolerance by delivering an effective immune 'cease fire' as a treatment option for severe refractory CD.

MRI-negative refractory partial epilepsy: role for diffusion tensor imaging in high field MRI.

PubMed

Chen, Qin; Lui, Su; Li, Chun-Xiao; Jiang, Li-Jun; Ou-Yang, Luo; Tang, He-Han; Shang, Hui-Fang; Huang, Xiao-Qi; Gong, Qi-Yong; Zhou, Dong

2008-07-01

Our aim is to use the high field MR scanner (3T) to verify whether diffusion tensor imaging (DTI) could help in locating the epileptogenic zone in patients with MRI-negative refractory partial epilepsy. Fifteen patients with refractory partial epilepsy who had normal conventional MRI, and 40 healthy volunteers were recruited for the study. DTI was performed on a 3T MR scanner, individual maps of mean diffusivity (MD) and fractional anisotropy (FA) were calculated, and Voxel-Based Analysis (VBA) was performed for individual comparison between patients and controls. Voxel-based analysis revealed significant MD increase in variant regions in 13 patients. The electroclinical seizure localization was concurred to seven patients. No patient exhibited regions of significant decreased MD. Regions of significant reduced FA were observed in five patients, with two of these concurring with electroclinical seizure localization. Two patients had regions of significant increase in FA, which were distinct from electroclinical seizure localization. Our study's results revealed that DTI is a responsive neuroradiologic technique that provides information about the epileptogenic areas in patients with MRI-negative refractory partial epilepsy. This technique may also helpful in pre-surgical evaluation.

Using preoperative unsupervised cluster analysis of chronic rhinosinusitis to inform patient decision and endoscopic sinus surgery outcome.

PubMed

Adnane, Choaib; Adouly, Taoufik; Khallouk, Amine; Rouadi, Sami; Abada, Redallah; Roubal, Mohamed; Mahtar, Mohamed

2017-02-01

The purpose of this study is to use unsupervised cluster methodology to identify phenotype and mucosal eosinophilia endotype subgroups of patients with medical refractory chronic rhinosinusitis (CRS), and evaluate the difference in quality of life (QOL) outcomes after endoscopic sinus surgery (ESS) between these clusters for better surgical case selection. A prospective cohort study included 131 patients with medical refractory CRS who elected ESS. The Sino-Nasal Outcome Test (SNOT-22) was used to evaluate QOL before and 12 months after surgery. Unsupervised two-step clustering method was performed. One hundred and thirteen subjects were retained in this study: 46 patients with CRS without nasal polyps and 67 patients with nasal polyps. Nasal polyps, gender, mucosal eosinophilia profile, and prior sinus surgery were the most discriminating factors in the generated clusters. Three clusters were identified. A significant clinical improvement was observed in all clusters 12 months after surgery with a reduction of SNOT-22 scores. There was a significant difference in QOL outcomes between clusters; cluster 1 had the worst QOL improvement after FESS in comparison with the other clusters 2 and 3. All patients in cluster 1 presented CRSwNP with the highest mucosal eosinophilia endotype. Clustering method is able to classify CRS phenotypes and endotypes with different associated surgical outcomes.

Current and future perspectives in the management of gastroesophageal reflux disease.

PubMed

Akiyama, Junichi; Kuribayashi, Shiko; Baeg, Myong Ki; de Bortoli, Nicola; Valitova, Elen; Savarino, Edoardo V; Kusano, Motoyasu; Triadafilopoulos, George

2018-05-16

Although the prevalence of gastroesophageal reflux disease (GERD) used to be lower in East Asia as compared to Western countries, it has recently been increasing, most likely due to the socioeconomic development in the East. The prevalence of both GERD and functional gastrointestinal disorders (FGIDs) ranges between 10% and 25% worldwide and there are distinct subgroups of patients with overlapping of GERD and FGIDs. However, the true prevalence of an overlap between GERD and FGIDs can be determined only when a formal pathophysiological evaluation has been performed. Nocturnal reflux symptoms have a significant impact on patients' sleep quality and quality of life. Although proton pump inhibitors (PPIs) can improve both reflux and sleep-related symptoms, the relationship between nocturnal reflux events and sleep disturbance is not fully understood. GERD plays an important role in the pathogenesis of lung fibrosis, and PPIs or fundoplication may decrease the likelihood of pulmonary exacerbation or even improve pulmonary function. Refractory reflux symptoms without esophagitis have become one of the most common presentations of GERD in gastroenterology clinics. There are several new medical therapies, and endoscopic as well as laparoscopic techniques that have been increasingly used in these patients. The selection of options should be tailored and individualized based on the pathophysiology of refractory GERD. © 2018 New York Academy of Sciences.

Refractory chronic migraine: is drug withdrawal necessary before starting a therapy with onabotulinum toxin type A?

PubMed

Butera, Calogera; Colombo, Bruno; Bianchi, Francesca; Cursi, Marco; Messina, Roberta; Amadio, Stefano; Guerriero, Roberta; Comi, Giancarlo; Del Carro, Ubaldo

2016-10-01

Onabotulinum toxin A (BT-A) is now one of the authorized prophylaxis treatments for chronic migraine (CM) thanks to previous clinical trials, which usually required a pharmacologic washout as a precondition for demonstrating its efficacy. Aim of our study was to assess the efficacy in daily clinical practice of BT-A injections in refractory CM patients, regardless of medication overuse without any standardized withdrawal protocol and without stopping the ongoing prophylaxis treatment as well. We treated 44 refractory CM patients (37 females and 7 males) trimonthly without any modification in symptomatic, or prophylactic drug therapy. Main efficacy variables included number of headache, or migraine days and episodes, total cumulative headache hours, MIDAS and HIT-6 scores; all items were assessed at baseline and at the 12-, 24-, and 36-week follow-up. All variables showed a statistically significant improvement at week 36. In general, more than 50 % of patients had a good clinical outcome (including all improved patients, either partial or full responder) and that the percentage of drug abuser patients significantly decreased from 75 to 50 %, thanks to a spontaneous reduction of the symptomatic drug intake. Adverse events were uncommon and did not require treatment discontinuation. Onabotulinum toxin A treatment in refractory CM patients with unsatisfactory prophylactic drug treatments and pharmacological abuse is effective in improving clinical outcome and quality of life. This result may be achieved through a flexible pharmacologic approach tailored to each patient's needs; moreover, the patient himself can be often expected to reduce drug consumption spontaneously.

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.

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.

Long-term efficacy of anti-CD20 antibodies in refractory lupus nephritis.

PubMed

Arce-Salinas, C Alejandro; Rodríguez-García, Felipe; Gómez-Vargas, J Iván

2012-05-01

Eight patients with refractory lupus nephritis received rituximab after failing standard sequential therapy and were followed for 104 weeks after the infusion. One patient died secondary to a complicated pregnancy but had stable renal function. Three patients received a re-infusion of rituximab approximately 12 months apart due to a renal flare; during the second year of follow-up, those patients progressed toward ESRD. The four remaining patients demonstrated improvements in SLEDAI score, CrCl, and proteinuria with maintenance of their standard immunosuppressive therapy and did not require a re-infusion of rituximab. Although rituximab as induction therapy for refractory lupus nephritis has been shown to have a good response, its efficacy in long-term assessments demonstrates disappointing results.

The ketogenic diet in two paediatric patients with refractory myoclonic status epilepticus.

PubMed

Caraballo, Roberto Horacio; Valenzuela, Gabriela Reyes; Armeno, Marisa; Fortini, Sebastian; Mestre, Graciela; Cresta, Araceli

2015-12-01

We describe two patients with refractory myoclonic status epilepticus treated with the ketogenic diet. Between May 1, 2014 and January 1, 2015, two patients who met the diagnostic criteria for refractory myoclonic status epilepticus, seen at our department, were placed on the ketogenic diet and followed for a minimum of six months. One patient with myoclonic epilepsy of unknown aetiology had a 75-90% seizure reduction, and the other with progressive encephalopathy associated with myoclonic epilepsy had a 50% seizure reduction. Both patients retained good tolerability for the diet. At the last control, one patient had isolated myoclonias and EEG showed occasional generalized spike-and-polyspike waves; the patient is now successfully attending kindergarten. The quality of life of the second patient improved significantly. In both cases, the number of antiepileptic drugs was reduced. The ketogenic diet is an effective and well-tolerated treatment option for patients with refractory myoclonic status epilepticus and should be considered earlier in the course of treatment.

Long-term complete remission with belinostat in a patient with chemotherapy refractory peripheral T-cell lymphoma.

PubMed

Reimer, Peter; Chawla, Shanta

2013-09-10

Peripheral T/NK-cell lymphomas (PTCL) are rare malignancies with a poor prognosis. Due to the lack of randomised studies, standard therapy has not been established. First-line treatment with anthracycline-based polychemotherapy followed by consolidation with high-dose therapy and autologous stem cell transplant in responding patients has demonstrated good feasibility with low toxicity in prospective studies and is widely used in eligible patients. In relapsed and refractory patients, who are not candidates for transplant approaches, therapeutic options are limited and are usually palliative. Several new agents are currently under investigation to improve the outcome of PTCL in the first line and salvage settings. Belinostat, a histone deacetylase (HDAC) inhibitor, has demonstrated broad antineoplastic activity in preclinical studies, and promising results in advanced relapsed/refractory lymphomas.Here, we report the case of a 73 year old patient with heavily pre-treated refractory PTCL in complete remission with belinostat for 39 months.

Intraarticular Pulsed Radiofrequency to Treat Refractory Lumbar Facet Joint Pain in Patients with Low Back Pain.

PubMed

Chang, Min Cheol; Cho, Yun-Woo; Ahn, Da Hyun; Do, Kyung Hee

2018-04-01

Many treatment techniques have been used for refractory lumbar facet joint pain; however, their efficacy has been controversial. In this study, we investigated the clinical efficacy and safety of intra-articular pulsed radiofrequency for the treatment of refractory lumbar facet joint pain in patients with low back pain. Twenty patients with refractory lumbar facet joint pain were recruited, and each patient was treated via intra-articular pulsed radiofrequency. The treatment effects were measured with a numerical rating scale, and the technical accuracy of intra-articular pulsed radiofrequency treatment was evaluated independently by 2 radiologists. Any adverse events or complications also were checked. We performed intra-articular pulsed radiofrequency treatment at 48 levels of the lumbar facet joints in 20 patients (5 men and 15 women; mean age, 64.50 ± 10.65 years) with refractory lumbar facet joint pain. Pain scores were significantly reduced at 1 month, 3 months, and 6 months after treatment (P < 0.05). The face validity revealed good intraarticular pulsed radiofrequency results in all 20 patients, without any serious adverse effects. Treatment using intra-articular pulsed radiofrequency is an alternative to other techniques in patients with refractory lumbar facet joint pain. Copyright © 2018 Elsevier Inc. All rights reserved.

Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center.

PubMed

Benhamou, Y; Boelle, P-Y; Baudin, B; Ederhy, S; Gras, J; Galicier, L; Azoulay, E; Provôt, F; Maury, E; Pène, F; Mira, J-P; Wynckel, A; Presne, C; Poullin, P; Halimi, J-M; Delmas, Y; Kanouni, T; Seguin, A; Mousson, C; Servais, A; Bordessoule, D; Perez, P; Hamidou, M; Cohen, A; Veyradier, A; Coppo, P

2015-02-01

Cardiac involvement is a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed, owing to subclinical injuries. Cardiac troponin-I measurement (cTnI) on admission could improve the early diagnosis of cardiac involvement and have prognostic value. To assess the predictive value of cTnI in patients with TTP for death or refractoriness. The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS-13 deficiency (< 10%) and included in the registry of the French Reference Center for Thrombotic Microangiopathies. Centralized cTnI measurements were performed on frozen serum on admission. Between January 2003 and December 2011, 133 patients with TTP (mean age, 48 ± 17 years) had available cTnI measurements on admission. Thirty-two patients (24%) had clinical and/or electrocardiogram features. Nineteen (14.3%) had cardiac symptoms, mainly congestive heart failure and myocardial infarction. Electrocardiogram changes, mainly repolarization disorders, were present in 13 cases. An increased cTnI level (> 0.1 μg L(-1) ) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. The main outcomes were death (25%) and refractoriness (17%). Age (P = 0.02) and cTnI level (P = 0.002) showed the greatest impact on survival. A cTnI level of > 0.25 μg L(-1) was the only independent factor in predicting death (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.13-7.22; P = 0.024) and/or refractoriness (OR 3.03; 95% CI 1.27-7.3; P = 0.01). A CTnI level of > 0.25 μg L(-1) at presentation in patients with TTP appears to be an independent factor associated with a three-fold increase in the risk of death or refractoriness. Therefore, cTnI level should be considered as a prognostic indicator in patients diagnosed with TTP. © 2014 International Society on Thrombosis and Haemostasis.

Effectiveness of Thermal Annular Procedures in Treating Discogenic Low Back Pain.

PubMed

Helm Ii, Standiford; Simopoulos, Thomas T; Stojanovic, Milan; Abdi, Salahadin; El Terany, Mohamed Ahamed

2017-09-01

Discogenic low back is a distinct clinic entity characterized by pain arising from a damaged disc. The diagnosis is clouded by the controversy surrounding discography. The treatment options are limited, with unsatisfactory results from both conservative treatment and surgery. Multiple interventional therapies have been developed to treat discogenic pain, but most have not yet been validated by high quality studies.The best studied treatment for discogenic pain is the use of heat, which has been labeled as thermal intradiscal procedures (TIPs) by the Centers for Medicare and Medicaid Services (CMS). As the pathology is located in the annulus, we use the term thermal annular procedures (TAPs). The aim of this study is to evaluate and update the efficacy of TAPs to treat chronic refractory discogenic pain. The design of this study is a systematic review. The available literature on TAPs in treating chronic refractory discogenic pain was reviewed. The quality of each article used in this analysis was assessed.The level of evidence was classified on a 5-point scale from strong, based upon multiple randomized controlled trials (RCTs) to weak, based upon consensus, as developed by the US Preventive Services Task Force (USPSTF) and modified by the American Society of Interventional Pain Physicians (ASIPP).Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to September 2015 and manual searches of the bibliographies of known primary and review articles.The primary outcome measures were pain relief and functional improvement of at least 40%. Short-term efficacy was defined as improvement for less than 6 months; long-term efficacy was defined as improvement for 6 months or more. For this systematic review, 49 studies were identified. Of these, there were 4 RCTs and no observational studies which met the inclusion criteria. Based upon 2 RCTs showing efficacy, with no negative trials, there is Level I, or strong, evidence of the efficacy of biacuplasty in the treatment of chronic, refractory discogenic pain.Based upon one high-quality RCT showing efficacy and one moderate-quality RCT interpreted as showing no benefit, there is Level III, or moderate, evidence supporting the use of intradiscal electrothermal therapy (IDET) in treating chronic, refractory discogenic pain.The evidence supporting the use of discTRODE is level V, or limited. The evidence is Level I, or strong, that percutaneous biacuplasty is efficacious in the treatment of chronic, refractory discogenic pain. Biacuplasty may be considered as a first-line treatment for chronic, refractory discogenic pain.The evidence is Level III, or moderate, that IDET is efficacious in the treatment of chronic, refractory discogenic pain.The evidence is Level V, or limited, that discTRODE is efficacious in the treatment of chronic, refractory discogenic pain.Key words: Spinal pain, chronic low back pain, intradiscal disorder, IDET, biacuplasty, discTRODE, thermal intradiscal disorders, thermal annular disorders.

The Results of the Use of Ahmed Valve in Refractory Glaucoma Surgery

PubMed Central

Bikbov, Mukharram Mukhtaramovich

2015-01-01

ABSTRACT The treatment of refractory glaucoma (RG) is challenging. The commonly adopted strategy in RG treatment is a glaucoma drainage device (GDD) implantation, which despite its radical nature may not always provide the desired intraocular pressure (IOP) levels for a long term. This review is based on the scientific literature on Ahmed glaucoma valve (AGV) implantation for refractory glaucoma. The technique of AGV implantation is described and data for both the types, FP7 and FP8 performance are presented. The outcome with adjunct antimetabolite and anti-VEGF drugs are also highlighted. An insight is given about experimental and histological examinations of the filtering bleb encapsulation. The article also describes various complications and measures to prevent them. How to cite this article: Bikbov MM, Khusnitdinov II. The Results of the Use of Ahmed Valve in Refractory Glaucoma Surgery. J Curr Glaucoma Pract 2015;9(3):86-91. PMID:26997843

Effect of spinal cord stimulation on myocardial perfusion reserve in patients with refractory angina pectoris.

PubMed

Saraste, Antti; Ukkonen, Heikki; Varis, Antti; Vasankari, Tuija; Tunturi, Satu; Taittonen, Markku; Rautakorpi, Pirkka; Luotolahti, Matti; Airaksinen, K E Juhani; Knuuti, Juhani

2015-04-01

Epidural spinal cord stimulation (SCS) provides symptom relief in refractory angina pectoris, but its mechanism of action remains incompletely understood. We studied effects of short-term SCS therapy on myocardial ischaemia tolerance, myocardial perfusion reserve (MPR), and endothelium-mediated vasodilatation induced by cold pressor test (CPT) in patients with refractory angina pectoris. We prospectively recruited 18 patients with refractory angina pectoris and studied them after implantation of SCS device at baseline before starting the therapy and after 3 weeks of continuous SCS therapy. Myocardial ischaemia was evaluated by dobutamine stress echocardiography. Global and regional myocardial blood flow (MBF) were measured using positron emission tomography and (15)O-water at rest, during adenosine stress, and in response to CPT. Systemic haemodynamics were comparable before and after 3 weeks of SCS at rest, during adenosine stress and during CPT. Appearance of angina pectoris induced by dobutamine stress was delayed after SCS therapy. Global MPR increased (P = 0.02) from 1.7 ± 0.6 at baseline to 2.0 ± 0.6 after 3-week SCS therapy. This was associated with a significant reduction in global MBF at rest and increase in MBF induced by adenosine in the ischaemic regions. Global MBF response to CPT was improved after SCS (0.27 ± 0.20 vs. 0.40 ± 0.15, P = 0.03). Short-term SCS therapy improved myocardial ischaemia tolerance, absolute MPR, and endothelium-mediated vasomotor function in refractory angina pectoris, indicating that this therapy can alleviate myocardial perfusion abnormalities in advanced CAD. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Transcutaneous stimulation of the posterior tibial nerve for treating refractory urge incontinence of idiopathic and neurogenic origin.

PubMed

Valles-Antuña, C; Pérez-Haro, M L; González-Ruiz de L, C; Quintás-Blanco, A; Tamargo-Diaz, E M; García-Rodríguez, J; San Martín-Blanco, A; Fernandez-Gomez, J M

2017-09-01

To assess the efficacy of treatment with transcutaneous posterior tibial nerve stimulation (TPTNS) in patients with urge urinary incontinence, of neurogenic or nonneurogenic origin, refractory to first-line therapeutic options. We included 65 patients with urge urinary incontinence refractory to medical treatment. A case history review, a urodynamic study and a somatosensory evoked potentials (SEP) study were conducted before the TPTNS, studying the functional urological condition by means of a voiding diary. The treatment consisted of 10 weekly sessions of TPTNS lasting 30minutes. Some 57.7% of the patients showed abnormal tibial SEPs, and 42% showed abnormal pudendal SEPs. A statistically significant symptomatic improvement was observed in all clinical parameters after treatment with TPTNS, and 66% of the patients showed an overall improvement, regardless of sex, the presence of underlying neurological disorders, detrusor hyperactivity in the urodynamic study or SEP disorders. There were no adverse effects during the treatment. TPTNS is an effective and well tolerated treatment in patients with urge incontinence refractory to first-line therapies and should be offered early in the treatment strategy. New studies are needed to identify the optimal parameters of stimulation, the most effective treatment protocols and long-term efficacy, as well as its applicability to patients with a neurogenic substrate. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Hyperbaric oxygen therapy stimulates colonic stem cells and induces mucosal healing in patients with refractory ulcerative colitis: a prospective case series

PubMed Central

Bekheit, Mohamed; Baddour, Nahed; Katri, Khaled; Taher, Yousry; El Tobgy, Khaled; Mousa, Essam

2016-01-01

Background Hyperbaric oxygen (HBO) is used as part of treatment in a variety of clinical conditions. Its use in the treatment of ulcerative colitis has been reported in few clinical reports. Objective We report the effect of HBO on refractory ulcerative colitis exploring one potential mechanism of action. Design A review of records of patients with refractory ulcerative colitis who received HBO was conducted. Clinical and histopathological scoring was utilised to evaluate the response to HBO therapy (HBOT). Results All patients manifested clinical improvement by the 40th cycle of HBOT. The median number of stool frequency dropped from seven motions/day (range=3–20) to 1/day (range=0.5–3), which was significant (z=−4.6, p<0.001). None of the patients manifested persistent blood passage after HBOT (z=−3.2, p=0.002). The severity index significantly improved after HBOT (z=−4.97, p<0.001). Histologically, a significant reduction of the scores of activity was recorded accompanied by a significant increase in the proliferating cell nuclear antigen labelling index of the CD44 cells of the colonic mucosa (p=0.001). Conclusions HBOT is effective in the setting of refractory ulcerative colitis. The described protocol is necessary for successful treatment. HBOT stimulates colonic stem cells to promote healing. PMID:27195128

New-onset refractory status epilepticus

PubMed Central

Foreman, Brandon P.; Alvarez, Vincent; Cabrera Kang, Christian; Probasco, John C.; Jongeling, Amy C.; Meyers, Emma; Espinera, Alyssa; Haas, Kevin F.; Schmitt, Sarah E.; Gerard, Elizabeth E.; Gofton, Teneille; Kaplan, Peter W.; Lee, Jong W.; Legros, Benjamin; Szaflarski, Jerzy P.; Westover, Brandon M.; LaRoche, Suzette M.; Hirsch, Lawrence J.

2015-01-01

Objectives: The aims of this study were to determine the etiology, clinical features, and predictors of outcome of new-onset refractory status epilepticus. Methods: Retrospective review of patients with refractory status epilepticus without etiology identified within 48 hours of admission between January 1, 2008, and December 31, 2013, in 13 academic medical centers. The primary outcome measure was poor functional outcome at discharge (defined as a score >3 on the modified Rankin Scale). Results: Of 130 cases, 67 (52%) remained cryptogenic. The most common identified etiologies were autoimmune (19%) and paraneoplastic (18%) encephalitis. Full data were available in 125 cases (62 cryptogenic). Poor outcome occurred in 77 of 125 cases (62%), and 28 (22%) died. Predictors of poor outcome included duration of status epilepticus, use of anesthetics, and medical complications. Among the 63 patients with available follow-up data (median 9 months), functional status improved in 36 (57%); 79% had good or fair outcome at last follow-up, but epilepsy developed in 37% with most survivors (92%) remaining on antiseizure medications. Immune therapies were used less frequently in cryptogenic cases, despite a comparable prevalence of inflammatory CSF changes. Conclusions: Autoimmune encephalitis is the most commonly identified cause of new-onset refractory status epilepticus, but half remain cryptogenic. Outcome at discharge is poor but improves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune therapies warrants further investigation. PMID:26296517

A Nationwide Survey About Palliative Sedation Involving Japanese Palliative Care Specialists: Intentions and Key Factors Used to Determine Sedation as Proportionally Appropriate.

PubMed

Hamano, Jun; Morita, Tatsuya; Ikenaga, Masayuki; Abo, Hirofumi; Kizawa, Yoshiyuki; Tunetou, Satoru

2018-03-01

Although there has long been debate about physicians' intentions and what physicians consider to be proportionally appropriate when performing palliative sedation, few large studies have been performed. To identify physicians' intentions when starting continuous deep sedation and to clarify what factors determine whether physicians regard sedation as proportionally appropriate in relation to expected survival, the patients' wishes, and refractoriness. A nationwide questionnaire survey of Japanese palliative care specialists was performed from August to December 2016. We defined continuous deep sedation as the continuous use of sedatives to relieve intolerable and refractory symptoms with the loss of consciousness until death. Of the 695 palliative care specialists enrolled, 440 were analyzed (response rate, 69%). A total of 95% and 87% of the physicians reported that they explicitly intended to perform symptom palliation and decrease consciousness levels, respectively. Moreover, 38% answered that they explicitly intended to maintain unconsciousness until death, and 11% reported that they intended to shorten survival to some extent. The respondents considered that continuous deep sedation is more appropriate when the predicted survival is shorter, the patients' wishes are consistent and clear, and confidence in the refractoriness of symptoms is higher. Japanese palliative care specialists explicitly intend to control symptoms and reduce the level of consciousness when performing continuous deep sedation, but there are differences in their intentions with regard to maintaining unconsciousness until death. Predicted survival, patients' wishes, and confidence in refractoriness are associated with physicians' judgment that sedation is proportionally appropriate. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Joining of ceramics for high performance energy systems. Mid-term progress report, August 1, 1979-March 31, 1980

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

Smeltzer, C E; Metcalfe, A G

The subject program is primarily an exploratory and demonstration study of the use of silicate glass-based adhesives for bonding silicon-base refractory ceramics (SiC, Si/sub 3/N/sub 4/). The projected application is 1250 to 2050/sup 0/F relaxing joint service in high-performance energy conversion systems. The five program tasks and their current status are as follows. Task 1 - Long-Term Joint Stability. Time-temperature-transformation studies of candidate glass adhesives, out to 2000 hours simulated service exposure, are half complete. Task 2 - Environmental and Service Effects on Joint Reliability. Start up delayed due to late delivery of candidate glass fillers and ceramic specimens. Taskmore » 3 - Viscoelastic Damping of Glass Bonded Ceramics. Promising results obtained over approximately the same range of glass viscosity required for joint relaxation function (10/sup 7.5/ to 10/sup 9.5/ poise). Work is 90% complete. Task 4 - Crack Arrest and Crack Diversion by Joints. No work started due to late arrival of materials. Task 5 - Improved Joining and Fabrication Methods. Significant work has been conducted in the area of refractory pre-glazing and the application and bonding of high-density candidate glass fillers (by both hand-artisan and slip-spray techniques). Work is half complete.« less

Molecular Determinants of Hormone Refractory Prostate Cancer

DTIC Science & Technology

2017-07-01

Award Number: W81XWH-12-1-0062 TITLE: Molecular Determinants of Hormone Refractory Prostate Cancer PRINCIPAL INVESTIGATOR: Atish Choudhury...ABOVE ADDRESS. 1. REPORT DATE July 2017 2. REPORT TYPE Annual 3. DATES COVERED 1 July 2012 - 30 June 2017 4. TITLE AND SUBTITLE Molecular ...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT We have performed a high throughput, in vivo genetic screen to identify kinases that permit androgen

Ultrasound-guided platelet-rich plasma injection for distal biceps tendinopathy.

PubMed

Barker, Scott L; Bell, Simon N; Connell, David; Coghlan, Jennifer A

2015-04-01

Distal biceps tendinopathy is an uncommon cause of elbow pain. The optimum treatment for cases refractory to conservative treatment is unclear. Platelet-rich plasma has been used successfully for other tendinopathies around the elbow. Six patients with clinical and radiological evidence of distal biceps tendinopathy underwent ultrasound-guided platelet-rich plasma (PRP) injection. Clinical examination findings, visual analogue score (VAS) for pain and Mayo Elbow Performance scores were recorded. The Mayo Elbow Performance Score improved from 68.3 (range 65 to 85) (fair function) to 95 (range 85 to 100) (excellent function). The VAS at rest improved from a mean of 2.25 (range 2 to 5) pre-injection to 0. The VAS with movement improved from a mean of 7.25 (range 5 to 8) pre-injection to 1.3 (range 0 to 2). No complications were noted. Ultrasound-guided PRP injection appears to be a safe and effective treatment for recalcitrant cases of distal biceps tendinopathy. Further investigation with a randomized controlled trial is needed to fully assess its efficacy.

Accelerated Total Lymphoid Irradiation-containing Salvage Regimen for Patients With Refractory and Relapsed Hodgkin Lymphoma: 20 Years of Experience

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

Rimner, Andreas; Lovie, Shona; Hsu, Meier

Purpose: We report the long-term results of integrated accelerated involved field radiation therapy (IFRT) followed by total lymphoid irradiation (TLI) as part of the high-dose salvage regimen followed by autologous bone marrow transplantation or autologous stem cell transplantation in patients with relapsed or refractory Hodgkin lymphoma (HL). Methods and Materials: From November 1985 to July 2008, 186 previously unirradiated patients with relapsed or refractory HL underwent salvage therapy on 4 consecutive institutional review board–approved protocols. All patients had biopsy-proven primary refractory or relapsed HL. After standard-dose salvage chemotherapy (SC), accelerated IFRT (18-20 Gy) was given to relapsed or refractory sites, followedmore » by TLI (15-18 Gy) and high-dose chemotherapy. Overall survival (OS) and event-free survival (EFS) were analyzed by Cox analysis and disease-specific survival (DSS) by competing-risk regression. Results: With a median follow-up period of 57 months among survivors, 5- and 10-year OS rates were 68% and 56%, respectively; 5- and 10-year EFS rates were 62% and 56%, respectively; and 5- and 10-year cumulative incidences of HL-related deaths were 21% and 29%, respectively. On multivariate analysis, complete response to SC was independently associated with improved OS and EFS. Primary refractory disease and extranodal disease were independently associated with poor DSS. Eight patients had grade 3 or higher cardiac toxicity, with 3 deaths. Second malignancies developed in 10 patients, 5 of whom died. Conclusions: Accelerated IFRT followed by TLI and high-dose chemotherapy is an effective, feasible, and safe salvage strategy for patients with relapsed or refractory HL with excellent long-term OS, EFS, and DSS. Complete response to SC is the most important prognostic factor.« less

Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia

PubMed Central

Porter, David L.; Hwang, Wei-Ting; Frey, Noelle V.; Lacey, Simon F.; Shaw, Pamela A.; Loren, Alison W.; Bagg, Adam; Marcucci, Katherine T.; Shen, Angela; Gonzalez, Vanessa; Ambrose, David; Grupp, Stephan A.; Chew, Anne; Zheng, Zhaohui; Milone, Michael C.; Levine, Bruce L.; Melenhorst, Jan J.; June, Carl H.

2018-01-01

Patients with multiply relapsed or refractory chronic lymphocytic leukemia (CLL) have a poor prognosis. Chimeric antigen receptor (CAR)–modified T cells targeting CD19 have the potential to improve on the low complete response rates with conventional therapies by inducing sustained remissions in patients with refractory B cell malignancies. We previously reported preliminary results on three patients with refractory CLL. We report the mature results from our initial trial using CAR-modified T cells to treat 14 patients with relapsed and refractory CLL. Autologous T cells transduced with a CD19-directed CAR (CTL019) lentiviral vector were infused into patients with relapsed/refractory CLL at doses of 0.14 × 108 to 11 × 108 CTL019 cells (median, 1.6 × 108 cells). Patients were monitored for toxicity, response, expansion, and persistence of circulating CTL019 T cells. The overall response rate in these heavily pretreated CLL patients was 8 of 14 (57%), with 4 complete remissions (CR) and 4 partial remissions (PR). The in vivo expansion of the CAR T cells correlated with clinical responses, and the CAR T cells persisted and remained functional beyond 4 years in the first two patients achieving CR. No patient in CR has relapsed. All responding patients developed B cell aplasia and experienced cytokine release syndrome, coincident with T cell proliferation. Minimal residual disease was not detectable in patients who achieved CR, suggesting that disease eradication may be possible in some patients with advanced CLL. PMID:26333935

Intravenous ketamine for subacute treatment of refractory chronic migraine: a case series.

PubMed

Lauritsen, Clinton; Mazuera, Santiago; Lipton, Richard B; Ashina, Sait

2016-12-01

Refractory migraine is a challenging condition with great impact on health related quality of life. Intravenous (IV) ketamine has been previously used to treat various refractory pain conditions. We present a series of patients with refractory migraine treated with intravenous ketamine in the hospital setting. Based on retrospective chart review, we identified six patients with refractory migraine admitted from 2010 through 2014 for treatment with intravenous ketamine. Ketamine was administered using a standard protocol starting with a dose of 0.1 mg/kg/hr and increased by 0.1 mg/kg/hr every 3 to 4 h as tolerated until the target pain score of 3/10 was achieved and maintained for at least 8 h. Visual Analogue Scale (VAS) scores at time of hospital admission were obtained as well as average baseline VAS scores prior to ketamine infusion. A phone interview was conducted for follow-up of migraine response in the 3 to 6 months following ketamine infusion. The study sample had a median age of 36.5 years (range 29-54) and 83% were women. Pre-treatment pain scores ranged from 9 to 10. All patients achieved a target pain level of 3 or less for 8 h; the average ketamine infusion rate at target was 0.34 mg/kg/hour (range 0.12-0.42 mg/kg/hr). One patient reported a transient out-of-body hallucination following an increase in the infusion rate, which resolved after decreasing the rate. There were no other significant side effects. IV ketamine was safely administered in the hospital setting to patients with refractory chronic migraine. Treatment was associated with short term improvement in pain severity in 6 of 6 patients with refractory chronic migraine. Prospective placebo-controlled trials are needed to assess short term and long-term efficacy of IV ketamine in refractory chronic migraine.

Intratumoral heterogeneity and chemoresistance in nonseminomatous germ cell tumor of the testis.

PubMed

Bilen, Mehmet Asim; Hess, Kenneth R; Campbell, Matthew T; Wang, Jennifer; Broaddus, Russell R; Karam, Jose A; Ward, John F; Wood, Christopher G; Choi, Seungtaek L; Rao, Priya; Zhang, Miao; Naing, Aung; General, Rosale; Cauley, Diana H; Lin, Sue-Hwa; Logothetis, Christopher J; Pisters, Louis L; Tu, Shi-Ming

2016-12-27

Nonseminomatous germ cell tumor of the testis (NSGCT) is largely curable. However, a small group of patients develop refractory disease. We investigated the hypothesis that intratumoral heterogeneity contributes to the emergence of chemoresistance and the development of refractory tumor subtypes. Our institution's records for January 2000 through December 2010 included 275 patients whose primary tumor showed pure embryonal carcinoma (pure E); mixed embryonal carcinoma, yolk sac tumor, and teratoma (EYT); or mixed embryonal carcinoma, yolk sac tumor, seminoma, and teratoma (EYST). Patients with EYST had the highest cancer-specific mortality rate (P = .001). They tended to undergo somatic transformation (P = .0007). Two of 5 patients with clinical stage I EYST who had developed recurrence during active surveillance died of their disease. In this retrospective study, we evaluated consecutive patients who had been diagnosed with the three most common histological phenotypes of NSGCT. Chemoresistance was defined as the presence of teratoma, viable germ cell tumor, or somatic transformation in the residual tumor or the development of progressive or relapsed disease after chemotherapy. In a separate prospective study, we performed next-generation sequencing on tumor samples from 39 patients to identify any actionable genetic mutations. Our data suggest that patients with EYST in their primary tumor may harbor a potentially refractory NSGCT phenotype and are at increased risk of dying from disease. Despite intratumoral heterogeneity, improved patient selection and personalized care of distinct tumor subtypes may optimize the clinical outcome of patients with NSGCT.

Radiative engineering with refractory epsilon-near-zero metamaterials (Conference Presentation)

NASA Astrophysics Data System (ADS)

Dyachenko, Pavel N.; Molesky, Sean; Petrov, Alexander Y.; Störmer, Michael; Krekeler, Tobias; Lang, Slawa; Ritter, Martin; Jacob, Zubin; Eich, Manfred

2016-04-01

Improvement in high-temperature stable spectrally selective absorbers and emitters is integral for the further development of thermophotovoltaic (TPV), lighting and solar thermal applications. However, the high operational temperatures (T>1000oC) required for efficient energy conversion, along with application specific criteria such as the operational range of low bandgap semiconductors, greatly restrict what can be accomplished with natural materials. Motivated by this challenge, we demonstrate the first example of high temperature thermal radiation engineering with metamaterials. By employing the naturally selective thermal excitation of radiative modes that occurs near topological transitions, we show that thermally stable highly selective emissivity features are achieved for temperatures up to 1000°C with low angular dependence in a sub-micron thick refractory tungsten/hafnium dioxide epsilon-near-zero (ENZ) metamaterial. We also investigate the main mechanisms of thermal degradation of the fabricated refractory metamaterial both in terms of optical performance and structural stability using spectral analysis and energy-dispersive X-ray spectroscopy (EDS) techniques. Importantly, we observe chemical stability of the constituent materials for temperatures up to 1000°C and structural stability beyond 1100°C. The scalable fabrication, requiring magnetron sputtering, and thermally robust optical properties of this metamaterial approach are ideally suited to high temperature emitter applications such as lighting or TPV. Our findings provide a first concrete proof of radiative engineering with high temperature topological transition in ENZ metamaterials, and establish a clear path for implementation in TPV energy harvesting applications.

Advancements in the critical care management of status epilepticus.

PubMed

Bauerschmidt, Andrew; Martin, Andrew; Claassen, Jan

2017-04-01

Status epilepticus has a high morbidity and mortality. There are little definitive data to guide management; however, new recent data continue to improve understanding of management options of status epilepticus. This review examines recent advancements regarding the critical care management of status epilepticus. Recent studies support the initial treatment of status epilepticus with early and aggressive benzodiazepine dosing. There remains a lack of prospective randomized controlled trials comparing different treatment regimens. Recent data support further study of intravenous lacosamide as an urgent-control therapy, and ketamine and clobazam for refractory status epilepticus. Recent data support the use of continuous EEG to help guide treatment for all patients with refractory status epilepticus and to better understand epileptic activity that falls on the ictal-interictal continuum. Recent data also improve our understanding of the relationship between periodic epileptic activity and brain injury. Many treatments are available for status epilepticus and there are much new data guiding the use of specific agents. However, there continues to be a lack of prospective data supporting specific regimens, particularly in cases of refractory status epilepticus.

In-Situ Acoustic Measurements of Temperature Profile in Extreme Environments

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

Skliar, Mikhail

2015-03-31

A gasifier’s temperature is the primary characteristic that must be monitored to ensure its performance and the longevity of its refractory. One of the key technological challenges impacting the reliability and economics of coal and biomass gasification is the lack of temperature sensors that are capable of providing accurate, reliable, and long-life performance in an extreme gasification environment. This research has proposed, demonstrated, and validated a novel approach that uses a noninvasive ultrasound method that provides real-time temperature distribution monitoring across the refractory, especially the hot face temperature of the refractory. The essential idea of the ultrasound measurements of segmentalmore » temperature distribution is to use an ultrasound propagation waveguide across a refractory that has been engineered to contain multiple internal partial reflectors at known locations. When an ultrasound excitation pulse is introduced on the cold side of the refractory, it will be partially reflected from each scatterer in the US propagation path in the refractory wall and returned to the receiver as a train of partial echoes. The temperature in the corresponding segment can be determined based on recorded ultrasonic waveform and experimentally defined relationship between the speed of sound and temperature. The ultrasound measurement method offers a powerful solution to provide continuous real time temperature monitoring for the occasions that conventional thermal, optical and other sensors are infeasible, such as the impossibility of insertion of temperature sensor, harsh environment, unavailable optical path, and more. Our developed ultrasound system consists of an ultrasound engineered waveguide, ultrasound transducer/receiver, and data acquisition, logging, interpretation, and online display system, which is simple to install on the existing units with minimal modification on the gasifier or use with new units. This system has been successfully tested with a 100 kW pilot scale down flow oxyfuel combustor, capturing in real time temperature changes during all relevant combustion process changes. The ultrasound measurements have excellent agreement with thermo- couple measurements, and appear to be more sensitive to temperature changes before the thermocouples response, which is believed to be the first demonstration of ultrasound measurements segmental temperature distribution across refractories.« less

Refractory Access Disorders and the Organization of Concrete and Abstract Semantics: Do they Differ?

PubMed Central

Hamilton, A. Cris; Coslett, H. Branch

2010-01-01

Patients with “refractory semantic access deficits” demonstrate several unique features that make them important sources of insight into the organization of semantic representations. Here we attempt to replicate several novel findings from single-case studies reported in the literature. Patient UM– 103 displays the cardinal features of a “refractory semantic access deficit” and showed many of the same effects of semantic relatedness reported in the literature. However, when probing concrete and abstract words, this patient revealed very different patterns of performance compared to two previously reported patients. We discuss the implications of our data for models of semantic organization of abstract and concrete words. PMID:18569737

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

Erinjeri, Joseph P., E-mail: erinjerj@mskcc.org; Deodhar, Ajita; Thornton, Raymond H.

Hepatic encephalopathy is considered a contraindication to hepatic artery embolization. We describe a patient with a well-differentiated neuroendocrine tumor metastatic to the liver with refractory hepatic encephalopathy and normal liver function tests. The encephalopathy was refractory to standard medical therapy with lactulose. The patient's mental status returned to baseline after three hepatic artery embolization procedures. Arteriography and ultrasound imaging before and after embolization suggest that the encephalopathy was due to arterioportal shunting causing hepatofugal portal venous flow and portosystemic shunting. In patients with a primary or metastatic well-differentiated neuroendocrine tumor whose refractory hepatic encephalopathy is due to portosystemic shunting (rathermore » than global hepatic dysfunction secondary to tumor burden), hepatic artery embolization can be performed safely and effectively.« less

Enhancement of Oxidative Desulfurization Performance over UiO-66(Zr) by Titanium Ion Exchange.

PubMed

Ye, Gan; Qi, Hui; Li, Xiaolin; Leng, Kunyue; Sun, Yinyong; Xu, Wei

2017-07-19

Oxidative desulfurization is considered to be one of the most promising methods for producing ultra-low-sulfur fuels because it can effectively remove refractory sulfur-containing aromatic compounds under mild conditions. In this work, the oxidative desulfurization performance over UiO-66(Zr) is greatly enhanced by Ti ion exchange. This strategy is not only efficient for UiO-66(Zr) with crystal defects but also for UiO-66(Zr) with high crystallinity. In particular, the performance of UiO-66(Zr) with high crystallinity in the oxidative desulfurization of dibenzothiophene can be improved more than 11-fold, which can be mainly attributed to the introduction of active Ti sites. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Epstein-Barr virus-positive mucocutaneous ulcer in Crohn's disease. A condition to consider in immunosuppressed IBD patients.

PubMed

Juan, Alba; Lobatón, Triana; Tapia, Gustavo; Mañosa, Míriam; Cabré, Eduard; Domènech, Eugeni

2017-08-01

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a little known entity that can affect the oropharyngeal mucosa, the gastrointestinal tract and the skin. The main risk factor for the development of this lesion is immunosuppression. Because its features are similar to other Epstein-Barr virus-associated lymphoproliferative disorders, a differential diagnosis can sometimes prove challenging. Here, we report the case of a man diagnosed with Crohn's disease and treated with azathioprine and infliximab who developed ulceration at the rectum that was refractory to conventional medical treatment. Although the histological characteristics were suggestive of an EBVMCU, lymphoproliferative disease could not be ruled out. The patient did not improve after discontinuation of the treatment, a proctectomy was performed and the diagnosis of this disease was confirmed. Although very few cases of EBVMCU affecting the colon have been reported, its diagnosis should be always considered in refractory cases of inflammatory bowel disease with patients undergoing immunosuppressive treatment. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Intensive symptom control of opioid-refractory dyspnea in congestive heart failure: Role of milrinone in the palliative care unit.

PubMed

Silvestre, Julio; Montoya, Maria; Bruera, Eduardo; Elsayem, Ahmed

2015-12-01

We describe an exemplary case of congestive heart failure (CHF) symptoms controlled with milrinone. We also analyze the benefits and risks of milrinone administration in an unmonitored setting. We describe the case of a patient with refractory leukemia and end-stage CHF who developed severe dyspnea after discontinuation of milrinone. At that point, despite starting opioids, she had been severely dyspneic and anxious, requiring admission to the palliative care unit (PCU) for symptom control. After negotiation with hospital administrators, milrinone was administered in an unmonitored setting such as the PCU. A multidisciplinary team approach was also provided. Milrinone produced a dramatic improvement in the patient's symptom scores and performance status. The patient was eventually discharged to home hospice on a milrinone infusion with excellent symptom control. This case suggests that milrinone may be of benefit for short-term inpatient administration for dyspnea management, even in unmonitored settings and consequently during hospice in do-not-resuscitate (DNR) patients. This strategy may reduce costs and readmissions to the hospital related to end-stage CHF.

[Use of alternative donors for allogeneic haematopoietic cell transplantation in lymphoid neoplasms: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

PubMed

Gauthier, Jordan; Chantepie, Sylvain; Bouabdallah, Krimo; Jost, Edgar; Nguyen, Stéphanie; Gac, Anne-Claire; Damaj, Gandhi; Duléry, Rémy; Michallet, Mauricette; Delage, Jérémy; Lewalle, Philippe; Morschhauser, Franck; Salles, Gilles; Yakoub-Agha, Ibrahim; Cornillon, Jérôme

2017-12-01

Despite great improvements in the outcome of patients with lymphoma, some may still relapse or present with primary refractory disease. In these situations, allogeneic haematopoietic cell transplantation (allo-HCT) is a potentially curative option, in particular in the case of relapse after autologous stem cell transplantation. Recently, novel agents such as anti-PD1 and BTK inhibitors have started to challenge the use of allo-HCT for relapsed or refractory lymphoma. During the 2016 annual workshop of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), we performed a comprehensive review of the literature published in the last 10 years and established guidelines to clarify the indications and transplant modalities in this setting. This manuscript reports on general considerations regarding allo-HCT for lymphoma and elaborates on the use of alternative donors in this setting. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

[Allogeneic hematopoietic cell transplantation for Hodgkin's disease, mantle cell lymphoma and other rare entities: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

PubMed

Gauthier, Jordan; Chantepie, Sylvain; Bouabdallah, Krimo; Jost, Edgar; Nguyen, Stéphanie; Gac, Anne-Claire; Damaj, Gandhi; Duléry, Rémy; Michallet, Mauricette; Delage, Jérémy; Lewalle, Philippe; Morschhauser, Franck; Salles, Gilles; Yakoub-Agha, Ibrahim; Cornillon, Jérôme

2017-12-01

Despite great improvements in the outcome of patients with lymphoma, some may still relapse or present with primary refractory disease. In these situations, allogeneic haematopoietic cell transplantation is a potentially curative option, in particular in the case of relapse after autologous stem cell transplantation. Recently, novel agents such as anti-PD1 and BTK inhibitors have started to challenge the use of allogeneic haematopoietic cell transplantation for relapsed or refractory lymphoma. During the 2016 annual workshop of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), we performed a comprehensive review of the literature published in the last 10 years and established guidelines to clarify the indications and transplant modalities in this setting. This manuscript specifically reports on our conclusions regarding Hodgkin's lymphoma as well as rarer entities, such as T cell lymphomas. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

L-DOPS therapy for refractory orthostatic hypotension in autoimmune autonomic neuropathy.

PubMed

Gibbons, Christopher H; Vernino, Steven A; Kaufmann, Horacio; Freeman, Roy

2005-10-11

The authors report a 46-year-old woman with antibodies to the nicotinic acetylcholine receptor (NiAchR) of the autonomic ganglia. She presented with severe orthostatic intolerance refractory to treatment with midodrine, fludrocortisone, erythropoietin, vasopressin, salt, and fluid loading. Addition of L-threo-3,4-dihidroxyphenylserine (L-DOPS) substantially improved blood pressure and orthostatic tolerance. L-DOPS may benefit patients with severe orthostatic intolerance and be particularly effective in patients with ganglionic NiAchR antibodies.

REFRACTORY ARTICLE AND PROCESS OF MANUFACTURING SAME

DOEpatents

Hamilton, N.E.

1957-12-10

A method is described for fabricating improved uranium oxide crucibles. In the past, such crucibles have lacked mechanical strength due to the poor cohesion of the uranium oxide particles. This difficulty has now been overcome by admixing with the uranium oxide a quantity of a refractory oxide binder, and dry pressing and sintering the resulting mixture into the desired shape. Suitable as binders are BeO, CaO, Al/sub 2/C/sub 3/, and ThO/sub 2/ among others.

Nandrolone decanoate for the treatment of erythropoietin refractory anemia: a case series.

PubMed

Chawla, Bobby; Iqbal, Fahad M; Chawla, Manjeet S

2009-01-01

Erythropoietin refractory anemias represent a continuing and increasing burden on the healthcare system. The current practice of providing these patients with rHuEPO does not seem to be working. Fewer than 50% of patients respond in some studies. We demonstrate that androgens have multiple benefits in this population. They control anemia and stop transfusion dependence and improve nutritional parameters. In some patients, they also have a salutary effect on both white blood cell and platelet counts.

Palliative management of refractory dyspnea in COPD

PubMed Central

Uronis, Hope E; Currow, David C; Abernethy, Amy P

2006-01-01

COPD is a progressive illness with worldwide impact. Patients invariably reach a point at which they require palliative interventions. Dyspnea is the most distressing symptom experienced by these patients; when not relieved by traditional COPD management strategies it is termed “refractory dyspnea” and palliative approaches are required. The focus of care shifts from prolonging survival to reducing symptoms, increasing function, and improving quality of life. Numerous pharmacological and non-pharmacological interventions can achieve these goals, though evidence supporting their use is variable. This review provides a summary of the options for the management of refractory dyspnea in COPD, outlining currently available evidence and highlighting areas for further investigation. Topics include oxygen, opioids, psychotropic drugs, inhaled furosemide, Heliox, rehabilitation, nutrition, psychosocial support, breathing techniques, and breathlessness clinics. PMID:18046866

SNAP-8 refractory boiler development program

NASA Technical Reports Server (NTRS)

Fuller, R. A.

1974-01-01

Performance and endurance tests of the SNAP-8, SN-1 refractory metal boiler are described. The tests were successful and indicated that the boiler heat transfer area could be reduced significantly primarily because of the wetting characteristics of mercury on tantalum in a contaminant-free environment. A continuous endurance test of more than 10,000 hours was conducted without noticeable change in the thermal performance of the boiler. A conclusion of the metallographic examination of the boiler following the endurance test was that expected boiler life would be of the order of 40,000 hours at observed corrosion rates.

Light, Strong Insulating Tiles

NASA Technical Reports Server (NTRS)

Cordia, E.; Schirle, J.

1987-01-01

Improved lightweight insulating silica/aluminum borosilicate/silicon carbide tiles combine increased tensile strength with low thermal conductivity. Changes in composition substantially improve heat-insulating properties of silica-based refractory tile. Silicon carbide particles act as high-emissivity radiation scatterers in tile 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.

Ketogenic diet treatment for pediatric super-refractory status epilepticus.

PubMed

Appavu, Brian; Vanatta, Lisa; Condie, John; Kerrigan, John F; Jarrar, Randa

2016-10-01

We aimed to study whether ketogenic diet (KD) therapy leads to resolution of super-refractory status epilepticus in pediatric patients without significant harm. A retrospective review was performed at Phoenix Children's Hospital on patients with super-refractory status epilepticus undergoing ketogenic diet therapy from 2011 to 2015. Ten children with super-refractory status epilepticus, ages 2-16 years, were identified. 4/10 patients had immune mediated encephalitis, including Rasmussen encephalitis, anti-N-methyl-d-aspartate receptor encephalitis, and post-infectious mycoplasma encephalitis. Other etiologies included Lennox Gastaut Syndrome, non-ketotic hyperglycinemia, PCDH19 and GABRG2 genetic epilepsy, New Onset Refractory Status Epilepticus, and Febrile Infection-Related Epilepsy Syndrome. 4/10 patients' EEG features suggested focal with status epilepticus, and 6/10 suggested generalized with status epilepticus. Median hospital length was 61days and median ICU length was 27days. The median number of antiepileptic medications prior to diet initiation was 3.0 drugs, and the median after ketogenic diet treatment was 3.5 drugs. Median duration of status epilepticus prior to KD was 18days. 9/10 patients had resolution of super-refractory status epilepticus in a median of 7days after diet initiation. 8/9 patients were weaned off anesthesia within 15days of diet initiation, and within 1day of achieving ketonuria. 1/10 patients experienced side effects on the diet requiring supplementation. Most patients achieved resolution of status epilepticus on KD therapy, suggesting it could be an effective therapy that can be utilized early in the treatment of children with super refractory status epilepticus. Copyright © 2016. Published by Elsevier Ltd.

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

[Real-life efficacy and tolerability of methocarbamol in patients suffering from refractory muscle-related low/back pain - Results of a health care research project based on data from the German pain practice registry].

PubMed

Überall, Michael A; Emrich, Oliver M D; Müller-Schwefe, Gerhard H H

2017-12-01

Subacute, muscle-related low/back pain (L/BP) is known to be difficult to treat and frequently requires more specific causal-oriented treatments with agents improving the increased muscle tone. Currently, only methocarbamol is approved and available for the 1st-line treatment of patients with muscle-related L/BP in Germany - however, without sufficient data on longer lasting effects (> 1 week) in elsewhere refractory patients. Noninterventional cohort study, based on anonymized routine data of the German pain practice registry; retrospective evaluation of patients with refractory L/BP, who first time received a treatment with methocarbamol between October 1st until December 31st, 2015, and who documented their response to treatment with the standardized and validated instruments of the German pain questionnaire over at least 4 weeks (n = 251 patients). During the 4-week evaluation period, patients reported a highly significant and clinically relevant improvement of pain intensity (from 53.0 ± 10.5 to 19.0 ± 10.0 mm VAS), pain-related disability in daily life (mPDI: from 42.1 ± 12.5 to 15.5 ± 10.8) and quality of life (QLIP: from 18.6 ± 6.3 to 34.0 ± 5.5; all changes p < 0.001 vs. baseline). Corresponding 50% response rates were 81.7 (n = 205), 68.5 (n = 172) und 91.6 (n = 230) %. In parallel, lumbar mobility (measured with the Schober's test) improved from 10.7 ± 0.7 to 14.7 ± 0.7 cm (p < 0,001). Overall, seven patients recorded eight minor treatment-related adverse events, which all resolved spontaneously during treatment without any specific countermeasures. Under the conditions of daily life, patients with elsewhere refractory L/BP reported a significant and clinically relevant improvement of pain intensity, pain-related disability and quality of life in response to a 4-week treatment with methocarbamol.

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.

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.

[Changes of heart electrophysiological parameters after destruction of epicardial subplexuses that innervate sinoatrial node].

PubMed

Kulboka, Arūnas; Veikutis, Vincentas; Pauza, Dainius Haroldas; Lekas, Raimundas

2003-01-01

The aims of present study were to verify the topography of the intracardiac nerve subplexuses (INS) by using electrophysiological methods, its relations with sinoatrial (SA) node function and to investigate possibility of selective surgical SA node denervation. Fifteen mongrel dogs of either sex weighing 8 to 15 kg were used for electrophysiological studies. Both cervical vagosympathetic trunks were isolated and crushed by tight ligatures. Nervus subplexuses destructions were performed by cryocoagulation in three zones located around the right superior vena cava: ventral, lateral and dorsal. The sinus rhythm, SA node function recovery time, AV node conductivity, AV node and atrial effective refractory period were measured. Five experiments in each of three zones were performed. Experimental data show that destruction of the epicardial nerves has different effect on electrophysiological parameters. After destruction of the anterior zone of the right atrium the sinus rhythm decreased on an average by 11.6%; SA node function recovery time prolonged by 7.2%; AV node conductivity decreased by 13.1%; AV node effective refractory period prolonged by 12.9% and atrial effective refractory period, by 10.9 %. Measurements of electrophysiological parameters after intravenous injection of atropine sulphate show that sinus rhythm decreased on an average by 23.4%; SA node function recovery time increased by 9.1%; the conductivity of AV node decreased by 10.2%; AV node effective refractory period prolonged by 15.4% and atrial effective refractory period, by 13.2%. After destruction of the intracardiac nerves of the lateral zone, the sinus rhythm decreased by 15.7%; SA node function recovery time increased by 16.3%; AV node conductivity decreased by 8.3%; AV node effective refractory period and atrial effective refractory period prolonged by 11.9% and 10.0%, respectively. After the atropine sulphate intravenous injection, the sinus rhythm decreased on an average by 7.1%, SA node function recovery time prolonged by 7.1%, AV conductivity decreased by 9.1%, AV node effective refractory period increased by 12.4%, and atrial effective refractory period prolonged by 12.5%. After destruction of the nerves in the dorsal zone the changes of electrophysiological parameters were opposite to those obtained after destruction of the nerve tracts in the anterior or lateral zones: the sinus rhythm increased on an average by 4.3%; SA node function recovery time shortened by 8.8%; AV conductivity increased by 9.7%; AV node and atrial effective refractory period decreased by 12.3% and 12.1%, respectively. After intravenous atropine sulphate infusion, sinus rhythm decreased on an average by 8.3%; SA node function recovery time prolonged by 9.6%; AV node conductivity decreased by 5%; AV node and atrial effective refractory period prolonged by 4.2% and 5.2%, respectively. The average changes of electrophysiological parameters before and after INS destruction shows that cryocoagulation of ventral and lateral zones eliminates the effects of sympathetic tone to SA and AV nodal activity. Cryocoagulation of dorsal zone eliminates the effects of nervus vagus to both nodal structures. These findings shows the possibility alter or correct SA node function by making selective surgical SA node denervation.

Development and Processing of Nickel Aluminide-Carbide Alloys

NASA Technical Reports Server (NTRS)

Newport, Timothy Scott

1996-01-01

With the upper temperature limit of the Ni-based superalloys attained, a new class of materials is required. Intermetallics appear as likely candidates because of their attractive physical properties. With a relatively low density, high thermal conductivity, excellent oxidation resistance, high melting point, and simple crystal structure, nickel aluminide (NiAl) appears to be a potential candidate. However, NiAl is limited in structural applications due to its low room temperature fracture toughness and poor elevated temperature strength. One approach to improving these properties has been through the application of eutectic composites. Researchers have shown that containerless directional solidification of NiAl-based eutectic alloys can provide improvement in both the creep strength and fracture toughness. Although these systems have shown improvements in the mechanical properties, the presence of refractory metals increases the density significantly in some alloys. Lower density systems, such as the carbides, nitrides, and borides, may provide NiAl-based eutectic structure. With little or no information available on these systems, experimental investigation is required. The objective of this research was to locate and develop NiAl-carbide eutectic alloys. Exploratory arc-melts were performed in NiAl-refractory metal-C systems. Refractory metal systems investigated included Co, Cr, Fe, Hf, Mo, Nb, Ta, Ti, W, and Zr. Systems containing carbides with excellent stability (i.e.,HfC, NbC, TaC, TiC, and ZrC) produced large blocky cubic carbides in an NiAl matrix. The carbides appeared to have formed in the liquid state and were randomly distributed throughout the polycrystalline NiAl. The Co, Cr, Fe, Mo, and W systems contained NiAl dendrites with a two-phase interdendritic microconstituent present. Of these systems, the NiAl-Mo-C system had the most promising microstructure for in-situ composites. Three processing techniques were used to evaluate the NiAl-Mo-C system: arc-melting, slow cooling, and containerless directional solidification. Arc-melting provided a wide range of compositions in an economical and simple fashion. The slow cooled ingots provided larger ingots and slower cooling rates than arc-melting. Directional solidification was used to produce in-situ composites consisting of NiAl reinforced with molybdenum carbides.

IMPROVED CORROSION RESISTANCE OF ALUMINA REFRACTORIES

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

John P. Hurley; Patty L. Kleven

2001-09-30

The initial objective of this project was to do a literature search to define the problems of refractory selection in the metals and glass industries. The problems fall into three categories: Economic--What do the major problems cost the industries financially? Operational--How do the major problems affect production efficiency and impact the environment? and Scientific--What are the chemical and physical mechanisms that cause the problems to occur? This report presents a summary of these problems. It was used to determine the areas in which the EERC can provide the most assistance through bench-scale and laboratory testing. The final objective of thismore » project was to design and build a bench-scale high-temperature controlled atmosphere dynamic corrosion application furnace (CADCAF). The furnace will be used to evaluate refractory test samples in the presence of flowing corrodents for extended periods, to temperatures of 1600 C under controlled atmospheres. Corrodents will include molten slag, steel, and glass. This test should prove useful for the glass and steel industries when faced with the decision of choosing the best refractory for flowing corrodent conditions.« less

The anti-malarial chloroquine overcomes Primary resistance and restores sensitivity to Trastuzumab in HER2-positive breast cancer

PubMed Central

Cufí, Sílvia; Vazquez-Martin, Alejandro; Oliveras-Ferraros, Cristina; Corominas-Faja, Bruna; Cuyàs, Elisabet; López-Bonet, Eugeni; Martin-Castillo, Begoña; Joven, Jorge; Menendez, Javier A.

2013-01-01

Autophagy may control the de novo refractoriness of HER2 gene-amplified breast carcinomas to the monoclonal antibody trastuzumab (Herceptin). Tumor cells originally obtained from a patient who rapidly progressed on trastuzumab ab initio display increased cellular levels of the LC3-II protein—a finding that correlates with increased numbers of autophagosomes—and decreased levels of the autophagy receptor p62/SQSTM1, a protein selectively degraded by autophagy. Trastuzumab-refractory cells are in a state of “autophagy addiction” because genetic ablation of autophagy-specific genes (ATG8, ATG5, ATG12) notably reduces intrinsic refractoriness to trastuzumab. When the anti-malarial lysosomotropic drug chloroquine impedes autophagic resolution of the accumulation of autophagolysosomes formed in the presence of trastuzumab, cells commit to die by apoptosis. Accordingly, combination treatment with trastuzumab and chloroquine radically suppresses tumor growth by > 90% in a tumor xenograft completely refractory to trastuzumab. Adding chloroquine to trastuzumab-based regimens may therefore improve outcomes among women with autophagy-addicted HER2-positive breast cancer. PMID:23965851

Development of a New Ferrous Aluminosilicate Refractory Material for Investment Casting of Aluminum Alloys

NASA Astrophysics Data System (ADS)

Yuan, Chen; Jones, Sam; Blackburn, Stuart

2012-12-01

Investment casting is a time-consuming, labour intensive process, which produces complex, high value-added components for a variety of specialised industries. Current environmental and economic pressures have resulted in a need for the industry to improve current casting quality, reduce manufacturing costs and explore new markets for the process. Alumino-silicate based refractories are commonly used as both filler and stucco materials for ceramic shell production. A new ceramic material, norite, is now being produced based on ferrous aluminosilicate chemistry, having many potential advantages when used for the production of shell molds for casting aluminum alloy. This paper details the results of a direct comparison made between the properties of a ceramic shell system produced with norite refractories and a typical standard refractory shell system commonly used in casting industry. A range of mechanical and physical properties of the systems was measured, and a full-scale industrial casting trial was also carried out. The unique properties of the norite shell system make it a promising alternative for casting aluminum based alloys in the investment foundry.

Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers

PubMed Central

Tang, Fei; Hartz, Anika M. S.; Bauer, Björn

2017-01-01

Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs), about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against several major theories, including the pharmacokinetic hypothesis, neural network hypothesis, intrinsic severity hypothesis, gene variant hypothesis, target hypothesis, and transporter hypothesis. The discussion is mainly focused on the transporter hypothesis, where clinical and experimental data are discussed on multidrug transporter overexpression, substrate profiles of ASDs, mechanism of transporter upregulation, polymorphisms of transporters, and the use of transporter inhibitors. Finally, future perspectives are presented for the improvement of current hypotheses and the development of treatment strategies as guided by the current understanding of refractory epilepsy. PMID:28729850

The anti-malarial chloroquine overcomes primary resistance and restores sensitivity to trastuzumab in HER2-positive breast cancer.

PubMed

Cufí, Sílvia; Vazquez-Martin, Alejandro; Oliveras-Ferraros, Cristina; Corominas-Faja, Bruna; Cuyàs, Elisabet; López-Bonet, Eugeni; Martin-Castillo, Begoña; Joven, Jorge; Menendez, Javier A

2013-01-01

Autophagy may control the de novo refractoriness of HER2 gene-amplified breast carcinomas to the monoclonal antibody trastuzumab (Herceptin). Tumor cells originally obtained from a patient who rapidly progressed on trastuzumab ab initio display increased cellular levels of the LC3-II protein--a finding that correlates with increased numbers of autophagosomes--and decreased levels of the autophagy receptor p62/SQSTM1, a protein selectively degraded by autophagy. Trastuzumab-refractory cells are in a state of "autophagy addiction" because genetic ablation of autophagy-specific genes (ATG8, ATG5, ATG12) notably reduces intrinsic refractoriness to trastuzumab. When the anti-malarial lysosomotropic drug chloroquine impedes autophagic resolution of the accumulation of autophagolysosomes formed in the presence of trastuzumab, cells commit to die by apoptosis. Accordingly, combination treatment with trastuzumab and chloroquine radically suppresses tumor growth by > 90% in a tumor xenograft completely refractory to trastuzumab. Adding chloroquine to trastuzumab-based regimens may therefore improve outcomes among women with autophagy-addicted HER2-positive breast cancer.

Outcomes in Children Treated with Pentobarbital Infusion for Refractory and Super-Refractory Status Epilepticus.

PubMed

Erklauer, Jennifer; Graf, Jeanine; McPherson, Mona; Anderson, Anne; Wilfong, Angus; Minard, Charles G; Loftis, Laura

2018-03-26

Functional neurologic outcome for children with refractory and super-refractory status epilepticus has not been well defined. Retrospective chart review including children age 0-17 years who received pentobarbital infusion from 2003 to 2016 for status epilepticus. Outcomes were defined in terms of mortality, need for new medical technology assistance at hospital discharge and functional neurologic outcome determined by pediatric cerebral performance category score (PCPC). Potential patient characteristics associated with functional neurologic outcome including age, sex, ethnicity, etiology of the status epilepticus, and duration of pentobarbital infusion were evaluated. Forty children met inclusion criteria. In-hospital mortality was 30% (12/40). Of survivors, 21% (6/28) returned to baseline PCPC while half (14/28) declined in function ≥ 2 PCPC categories at hospital discharge. 25% (7/28) of survivors required tracheostomy and 27% (7/26) required new gastrostomy. Seizures persisted at discharge for most patients with new onset status epilepticus while the majority of patients with known epilepsy returned to baseline seizure frequency. Etiology (p = 0.015), PCPC at admission (p = 0.0006), new tracheostomy (p = 0.012), and new gastrostomy tube (p = 0.012) were associated with increase in PCPC score ≥ 2 categories in univariable analysis. Duration of pentobarbital infusion (p = 0.005) and length of hospital stay (p = 0.056) were longer in patients who demonstrated significant decline in neurologic function. None of these variables maintained statistical significance when multiple logistic regression model adjusting for PCPC score at admission was applied. At long-term follow-up, 36% (8/22) of children demonstrated improvement in PCPC compared to discharge and 23% (5/22) showed deterioration including three additional deaths. Mortality in this population was high. The majority of children experienced some degree of disability at discharge. Despite prolonged pentobarbital infusion, there were cases of survival with good neurologic outcome.

Reforming of fuel inside fuel cell generator

DOEpatents

Grimble, Ralph E.

1988-01-01

Disclosed is an improved method of reforming a gaseous reformable fuel within a solid oxide fuel cell generator, wherein the solid oxide fuel cell generator has a plurality of individual fuel cells in a refractory container, the fuel cells generating a partially spent fuel stream and a partially spent oxidant stream. The partially spent fuel stream is divided into two streams, spent fuel stream I and spent fuel stream II. Spent fuel stream I is burned with the partially spent oxidant stream inside the refractory container to produce an exhaust stream. The exhaust stream is divided into two streams, exhaust stream I and exhaust stream II, and exhaust stream I is vented. Exhaust stream II is mixed with spent fuel stream II to form a recycle stream. The recycle stream is mixed with the gaseous reformable fuel within the refractory container to form a fuel stream which is supplied to the fuel cells. Also disclosed is an improved apparatus which permits the reforming of a reformable gaseous fuel within such a solid oxide fuel cell generator. The apparatus comprises a mixing chamber within the refractory container, means for diverting a portion of the partially spent fuel stream to the mixing chamber, means for diverting a portion of exhaust gas to the mixing chamber where it is mixed with the portion of the partially spent fuel stream to form a recycle stream, means for injecting the reformable gaseous fuel into the recycle stream, and means for circulating the recycle stream back to the fuel cells.

Reforming of fuel inside fuel cell generator

DOEpatents

Grimble, R.E.

1988-03-08

Disclosed is an improved method of reforming a gaseous reformable fuel within a solid oxide fuel cell generator, wherein the solid oxide fuel cell generator has a plurality of individual fuel cells in a refractory container, the fuel cells generating a partially spent fuel stream and a partially spent oxidant stream. The partially spent fuel stream is divided into two streams, spent fuel stream 1 and spent fuel stream 2. Spent fuel stream 1 is burned with the partially spent oxidant stream inside the refractory container to produce an exhaust stream. The exhaust stream is divided into two streams, exhaust stream 1 and exhaust stream 2, and exhaust stream 1 is vented. Exhaust stream 2 is mixed with spent fuel stream 2 to form a recycle stream. The recycle stream is mixed with the gaseous reformable fuel within the refractory container to form a fuel stream which is supplied to the fuel cells. Also disclosed is an improved apparatus which permits the reforming of a reformable gaseous fuel within such a solid oxide fuel cell generator. The apparatus comprises a mixing chamber within the refractory container, means for diverting a portion of the partially spent fuel stream to the mixing chamber, means for diverting a portion of exhaust gas to the mixing chamber where it is mixed with the portion of the partially spent fuel stream to form a recycle stream, means for injecting the reformable gaseous fuel into the recycle stream, and means for circulating the recycle stream back to the fuel cells. 1 fig.

Autologous transplantation of the internal limiting membrane for refractory macular holes.

PubMed

Morizane, Yuki; Shiraga, Fumio; Kimura, Shuhei; Hosokawa, Mio; Shiode, Yusuke; Kawata, Tetsuhiro; Hosogi, Mika; Shirakata, Yukari; Okanouchi, Toshio

2014-04-01

To determine the effectiveness of autologous transplantation of the internal limiting membrane (ILM) for refractory macular holes. Prospective, interventional case series. Ten eyes of 10 consecutive patients who underwent autologous transplantation of the ILM for the treatment of refractory macular holes were studied. The primary diseases in these patients were large idiopathic macular holes that had existed for more than 1 year (4 eyes), a traumatic macular hole (1 eye), myopic foveoschisis (2 eyes), foveoschisis resulting from pit-macular syndrome (2 eyes), and proliferative diabetic retinopathy (1 eye). Apart from the 5 eyes with idiopathic or traumatic macular holes, macular holes developed in the other 5 eyes after initial vitrectomies with ILM removal. In all eyes, regular macular hole surgery failed to achieve closure. The main outcome measures used in this study were macular hole closure and best-corrected visual acuity (BCVA). Macular holes were closed successfully in 9 eyes (90%) after autologous transplantation of the ILM. The postoperative BCVAs were significantly better than the preoperative BCVAs (P = .007, paired t test). Postoperative BCVAs improved by more than 0.2 logarithm of the minimal angle of resolution units in 8 eyes (80%) and were unchanged in 2 eyes (20%). Although this is a pilot study, the results suggest that autologous transplantation of the ILM may contribute to improved anatomic and visual outcomes in the treatment of refractory macular holes and may warrant further investigation. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of a combination of flip and zooming stimuli on the performance of a visual brain-computer interface for spelling.

PubMed

Cheng, Jiao; Jin, Jing; Daly, Ian; Zhang, Yu; Wang, Bei; Wang, Xingyu; Cichocki, Andrzej

2018-02-13

Brain-computer interface (BCI) systems can allow their users to communicate with the external world by recognizing intention directly from their brain activity without the assistance of the peripheral motor nervous system. The P300-speller is one of the most widely used visual BCI applications. In previous studies, a flip stimulus (rotating the background area of the character) that was based on apparent motion, suffered from less refractory effects. However, its performance was not improved significantly. In addition, a presentation paradigm that used a "zooming" action (changing the size of the symbol) has been shown to evoke relatively higher P300 amplitudes and obtain a better BCI performance. To extend this method of stimuli presentation within a BCI and, consequently, to improve BCI performance, we present a new paradigm combining both the flip stimulus with a zooming action. This new presentation modality allowed BCI users to focus their attention more easily. We investigated whether such an action could combine the advantages of both types of stimuli presentation to bring a significant improvement in performance compared to the conventional flip stimulus. The experimental results showed that the proposed paradigm could obtain significantly higher classification accuracies and bit rates than the conventional flip paradigm (p<0.01).

Development of Antibodies Against Novel Cell Surface Proteins In Hormone Refractory Prostate Cancer. Addendum

DTIC Science & Technology

2011-07-01

marker of hormone refractory metastatic prostate cancer. Clin Cancer Res, 2005. 15: 2237- 43 . 3. Tomita K, van Bokhoven A, van Leenders GJ, Ruijter...Santa Cruz Biotechnology), vimentin, Ki-67 (DakoCytomation) and caspase-3 (Cell Signaling Technology). Flow cytometry was performed with N...transduced cells were labeled with N-cadherin–specific antibody and sorted by flow cytometry , gating for a GFP-positive, N-cadherinlow population. The

Refractory seizures due to a dural-based cavernoma masquerading as a meningioma.

PubMed

Zeng, Xianwei; Mahta, Ali; Kim, Ryan Y; Saad, Ali G; Kesari, Santosh

2012-04-01

A 37-year-old female presented with medically intractable complex partial seizures with secondary generalization. She was found to have a dural-based lesion with radiologic features of meningioma. A gross total resection was performed and pathology confirmed a diagnosis of cavernous angioma and she became seizure free after the surgical resection. Cavernous angioma should be considered in differential diagnosis of a dural-based lesion manifesting with refractory seizures.

Materials review for improved automotive gas turbine engine. [superalloys, refractory alloys, and ceramics

NASA Technical Reports Server (NTRS)

Belleau, C.; Ehlers, W. L.; Hagen, F. A.

1978-01-01

The potential role of superalloys, refractory alloys, and ceramics in the hottest sections of engines operating with turbine inlet temperatures as high as 1370 C is examined. The convential superalloys, directionally solidified eutectics, oxide dispersion strenghened alloys, and tungsten fiber reinforced superalloys are reviewed and compared on the basis of maximum turbine blade temperature capability. Improved high temperature protective coatings and special fabrication techniques for these advanced alloys are discussed. Chromium, columbium, molybdenum, tantalum, and tungsten alloys are also reviewed. Molbdenum alloys are found to be the most suitable for mass produced turbine wheels. Various forms and fabrication processes for silicon nitride, silicon carbide, and SIALON's are investigated for use in highstress and medium stress high temperature environments.

Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest: The State of the Evidence and Framework for Application.

PubMed

Grunau, Brian; Hornby, Laura; Singal, Rohit K; Christenson, Jim; Ortega-Deballon, Ivan; Shemie, Sam D; Bashir, Jamil; Brooks, Steve C; Callaway, Clifton W; Guadagno, Elena; Nagpal, Dave

2018-02-01

Out-of-hospital cardiac arrest (OHCA) affects 134 per 100,000 citizens annually. Extracorporeal cardiopulmonary resuscitation (ECPR), providing mechanical circulatory support, may improve the likelihood of survival among those with refractory OHCA. Compared with in-hospital ECPR candidates, those in the out-of-hospital setting tend to be sudden unexpected arrests in younger and healthier patients. The aims of this review were to summarize, and identify the limitations of, the evidence evaluating ECPR for OHCA, and to provide an approach for ECPR program application. Although there are many descriptions of ECPR-treated cohorts, we identified a paucity of robust data showing ECPR effectiveness compared with conventional resuscitation. However, it is highly likely that ECPR, provided after a prolonged attempt with conventional resuscitation, does benefit select patient populations compared with conventional resuscitation alone. Although reliable data showing the optimal patient selection criteria for ECPR are lacking, most implementations sought young previously healthy patients with rapid high-quality cardiopulmonary resuscitation. Carefully planned development of ECPR programs, in high-performing emergency medical systems at experienced extracorporeal membrane oxygenation centres, may be reasonable as part of systematic efforts to determine ECPR effectiveness and globally improve care. Protocol evaluation requires regional-level assessment, examining the incremental benefit of survival compared with standard care, while accounting for resource utilization. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study.

PubMed

Dreyling, Martin; Jurczak, Wojciech; Jerkeman, Mats; Silva, Rodrigo Santucci; Rusconi, Chiara; Trneny, Marek; Offner, Fritz; Caballero, Dolores; Joao, Cristina; Witzens-Harig, Mathias; Hess, Georg; Bence-Bruckler, Isabelle; Cho, Seok-Goo; Bothos, John; Goldberg, Jenna D; Enny, Christopher; Traina, Shana; Balasubramanian, Sriram; Bandyopadhyay, Nibedita; Sun, Steven; Vermeulen, Jessica; Rizo, Aleksandra; Rule, Simon

2016-02-20

Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma. This randomised, open-label, multicentre, phase 3 clinical trial enrolled patients with relapsed or refractory mantle-cell lymphoma confirmed by central pathology in 21 countries who had received one or more rituximab-containing treatments. Patients were stratified by previous therapy and simplified mantle-cell lymphoma international prognostic index score, and were randomly assigned with a computer-generated randomisation schedule to receive daily oral ibrutinib 560 mg or intravenous temsirolimus (175 mg on days 1, 8, and 15 of cycle 1; 75 mg on days 1, 8, and 15 of subsequent 21-day cycles). Randomisation was balanced by using randomly permuted blocks. The primary efficacy endpoint was progression-free survival assessed by a masked independent review committee with the primary hypothesis that ibrutinib compared with temsirolimus significantly improves progression-free survival. The analysis followed the intention-to-treat principle. The trial is ongoing and is registered with ClinicalTrials.gov (number NCT01646021) and with the EU Clinical Trials Register, EudraCT (number 2012-000601-74). Between Dec 10, 2012, and Nov 26, 2013, 280 patients were randomised to ibrutinib (n=139) or temsirolimus (n=141). Primary efficacy analysis showed significant improvement in progression-free survival (p<0·0001) for patients treated with ibrutinib versus temsirolimus (hazard ratio 0·43 [95% CI 0·32-0·58]; median progression-free survival 14·6 months [95% CI 10·4-not estimable] vs 6·2 months [4·2-7·9], respectively). Ibrutinib was better tolerated than temsirolimus, with grade 3 or higher treatment-emergent adverse events reported for 94 (68%) versus 121 (87%) patients, and fewer discontinuations of study medication due to adverse events for ibrutinib versus temsirolimus (9 [6%] vs 36 [26%]). Ibrutinib treatment resulted in significant improvement in progression-free survival and better tolerability versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma. These data lend further support to the positive benefit-risk ratio for ibrutinib in relapsed or refractory mantle-cell lymphoma. Janssen Research & Development, LLC. Copyright © 2016 Elsevier Ltd. All rights reserved.

Granisetron transdermal system improves refractory nausea and vomiting in gastroparesis.

PubMed

Simmons, Kellie; Parkman, Henry P

2014-06-01

Symptoms of gastroparesis include nausea and vomiting, which can markedly diminish quality of life. Nausea and vomiting can also make treatment with oral antiemetics problematic. Our aim was to determine whether treatment-resistant nausea and vomiting in patients with gastroparesis improve after granisetron transdermal patch (GTP) therapy. In an open-label pilot study, patients with gastroparesis and symptoms of nausea and vomiting refractory to conventional treatment were treated with GTP. After 2 weeks, patients were asked to assess their therapeutic response using the Clinical Patient Grading Assessment Scale (CPGAS; +7 = completely better; 0 = no change; -7 = very considerably worse). Responders were defined as CPGAS score >0, non-responders as ≤0. Patients (n = 36) were treated with GTP. Of these 36 patients, one patient discontinued treatment due to the GTP not adhering to the skin. Of the remaining 35 patients, 18 improved, 15 remained the same, and two worsened. The average CPGAS score was +1.8 ± 0.4 (SEM) (P < 0.05 vs 0). Of the 18 patients with improvement, the average CPGAS score was +3.7 ± 0.3 (SEM), corresponding to "somewhat" to "moderately better" improvement in nausea/vomiting. Side effects occurred in nine patients: four developed constipation, three patients had skin rash, and two reported headaches. GTP was moderately effective in reducing refractory symptoms of nausea and/or vomiting from gastroparesis in 50% of patients. Mild side effects were reported by 25% of patients. GTP may be an effective treatment for nausea and vomiting in gastroparesis, and further study is warranted.

Low dose Naltrexone for induction of remission in inflammatory bowel disease patients.

PubMed

Lie, Mitchell R K L; van der Giessen, Janine; Fuhler, Gwenny M; de Lima, Alison; Peppelenbosch, Maikel P; van der Ent, Cokkie; van der Woude, C Janneke

2018-03-09

Around 30% of patients with inflammatory bowel disease (IBD) are refractory to current IBD drugs or relapse over time. Novel treatments are called for, and low dose Naltrexone (LDN) may provide a safe, easily accessible alternative treatment option for these patients. We investigated the potential of LDN to induce clinical response in therapy refractory IBD patients, and investigated its direct effects on epithelial barrier function. Patients not in remission and not responding to conventional therapy were offered to initiate LDN as a concomitant treatment. In total 47 IBD patients prescribed LDN were followed prospectively for 12 weeks. Where available, endoscopic remission data, serum and biopsies were collected. Further the effect of Naltrexone on wound healing (scratch assay), cytokine production and endoplasmic reticulum (ER) stress (GRP78 and CHOP western blot analysis, immunohistochemistry) were investigated in HCT116 and CACO2 intestinal epithelial cells, human IBD intestinal organoids and patient samples. Low dose Naltrexone induced clinical improvement in 74.5%, and remission in 25.5% of patients. Naltrexone improved wound healing and reduced ER stress induced by Tunicamycin, lipopolysaccharide or bacteria in epithelial barriers. Inflamed mucosa from IBD patients showed high ER stress levels, which was reduced in patients treated with LDN. Cytokine levels in neither epithelial cells nor serum from IBD patients were affected. Naltrexone directly improves epithelial barrier function by improving wound healing and reducing mucosal ER stress levels. Low dose Naltrexone treatment is effective and safe, and could be considered for the treatment of therapy refractory IBD patients.

Adjunctive memantine in clozapine-treated refractory schizophrenia: an open-label 1-year extension study.

PubMed

Veerman, S R T; Schulte, P F J; Deijen, J B; de Haan, L

2017-01-01

In a recent placebo-controlled, double-blind crossover trial (n = 52), significant beneficial effects on memory (d = 0.30) and negative symptoms (d = 0.29) were found after 12 weeks of memantine augmentation in patients with clozapine-refractory schizophrenia. In this open-label 1-year extension study we report the long-term effects and tolerability of memantine add-on therapy to clozapine. Completers of the first trial who experienced beneficial effects during 12 weeks of memantine treatment received memantine for 1 year. Primary endpoints were memory and executive function using the Cambridge Neuropsychological Test Automated Battery, the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression Severity Scale (CGI-S). Of 31 randomized controlled trial completers who experienced beneficial effects from memantine, 24 received memantine for 1 year. The small improvement in memory found in the memantine condition in the placebo-controlled trial remained stable in the extension study. Executive function did not improve. After 26 weeks of memantine add-on therapy to clozapine, PANSS negative symptoms (r = 0.53), PANSS positive symptoms (r = 0.50) and PANSS total symptoms (r = 0.54) significantly improved. Even further significant improvement in all these measures was observed between 26 weeks and 52 weeks of memantine, with effect sizes varying from 0.39 to 0.51. CGI-S showed a non-significant moderate improvement at 26 weeks (r = 0.36) and 52 weeks (r = 0.34). Memantine was well tolerated without serious adverse effects. In the 1-year extension phase the favourable effect of adjunctive memantine on memory was sustained and we observed further improvement of negative, positive and overall symptoms in patients with clozapine-treated refractory schizophrenia.

Commercial low-Btu coal-gasification plant. Feasibility study: General Refractories Company, Florence, Kentucky. Volume I. Project summary. [Wellman-Galusha

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

None

1981-11-01

In response to a 1980 Department of Energy solicitation, the General Refractories Company submitted a Proposal for a feasibility study of a low Btu gasification facility for its Florence, KY plant. The proposed facility would substitute low Btu gas from a fixed bed gasifier for natural gas now used in the manufacture of insulation board. The Proposal from General Refractories was prompted by a concern over the rising costs of natural gas, and the anticipation of a severe increase in fuel costs resulting from deregulation. The proposed feasibility study is defined. The intent is to provide General Refractories with themore » basis upon which to determine the feasibility of incorporating such a facility in Florence. To perform the work, a Grant for which was awarded by the DOE, General Refractories selected Dravo Engineers and Contractors based upon their qualifications in the field of coal conversion, and the fact that Dravo has acquired the rights to the Wellman-Galusha technology. The LBG prices for the five-gasifier case are encouraging. Given the various natural gas forecasts available, there seems to be a reasonable possibility that the five-gasifier LBG prices will break even with natural gas prices somewhere between 1984 and 1989. General Refractories recognizes that there are many uncertainties in developing these natural gas forecasts, and if the present natural gas decontrol plan is not fully implemented some financial risks occur in undertaking the proposed gasification facility. Because of this, General Refractories has decided to wait for more substantiating evidence that natural gas prices will rise as is now being predicted.« less

Sodium oxybate for idiopathic REM sleep behavior disorder: a report on two patients.

PubMed

Moghadam, Keivan Kaveh; Pizza, Fabio; Primavera, Alberto; Ferri, Raffaele; Plazzi, Giuseppe

2017-04-01

REM-sleep behavior disorder (RBD) therapy is based on small to medium-sized case series, as no large controlled clinical trials have been performed. The most used and widely recognized effective drugs are clonazepam and melatonin, with anecdotal reports on the potential benefit of other drug classes. We report on two patients suffering from idiopathic RBD presenting with almost nightly complex and violent episodes, refractory to conventional drugs. Both patients, after informed consent, were treated off-label with sodium oxybate in add-on therapy. We followed up the patients in order to assess treatment efficacy by means of clinical interview, visual analog scales (VAS) for frequency and severity, Clinical Global Impression (CGI) improvement scale and efficacy index, video-polysomnography and at-home actigraphy. Sodium oxybate intake was well tolerated and effective in reducing the number and intensity of RBD episodes; patients reported no new traumatic episodes. Results were confirmed by bed-partner reports, VAS, CGI improvement scale and efficacy index, and at-home actigraphic monitoring, the latter showing a trend of improvement in nocturnal sleep quality and reduction in motor activity, compared to the baseline. Nevertheless, video-polysomnography did not show a clear beneficial effect on sleep-related electromyographic parameters. Our cases suggest that sodium oxybate can be an effective add-on option for the treatment of idiopathic RBD refractory to conventional therapies. The lack of improvement of polysomnographic parameters suggests caution in considering only polysomnographic data as endpoints in the assessment of the efficacy of therapies for RBD, and that long-term home-based assessment seems a promising tool. Copyright © 2016 Elsevier B.V. All rights reserved.

Commercial off-the-Shelf (COTS) Refractory Material Evaluation

NASA Technical Reports Server (NTRS)

Calle, Luz Marina; Kolody, Mark R.; Curran, Jerome P.; Back, Teddy; Hintze, Paul E.; Parlier, Christopher R.; Sampson, Jeffrey W.; Perusich, Stephen; Bucherl, Cori

2009-01-01

Fondu Fyre (FF) is currently the only refractory material qualified for use in the flame trench at KSC's Shuttle Launch Pads 39A and 39B. However, the material is not used as it was qualified and has undergone increasingly frequent and severe degradation due to the launch blasts. This degradation is costly as well as dangerous for launch infrastructure, crew and vehicle. FF is applied at the pad via the gunnite process, where wetted refractory material is sprayed onto a steel grid mounted on a support structure. The water content in this process can be manually adjusted by operators, causing distinct visual and physical discrepancies among repair areas. Since the application process is unlikely to change for new refractory materials, it is important to understand the effects of water content on commercial off-the-shelf (COTS) refractory materials. The purpose of this study was to evaluate the performance of the FF with respect to various water contents as well as heat treatments, to simulate aging and exposure to the blast. Initial results indicated that different water contents and heat treatments result in distinct differences in crushing strength, apparent porosity and bulk density. However, water content became an insignificant factor in both crush strength and porosity when FF was cured to at least 1500 deg. Additionally, inspection of the material's surface microstructure by scanning electron microscopy indicated distinguishable characteristics for different heat treatment levels. Results from this study will help guide future studies on the development and identification of new refractory materials.

Single-Session CT-Guided Percutaneous Microwave Ablation of Bilateral Adrenal Gland Hyperplasia Due to Ectopic ACTH Syndrome

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

Sarma, Asha, E-mail: ashasarma@gmail.com; Shyn, Paul B., E-mail: pshyn@partners.org; Vivian, Mark A.

Bilateral adrenalectomy is currently the only available treatment for adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome (ectopic ACTH syndrome) that is refractory to pharmacologic therapy. We describe two patients with refractory ectopic ACTH syndrome who were treated with CT-guided percutaneous microwave ablation of both hyperplastic adrenal glands in a single session: One was not a surgical candidate, and the other had undergone unsuccessful surgery. Following the procedure, both patients achieved substantial decreases in serum cortisol, symptomatic improvement, and decreased anti-hypertensive medication requirements.

Ketogenic diet in the treatment of refractory continuous spikes and waves during slow sleep.

PubMed

Nikanorova, Marina; Miranda, Maria J; Atkins, Mary; Sahlholdt, Lene

2009-05-01

To evaluate the effect of the ketogenic diet on electroclinical characteristics and cognitive function in children with continuous spikes and waves during slow sleep (CSWS). Five children (four boys, one girl) aged between 8 and 13 years with CSWS refractory to conventional antiepileptic drugs (AEDs), including levetiracetam, and steroids were included. The prospective electroclinical assessment was performed prior to the ketogenic diet and once every 6 months post initiation during the 2-year period. All children underwent neuropsychological testing prior to the ketogenic diet and four of the children again 12 months after the diet's introduction. In case 4 the testing has been performed after 7 months and the diet was withdrawn after 9 months because of the lack of efficacy and the parent's wishes. In two patients the cognitive functions were also evaluated after 24 months since the diet's initiation. During the period on the ketogenic diet the concomitant AED treatment was unchanged. Electrographic evaluation after 24 months on the ketogenic diet showed CSWS resolution in one patient, mild decrease of the spike-wave index in one, and lack of response in three patients. The ketogenic diet did not influence the neuropsychological outcome, and intelligence quotient (IQ) scores remained low at the end of the follow-up period. However, in two patients an improvement in attention and behavior was demonstrated. This is the first study evaluating the efficacy of the ketogenic diet in children with CSWS. Five presented cases were refractory to AEDs and steroids. Only one case responded with complete CSWS disappearance; in one the effect of the ketogenic diet was partial and intermittent, whereas in three patients no response has been observed. These results show that the ketogenic diet did not appear to influence the neuropsychological outcome; however, the absence of a control group makes it impossible to conclude with certainty.

Locoregional mitomycin C injection for esophageal stricture after endoscopic submucosal dissection.

PubMed

Machida, H; Tominaga, K; Minamino, H; Sugimori, S; Okazaki, H; Yamagami, H; Tanigawa, T; Watanabe, K; Watanabe, T; Fujiwara, Y; Arakawa, T

2012-06-01

This prospective study aimed to evaluate the feasibility and safety of locoregional mitomycin C (MMC) injection to treat refractory esophageal strictures after endoscopic submucosal dissection (ESD) for superficial esophageal carcinoma. Patients with dysphagia and strictures that were refractory to repeated endoscopic balloon dilation (EBD) were eligible. After EBD, MMC was injected into the dilated site. Between June 2009 and August 2010, five patients were recruited. The treatment was performed once in two patients and twice in three patients with recurrent dysphagia or restenosis. In all patients, passing a standard endoscope through the site was easy and the dysphagia grade improved (grade 3→1 in 3 patients, grade 4→2 in 2 patients). No serious complications were noted. During the observation period of 4.8 months, neither recurrent dysphagia nor re-stricture appeared in any of the patients. The combination of locoregional MMC injections and EBD is feasible and safe for the treatment of esophageal strictures after ESD.Recently, endoscopic submucosal dissection (ESD) has been developed and accepted as a new endoscopic treatment for gastrointestinal tumors. ESD is a promising treatment for superficial esophageal carcinoma (SEC), and it has a reliable en bloc resection rate. However, the application of ESD for widespread lesions is challenging because of the high risk of the development of severe strictures, which lead to a low quality of life after ESD. Although endoscopic balloon dilation (EBD) is effective for benign strictures, it needs to be performed frequently until the dysphagia disappears 1. Mitomycin C (MMC), which is a chemotherapeutic agent derived from some Streptomyces species 2, reduces scar formation when topically applied to a surgical lesion. MMC has been applied to treat strictures in a variety of anatomical locations, including a variety of organs 3. The aim of this study was to prospectively evaluate both the feasibility and the safety of locoregional MMC injection therapy in patients with refractory esophageal strictures after ESD for SEC. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of Different Structural Materials on Neutronic Performance of a Hybrid Reactor

NASA Astrophysics Data System (ADS)

Übeyli, Mustafa; Tel, Eyyüp

2003-06-01

Selection of structural material for a fusion-fission (hybrid) reactor is very important by taking into account of neutronic performance of the blanket. Refractory metals and alloys have much higher operating temperatures and neutron wall load (NWL) capabilities than low activation materials (ferritic/martensitic steels, vanadium alloys and SiC/SiC composites) and austenitic stainless steels. In this study, effect of primary candidate refractory alloys, namely, W-5Re, T111, TZM and Nb-1Zr on neutronic performance of the hybrid reactor was investigated. Neutron transport calculations were conducted with the help of SCALE 4.3 System by solving the Boltzmann transport equation with code XSDRNPM. Among the investigated structural materials, tantalum had the worst performance due to the fact that it has higher neutron absorption cross section than others. And W-5Re and TZM having similar results showed the best performance.

MicroRNA Expression-Based Model Indicates Event-Free Survival in Pediatric Acute Myeloid Leukemia

PubMed Central

Lim, Emilia L.; Trinh, Diane L.; Ries, Rhonda E.; Wang, Jim; Gerbing, Robert B.; Ma, Yussanne; Topham, James; Hughes, Maya; Pleasance, Erin; Mungall, Andrew J.; Moore, Richard; Zhao, Yongjun; Aplenc, Richard; Sung, Lillian; Kolb, E. Anders; Gamis, Alan; Smith, Malcolm; Gerhard, Daniela S.; Alonzo, Todd A.; Meshinchi, Soheil; Marra, Marco A.

2017-01-01

Purpose Children with acute myeloid leukemia (AML) whose disease is refractory to standard induction chemotherapy therapy or who experience relapse after initial response have dismal outcomes. We sought to comprehensively profile pediatric AML microRNA (miRNA) samples to identify dysregulated genes and assess the utility of miRNAs for improved outcome prediction. Patients and Methods To identify miRNA biomarkers that are associated with treatment failure, we performed a comprehensive sequence-based characterization of the pediatric AML miRNA landscape. miRNA sequencing was performed on 1,362 samples—1,303 primary, 22 refractory, and 37 relapse samples. One hundred sixty-four matched samples—127 primary and 37 relapse samples—were analyzed by using RNA sequencing. Results By using penalized lasso Cox proportional hazards regression, we identified 36 miRNAs the expression levels at diagnosis of which were highly associated with event-free survival. Combined expression of the 36 miRNAs was used to create a novel miRNA-based risk classification scheme (AMLmiR36). This new miRNA-based risk classifier identifies those patients who are at high risk (hazard ratio, 2.830; P ≤ .001) or low risk (hazard ratio, 0.323; P ≤ .001) of experiencing treatment failure, independent of conventional karyotype or mutation status. The performance of AMLmiR36 was independently assessed by using 878 patients from two different clinical trials (AAML0531 and AAML1031). Our analysis also revealed that miR-106a-363 was abundantly expressed in relapse and refractory samples, and several candidate targets of miR-106a-5p were involved in oxidative phosphorylation, a process that is suppressed in treatment-resistant leukemic cells. Conclusion To assess the utility of miRNAs for outcome prediction in patients with pediatric AML, we designed and validated a miRNA-based risk classification scheme. We also hypothesized that the abundant expression of miR-106a could increase treatment resistance via modulation of genes that are involved in oxidative phosphorylation. PMID:29068783

Efficacy and Safety of Ibrutinib in Indian Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma: Cases from a Named Patient Program.

PubMed

Agarwal, Mohan B; Bhurani, Dinesh; Shah, Chirag; Sood, Nitin; Singhal, Manish; Kamat, Anil; Chezhian, Subash; Mishra, Suryaprakash; Nagrale, Dinesh

2017-01-01

This named patient program evaluated the safety and efficacy of ibrutinib, a selective inhibitor of Bruton's tyrosine kinase in Indian patients with relapsed/refractory chronic lymphocytic leukemia (CLL, with/without chromosome 17 deletion [del17p]) and mantle cell lymphoma (MCL). The eight enrolled patients (relapsed/refractory CLL: n = 6 [4/6 patients with del17p] and relapsed/refractory MCL: n = 2) had median age of 55 years (range, 52-60) and had received a median of 3 (CLL patients) and 4 (MCL patients) prior therapies. Patients received once-daily dose of ibrutinib (420 mg: CLL, 560 mg: MCL). In CLL patients, the median time to response was 3 months (range, 0.5-7) and five of six patients had partial response (PR) whereas one achieved complete response (CR). Median time on treatment was 11.5 months (range, 8-14); five patients continued treatment and one was recommended stem cell transplantation (SCT). Of the two MCL patients, one achieved PR and one showed CR and advanced to SCT. In CLL patients, the median (range) hemoglobin level improved from 9.8 g/dL (7.2-11) at baseline to 12.0 g/dL (9.5-13.2) and median (range) platelet count improved from 150,000 cells/μL (21,000-195,000) at baseline to 190,350 cells/μL (130,000-394,000) at the time of analysis (July 2016). Most adverse events (AEs) reported were infections ( n = 2). No Grade 3-4 or serious AEs, dose reductions, or treatment discontinuation due to AEs were reported. In this first real-world experience in Indian patients, ibrutinib demonstrated therapeutic efficacy in relapsed/refractory CLL (with/without del17p) and MCL. Safety results were consistent with the current known profile of ibrutinib.

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.

Iterative Structural and Functional Synergistic Resolution Recovery (iSFS-RR) Applied to PET-MR Images in Epilepsy

NASA Astrophysics Data System (ADS)

Silva-Rodríguez, J.; Cortés, J.; Rodríguez-Osorio, X.; López-Urdaneta, J.; Pardo-Montero, J.; Aguiar, P.; Tsoumpas, C.

2016-10-01

Structural Functional Synergistic Resolution Recovery (SFS-RR) is a technique that uses supplementary structural information from MR or CT to improve the spatial resolution of PET or SPECT images. This wavelet-based method may have a potential impact on the clinical decision-making of brain focal disorders such as refractory epilepsy, since it can produce images with better quantitative accuracy and enhanced detectability. In this work, a method for the iterative application of SFS-RR (iSFS-RR) was firstly developed and optimized in terms of convergence and input voxel size, and the corrected images were used for the diagnosis of 18 patients with refractory epilepsy. To this end, PET/MR images were clinically evaluated through visual inspection, atlas-based asymmetry indices (AIs) and SPM (Statistical Parametric Mapping) analysis, using uncorrected images and images corrected with SFS-RR and iSFS-RR. Our results showed that the sensitivity can be increased from 78% for uncorrected images, to 84% for SFS-RR and 94% for the proposed iSFS-RR. Thus, the proposed methodology has demonstrated the potential to improve the management of refractory epilepsy patients in the clinical routine.

Excimer laser therapy and narrowband ultraviolet B therapy for exfoliative cheilitis.

PubMed

Bhatia, Bhavnit K; Bahr, Brooks A; Murase, Jenny E

2015-06-01

Exfoliative cheilitis is a condition of unknown etiology characterized by hyperkeratosis and scaling of vermilion epithelium with cyclic desquamation. It remains largely refractory to treatment, including corticosteroid therapy, antibiotics, antifungals, and immunosuppressants. We sought to evaluate the safety and efficacy of excimer laser therapy and narrowband ultraviolet B therapy in female patients with refractory exfoliative cheilitis. We reviewed the medical records of two female patients who had been treated unsuccessfully for exfoliative cheilitis. We implemented excimer laser therapy, followed by hand-held narrowband UVB treatments for maintenance therapy, and followed them for clinical improvement and adverse effects. Both patients experienced significant clinical improvement with minimal adverse effects with excimer laser therapy 600-700 mJ/cm 2 twice weekly for several months. The most common adverse effects were bleeding and burning, which occurred at higher doses. The hand-held narrowband UVB unit was also an effective maintenance tool. Limitations include small sample size and lack of standardization of starting dose and dose increments. Excimer laser therapy is a well-tolerated and effective treatment for refractory exfoliative cheilitis with twice weekly laser treatments of up to 700 mJ/cm 2 . Transitioning to the hand-held narrowband UVB device was also an effective maintenance strategy.

Effect of Continued Medical Therapy on Productivity Costs for Refractory Chronic Rhinosinusitis.

PubMed

Rudmik, Luke; Soler, Zachary M; Smith, Timothy L; Mace, Jess C; Schlosser, Rodney J; DeConde, Adam S

2015-11-01

It is estimated that lost productivity related to chronic rhinosinusitis (CRS) costs society in excess of $13 billion per year in the United States. Given this tremendous cost to society, it is important to evaluate the effect of current interventions on improving this productivity loss. To define the change in productivity costs in patients with refractory CRS who select continued medical therapy. Observational cohort study. Thirty-eight patients with a guideline-based diagnosis of CRS whose initial appropriate medical therapy failed were enrolled from 4 tertiary-level rhinology clinics. The study was conducted from December 6, 2010, to April 23, 2013, and data analysis was performed from December 6, 2010, to June 1, 2015. Continued medical therapy for CRS. The human capital approach was applied to quantify productivity costs. Absenteeism, presenteeism, and lost leisure time were quantified to define annual lost productive time, which was measured at enrollment (baseline) and at a minimum of 6 months after treatment. Lost productive time was monetized using the annual daily wage rates obtained from the 2012 US National Census and the 2013 US Department of Labor statistics. Thirty-eight patients with refractory CRS who selected continued medical therapy had a mean (SD) baseline annual productivity cost of $3464 ($4900) per patient. After continued medical therapy for a mean of 12.8 (4.8) months, productivity costs were $2730 ($3720) (before vs after continued medical therapy productivity cost, P = .74). Mean annual absenteeism was reduced from 5 (12) days to 2 (8) days (P = .02). Mean annual presenteeism (17 [27] days reduced to 15 [23] days; P = .93) and mean annual household days lost (7 [7] days reduced to 6 [6] days; P = .51) were maintained at baseline levels. There were no significant differences in productivity outcomes based on endoscopy, the 22-item Sinonasal Outcome Test score, age, or polyp status (all P ≥ .11). Patients with refractory CRS often make treatment decisions based on the degree of quality-of-life and productivity impairment. Outcomes from this study suggest that productivity in patients with refractory CRS who have minor reductions in baseline productivity can remain stable with continued medical therapy. Physicians can use this information to inform appropriate patients with CRS of their expected outcomes from continued medical therapy.

Thermostructural applications of heat pipes for cooling leading edges of high-speed aerospace vehicles

NASA Technical Reports Server (NTRS)

Camarda, Charles J.; Glass, David E.

1992-01-01

Heat pipes have been considered for use on wing leading edge for over 20 years. Early concepts envisioned metal heat pipes cooling a metallic leading edge. Several superalloy/sodium heat pipes were fabricated and successfully tested for wing leading edge cooling. Results of radiant heat and aerothermal testing indicate the feasibility of using heat pipes to cool the stagnation region of shuttle-type space transportation systems. The test model withstood a total seven radiant heating tests, eight aerothermal tests, and twenty-seven supplemental radiant heating tests. Cold-wall heating rates ranged from 21 to 57 Btu/sq ft-s and maximum operating temperatures ranged from 1090 to 1520 F. Follow-on studies investigated the application of heat pipes to cool the stagnation regions of single-stage-to-orbit and advanced shuttle vehicles. Results of those studies indicate that a 'D-shaped' structural design can reduce the mass of the heat-pipe concept by over 44 percent compared to a circular heat-pipe geometry. Simple analytical models for heat-pipe startup from the frozen state (working fluid initially frozen) were adequate to approximate transient, startup, and steady-state heat-pipe performance. Improvement in analysis methods has resulted in the development of a finite-element analysis technique to predict heat-pipe startup from the frozen state. However, current requirements of light-weight design and reliability suggest that metallic heat pipes embedded in a refractory composite material should be used. This concept is the concept presently being evaluated for NASP. A refractory-composite/heat-pipe-cooled wing leading edge is currently being considered for the National Aero-Space Plane (NASP). This concept uses high-temperature refractory-metal/lithium heat pipes embedded within a refractory-composite structure and is significantly lighter than an actively cooled wing leading edge because it eliminates the need for active cooling during ascent and descent. Since the NASP vehicle uses cryogenic hydrogen to cool structural components and then burns this fuel in the combustor, hydrogen necessary for descent cooling only, when the vehicle is unpowered, is considered to be a weight penalty. Details of the design of the refractory-composite/heat-pipe-cooled wing leading edge are currently being investigated. Issues such as thermal contact resistance and thermal stress are also being investigated.

Thermostructural applications of heat pipes for cooling leading edges of high-speed aerospace vehicles

NASA Astrophysics Data System (ADS)

Camarda, Charles J.; Glass, David E.

1992-10-01

Heat pipes have been considered for use on wing leading edge for over 20 years. Early concepts envisioned metal heat pipes cooling a metallic leading edge. Several superalloy/sodium heat pipes were fabricated and successfully tested for wing leading edge cooling. Results of radiant heat and aerothermal testing indicate the feasibility of using heat pipes to cool the stagnation region of shuttle-type space transportation systems. The test model withstood a total seven radiant heating tests, eight aerothermal tests, and twenty-seven supplemental radiant heating tests. Cold-wall heating rates ranged from 21 to 57 Btu/sq ft-s and maximum operating temperatures ranged from 1090 to 1520 F. Follow-on studies investigated the application of heat pipes to cool the stagnation regions of single-stage-to-orbit and advanced shuttle vehicles. Results of those studies indicate that a 'D-shaped' structural design can reduce the mass of the heat-pipe concept by over 44 percent compared to a circular heat-pipe geometry. Simple analytical models for heat-pipe startup from the frozen state (working fluid initially frozen) were adequate to approximate transient, startup, and steady-state heat-pipe performance. Improvement in analysis methods has resulted in the development of a finite-element analysis technique to predict heat-pipe startup from the frozen state. However, current requirements of light-weight design and reliability suggest that metallic heat pipes embedded in a refractory composite material should be used. This concept is the concept presently being evaluated for NASP. A refractory-composite/heat-pipe-cooled wing leading edge is currently being considered for the National Aero-Space Plane (NASP). This concept uses high-temperature refractory-metal/lithium heat pipes embedded within a refractory-composite structure and is significantly lighter than an actively cooled wing leading edge because it eliminates the need for active cooling during ascent and descent. Since the NASP vehicle uses cryogenic hydrogen to cool structural components and then burns this fuel in the combustor, hydrogen necessary for descent cooling only, when the vehicle is unpowered, is considered to be a weight penalty. Details of the design of the refractory-composite/heat-pipe-cooled wing leading edge are currently being investigated. Issues such as thermal contact resistance and thermal stress are also being investigated.

Penetration and Effectiveness of Micronized Copper in Refractory Wood Species

PubMed Central

Civardi, Chiara; Van den Bulcke, Jan; Schubert, Mark; Michel, Elisabeth; Butron, Maria Isabel; Boone, Matthieu N.; Dierick, Manuel; Van Acker, Joris; Wick, Peter; Schwarze, Francis W. M. R.

2016-01-01

The North American wood decking market mostly relies on easily treatable Southern yellow pine (SYP), which is being impregnated with micronized copper (MC) wood preservatives since 2006. These formulations are composed of copper (Cu) carbonate particles (CuCO3·Cu(OH)2), with sizes ranging from 1 nm to 250 μm, according to manufacturers. MC-treated SYP wood is protected against decay by solubilized Cu2+ ions and unreacted CuCO3·Cu(OH)2 particles that successively release Cu2+ ions (reservoir effect). The wood species used for the European wood decking market differ from the North American SYP. One of the most common species is Norway spruce wood, which is poorly treatable i.e. refractory due to the anatomical properties, like pore size and structure, and chemical composition, like pit membrane components or presence of wood extractives. Therefore, MC formulations may not suitable for refractory wood species common in the European market, despite their good performance in SYP. We evaluated the penetration effectiveness of MC azole (MCA) in easily treatable Scots pine and in refractory Norway spruce wood. We assessed the effectiveness against the Cu-tolerant wood-destroying fungus Rhodonia placenta. Our findings show that MCA cannot easily penetrate refractory wood species and could not confirm the presence of a reservoir effect. PMID:27649315

Penetration and Effectiveness of Micronized Copper in Refractory Wood Species.

PubMed

Civardi, Chiara; Van den Bulcke, Jan; Schubert, Mark; Michel, Elisabeth; Butron, Maria Isabel; Boone, Matthieu N; Dierick, Manuel; Van Acker, Joris; Wick, Peter; Schwarze, Francis W M R

2016-01-01

The North American wood decking market mostly relies on easily treatable Southern yellow pine (SYP), which is being impregnated with micronized copper (MC) wood preservatives since 2006. These formulations are composed of copper (Cu) carbonate particles (CuCO3·Cu(OH)2), with sizes ranging from 1 nm to 250 μm, according to manufacturers. MC-treated SYP wood is protected against decay by solubilized Cu2+ ions and unreacted CuCO3·Cu(OH)2 particles that successively release Cu2+ ions (reservoir effect). The wood species used for the European wood decking market differ from the North American SYP. One of the most common species is Norway spruce wood, which is poorly treatable i.e. refractory due to the anatomical properties, like pore size and structure, and chemical composition, like pit membrane components or presence of wood extractives. Therefore, MC formulations may not suitable for refractory wood species common in the European market, despite their good performance in SYP. We evaluated the penetration effectiveness of MC azole (MCA) in easily treatable Scots pine and in refractory Norway spruce wood. We assessed the effectiveness against the Cu-tolerant wood-destroying fungus Rhodonia placenta. Our findings show that MCA cannot easily penetrate refractory wood species and could not confirm the presence of a reservoir effect.

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.

Covered metal stent or multiple plastic stents for refractory pancreatic ductal strictures in chronic pancreatitis: a systematic review.

PubMed

Shen, Yonghua; Liu, Mingdong; Chen, Min; Li, Yunhong; Lu, Ying; Zou, Xiaoping

2014-01-01

Refractory chronic pancreatitis has been proposed as a challenge for endoscopists following routine single plastic stenting. However, data on the efficacy and safety of further endoscopic stenting are still controversial. The current systematic review aimed to assess the efficacy and safety of placement of fully covered self-expandable metal stent (FCSEMS) and multiple plastic stents. Databases including MEDLINE, EMBASE, the Cochrane Library, CBM, CNKI, VIP, and WANFANG Database were used to search relevant trials. Published studies were assessed by using well-defined inclusion and exclusion criteria. The process was independently performed by two investigators. A total of 5 studies provided data of 80 patients. Forest plots and publication bias were not carried out because few studies were relevant and screened studies were all case series. The technical success rate was 100% both in placement of FCSEMS and multiple plastic stents. The functional success rate after placement of FCSEMS was 100%, followed by multiple plastic stents (94.7%). Complications occurred 26.2% after FCSEMS placement, which was not described in detail in multiple plastic stents. The stent migration rate was 8.2% for FCSEMS and 10.5% for multiple plastic stents. Reintervention rate was 9.8% for FCSEMS and 15.8% for multiple plastic stents. Pain improvement rate was 85.2% for FCSEMS and 84.2% for multiple plastic stents. FCSEMS appeared to be no significant difference with multiple plastic stents in treatment of refractory chronic pancreatitis. We need to develop more investigations. Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Management of Transjugular Intrahepatic Portosystemic Shunt (TIPS)-associated Refractory Hepatic Encephalopathy by Shunt Reduction Using the Parallel Technique: Outcomes of a Retrospective Case Series

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

Cookson, Daniel T., E-mail: danielthomascookson@yahoo.co.uk; Zaman, Zubayr; Gordon-Smith, James

2011-02-15

Purpose: To investigate the reproducibility and technical and clinical success of the parallel technique of transjugular intrahepatic portosystemic shunt (TIPS) reduction in the management of refractory hepatic encephalopathy (HE). Materials and Methods: A 10-mm-diameter self-expanding stent graft and a 5-6-mm-diameter balloon-expandable stent were placed in parallel inside the existing TIPS in 8 patients via a dual unilateral transjugular approach. Changes in portosystemic pressure gradient and HE grade were used as primary end points. Results: TIPS reduction was technically successful in all patients. Mean {+-} standard deviation portosystemic pressure gradient before and after shunt reduction was 4.9 {+-} 3.6 mmHg (range,more » 0-12 mmHg) and 10.5 {+-} 3.9 mmHg (range, 6-18 mmHg). Duration of follow-up was 137 {+-} 117.8 days (range, 18-326 days). Clinical improvement of HE occurred in 5 patients (62.5%) with resolution of HE in 4 patients (50%). Single episodes of recurrent gastrointestinal hemorrhage occurred in 3 patients (37.5%). These were self-limiting in 2 cases and successfully managed in 1 case by correction of coagulopathy and blood transfusion. Two of these patients (25%) died, one each of renal failure and hepatorenal failure. Conclusion: The parallel technique of TIPS reduction is reproducible and has a high technical success rate. A dual unilateral transjugular approach is advantageous when performing this procedure. The parallel technique allows repeat bidirectional TIPS adjustment and may be of significant clinical benefit in the management of refractory HE.« less

A case of severe refractory chronic urticaria: a novel method for evaluation and treatment.

PubMed

Otto, Hans F; Calabria, Christopher W

2009-01-01

With cholinergic urticaria (ChU), the ultimate diagnosis often depends on the demonstration of characteristic urticaria by appropriate provocation. Several treatment options may be helpful but traditional options (antihistamines, leukotriene inhibitors, and immunosuppressives) may be exhausted by the refractory ChU patient. Here, we describe such a case. Demonstration of immediate hypersensitivity to autologous sweat skin testing (ASwST) may provide a rationale for use of omalizumab (Xolair, Genentech Novartis, South San Francisco, CA). Patients with severe ChU may have difficulty producing sufficient quantities of sweat for ASwST given that the very effort that produces the sample exacerbates ChU. Generation of sweat by iontophoresis with pilocarpine nitrate can be performed at many large medical centers. The procedure is simple, safe, and produces varying amounts of sweat depending on the individual. This sweat can then be used for ASwST. Our patient had a positive ASwST with appropriate positive and negative controls. Our testing methods were validated by negative ASwST, saline control, and positive histamine control in a nonatopic, nonurticarial control patient. By the patient's second injection of omalizumab, her quality of life score was significantly improved, as were her daily medication scores and exercise tolerance. We describe the first case of a patient with severe refractory ChU who had a positive ASwST by a novel collection method who has been successfully treated with omalizumab. We present a novel tool for the evaluation and demonstration of sweat-specific IgE in ChU patients who are unable to provide sweat by more traditional means.

Tensile Behavior of Electron Beam-Welded and Post-Weld Vacuum-Annealed Nb-10% Hf-1% Ti Refractory Alloy Weldments

NASA Astrophysics Data System (ADS)

Anil Kumar, V.; Gupta, R. K.; Venkateswaran, T.; Ram Kumar, P.

2018-02-01

Nb-10% Hf-1% Ti refractory alloy is a high performance material extensively used for high temperature applications. Electron beam welding is one of the most widely used techniques to join refractory and reactive alloys. Bigger sizes of nozzles for rocket propulsion applications can be either made through deep drawing and flow turning route or by roll bending and welding route both using sheets/plates as input material for fabrication. The latter is a more economical option for mass production of the hardware using such exotic and expensive alloys. In view of this, both as-welded (AW) coupon and weld plus post-weld vacuum-annealed (AW + VA) coupon have been prepared to study their mechanical behavior. It has been observed that tensile strength and ductility have not been reduced in both these conditions vis-à-vis the base metal, confirming weld efficiency of the alloy to be 100%. Microhardness is found to be 150-160 VHN in the base metal and 200-225 VHN in the weld fusion zone in AW condition, which became uniform (145-155 VHN) throughout the weldment in AW + VA condition. Microstructure of the weldment in AW condition is found to be consisting of grains solidified by epitaxial mode from base metal toward the weld centre. In AW + VA condition, improvement in tensile elongation is observed, which is found to be due to the presence of homogenized grains/more uniform microstructure near the heat-affected zone as compared to the steep gradient in grain size in different zones in the weld in AW condition.

Ultrasound-guided platelet-rich plasma injection for distal biceps tendinopathy

PubMed Central

Bell, Simon N; Connell, David; Coghlan, Jennifer A

2015-01-01

Background Distal biceps tendinopathy is an uncommon cause of elbow pain. The optimum treatment for cases refractory to conservative treatment is unclear. Platelet-rich plasma has been used successfully for other tendinopathies around the elbow. Methods Six patients with clinical and radiological evidence of distal biceps tendinopathy underwent ultrasound-guided platelet-rich plasma (PRP) injection. Clinical examination findings, visual analogue score (VAS) for pain and Mayo Elbow Performance scores were recorded. Results The Mayo Elbow Performance Score improved from 68.3 (range 65 to 85) (fair function) to 95 (range 85 to 100) (excellent function). The VAS at rest improved from a mean of 2.25 (range 2 to 5) pre-injection to 0. The VAS with movement improved from a mean of 7.25 (range 5 to 8) pre-injection to 1.3 (range 0 to 2). No complications were noted. Discussion Ultrasound-guided PRP injection appears to be a safe and effective treatment for recalcitrant cases of distal biceps tendinopathy. Further investigation with a randomized controlled trial is needed to fully assess its efficacy. PMID:27582965

Development and Implementation of the Casting of Rods Made of Refractory Cast Alloys

NASA Astrophysics Data System (ADS)

Kabanov, I. V.; Urin, S. L.; Ivanyuk, A. S.; Nesterov, A. N.; Bogdanov, S. V.

2017-12-01

The problems of the production of a so-called casting rod blank made of a refractory casting alloy in the vacuum induction furnaces of AO Metallurgical Plant Electrostal are considered. A unique technology of casting and subsequent treatment of as-cast rod blanks made of refractory alloys is developed, tested, and optimized. As a result of the developed and performed measures for the production of metal products in the Consarc furnace, the ingot-to-product yield increases by 15% as compared to metal casting in an ISV-1.0 furnace. As a result, we have widened the range of cast alloy grades and are going to cast metals for the manufacture of blanks of other sizes and ranges of alloy an steel grades.

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

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.

Successful Treatment of Opioid-Refractory Cancer Pain with Short-Course, Low-Dose Ketamine.

PubMed

Waldfogel, Julie M; Nesbit, Suzanne; Cohen, Steven P; Dy, Sydney M

2016-12-01

Opioids remain the mainstay of treatment for severe cancer pain, but up to 20% of patients have persistent or refractory pain despite rapid and aggressive opioid titration, or develop refractory pain after long-term opioid use. In these scenarios, alternative agents and mechanisms for analgesia should be considered. This case report describes a 28-year-old man with metastatic pancreatic neuroendocrine cancer with severe, intractable pain despite high-dose opioids including methadone and a hydromorphone patient-controlled analgesia (PCA). After treatment with short-course, low-dose ketamine, his opioid requirements decreased by 99% and pain ratings by 50%, with the majority of this decrease occurring in the first 48 hours. As this patient's pain and opioid regimen escalated, he likely experienced some component of central sensitization and hyperalgesia. Administration of ketamine reduced opioid consumption by 99% and potentially "reset" neuronal hyperexcitability and reduced pain signaling, allowing for improved pain control.

Constraints on Galactic Cosmic-Ray Origins from Elemental and Isotopic Composition Measurements

NASA Technical Reports Server (NTRS)

Binns, W. R.; Christian, E. R.; Cummings, A. C.; deNolfo, G. A.; Israel, M. H.; Leske, R. A.; Mewaldt, R. A,; Stone, E. C.; vonRosevinge, T. T.; Wiedenbeck, M. E.

2013-01-01

The most recent measurements by the Cosmic Ray Isotope Spectrometer (CRIS) aboard the Advanced Composition Explorer (ACE) satellite of ultra-heavy cosmic ray isotopic and elemental abundances will be presented. A range of isotope and element ratios, most importantly Ne-22/Ne-20, Fe-58/Fe-56, and Ga-31/Ge -32 show that the composition is consistent with source material that is a mix of approx 80% ISM (with Solar System abundances) and 20% outflow/ejecta from massive stars. In addition, our data show that the ordering of refractory and volatile elements with atomic mass is greatly improved when compared to an approx 80%/20% mix rather than pure ISM, that the refractory and volatile elements have similar slopes, and that refractory elements are preferentially accelerated by a factor of approx 4. We conclude that these data are consistent with an OB association origin of GCRs.

Intravenous Foscarnet With Topical Cidofovir for Chronic Refractory Genital Herpes in a Patient With AIDS.

PubMed

Usoro, Agnes; Batts, Alfreda; Sarria, Juan C

2015-01-01

Few case reports have documented the use of topical cidofovir for refractory genital herpes simplex virus (HSV) ulcers in human immunodeficiency virus (HIV) infected patients. This drug formulation lacks a standardized concentration or even a procedural outline as to how it should be compounded. We aim to discuss the utilization of topical cidofovir in addition to presenting a procedural means of compounding it for treatment of refractory genital HSV ulcers. Our patient completed 21 days of intravenous foscarnet and 13 days of topical cidofovir with clinical improvement in the penile and scrotal ulcers. Genital herpes is a concern in patients with HIV because it generally manifests as a persistent infection. Physicians should be aware that when patients fail to respond to the conventional treatment regimens for genital HSV in a timely manner, other options are available, such as topical cidofovir as an adjuvant to systemic antivirals.

Feasibility Study for Casting of High Temperature Refractory Superalloy Composites

NASA Technical Reports Server (NTRS)

Lee, Jonathan A.

1998-01-01

Abstract This study investigated the feasibility of using conventional casting technique to fabricate refractory wires reinforced superalloy composites. These composites were being developed for advanced rocket engine turbine blades and other high temperature applications operating up to 2000 F. Several types of refractory metal wires such as W- Th, W-Re, Mo-Hf-C and W-HF-C reinforced waspaloy were experimentally cast and heat treated at 2000 F up to 48 hrs. Scanning electron microscope analysis was conducted in regions adjacent to the wire-matrix interface to determine the reaction zone and chemical compatibility resulting from material interdiffusion. It was concluded that fabrication using conventional casting may be feasible because the wire-matrix reaction zone thickness was comparable to similar composites produced by arc-sprayed monotape with hot isostatic pressing technique, Moreover, it was also found that the chemical compatibility could be improved significantly through a slight modification of the superalloy matrix compositions.

Management of refractory trigeminal neuralgia using extended duration pulsed radiofrequency application.

PubMed

Thapa, Deepak; Ahuja, Vanita; Dass, Christopher; Verma, Parul

2015-01-01

Trigeminal neuralgia (TN) produces incapacitating facial pain that reduces quality of life in patients. Thermal radiofrequency (RF) ablation of gasserian ganglion (GG) is associated with masseter weakness and unpleasant sensations along the distribution of the ablated nerve. Pulsed radiofrequency (PRF) of GG has minimal side effects but literature is inconclusive regarding its benefit in refractory TN. Increasing the duration of PRF application to 6 minutes in TN produced encouraging results. PRF application to the saphenous nerve for 8 minutes reported improved pain relief and patient satisfaction. We report successful management of two patients of classic TN, which were refractory to medical management and interventional nerve blocks. The lesion site were confirmed with motor and sensory stimulation through a 22 G, 10 cm RF needle with 5 mm active tip. Both the patients received four cycles of PRF at 42 °C with each cycle of 120 seconds (8 minutes). The visual analogue scale (VAS) in case 1 reduced from pre-block score of 80 to score 10 post-block, while in case 2 the VAS reduced from pre-block score of 85 to score 15 post-block. During follow up both the patients are now pain free with minimal dose of carbamazepine at 12 and 6 months respectively. We used PRF for longer duration (8 minutes) in these patients, which resulted in improved VAS and WHOQOL-BREF score in these patients. PRF of mandibular division of GG for extended duration provided long-term effective pain relief and quality of life in patients of refractory classic TN.

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

Interferon alpha-2a treatment for refractory Behcet uveitis in Korean patients.

PubMed

Lee, Ji Hwan; Lee, Christopher Seungkyu; Lee, Sung Chul

2018-02-20

To evaluate therapeutic outcomes of interferon alpha-2a (IFNα2a) treatment in patients with Behcet's disease who were refractory to immunosuppressive agents. This retrospective case series reviewed the medical records of 5 patients with refractory Behcet uveitis from January 2011 to February 2017. IFNα2a was administered at a dose of 3 million IU 3 times per week. Clinical response, relapse rate, and change of visual acuity were evaluated. The mean age of patients was 39.60 ± 9.21 years, and the median treatment duration was 6 months. Four of the 5 patients (80%) presented with responses to IFNα2a without any uveitis attack during the treatment period. The mean number of uveitis attacks/year per patient during the treatment was 0.40 ± 0.89. The mean log of the Minimum Angle of Resolution visual acuity improved from 1.44 ± 0.38 at baseline to 1.02 ± 0.58 at the final follow up. IFNα2a is an effective therapy for Behcet uveitis refractory to conventional immunosuppressants in Korean patients.

Seizures, refractory status epilepticus, and depolarization block as endogenous brain activities

NASA Astrophysics Data System (ADS)

El Houssaini, Kenza; Ivanov, Anton I.; Bernard, Christophe; Jirsa, Viktor K.

2015-01-01

Epilepsy, refractory status epilepticus, and depolarization block are pathological brain activities whose mechanisms are poorly understood. Using a generic mathematical model of seizure activity, we show that these activities coexist under certain conditions spanning the range of possible brain activities. We perform a detailed bifurcation analysis and predict strategies to escape from some of the pathological states. Experimental results using rodent data provide support of the model, highlighting the concept that these pathological activities belong to the endogenous repertoire of brain activities.

Sulfur tolerant highly durable CO.sub.2 sorbents

DOEpatents

Smirniotis, Panagiotis G [Cincinnati, OH; Lu, Hong [Urbana, IL

2012-02-14

A sorbent for the capture of carbon dioxide from a gas stream is provided, the sorbent containing calcium oxide (CaO) and at least one refractory dopant having a Tammann temperature greater than about 530.degree. C., wherein the refractory dopant enhances resistance to sintering, thereby conserving performance of the sorbent at temperatures of at least about 530.degree. C. Also provided are doped CaO sorbents for the capture of carbon dioxide in the presence of SO.sub.2.

Iodine-131 metaiodobenzylguanidine therapy for neuroblastoma: reports so far and future perspective.

PubMed

Kayano, Daiki; Kinuya, Seigo

2015-01-01

Neuroblastoma, which derives from neural crest, is the most common extracranial solid cancer in childhood. The tumors express the norepinephrine (NE) transporters on their cell membrane and take in metaiodobenzylguanidine (MIBG) via a NE transporter. Since iodine-131 (I-131) MIBG therapy was firstly reported, many trails of MIBG therapy in patients with neuroblastoma were performed. Though monotherapy with a low dose of I-131 MIBG could achieve high-probability pain reduction, the objective response was poor. In contrast, more than 12 mCi/kg I-131 MIBG administrations with or without hematopoietic cell transplantation (HCT) obtain relatively good responses in patients with refractory or relapsed neuroblastoma. The combination therapy with I-131 MIBG and other modalities such as nonmyeloablative chemotherapy and myeloablative chemotherapy with HCT improved the therapeutic response in patients with refractory or relapsed neuroblastoma. In addition, I-131 MIBG therapy incorporated in the induction therapy was proved to be feasible in patients with newly diagnosed neuroblastoma. To expand more the use of MIBG therapy for neuroblastoma, further studies will be needed especially in the use at an earlier stage from diagnosis, in the use with other radionuclide formations of MIBG, and in combined use with other therapeutic agents.

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.

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.

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

Carpenter, J.A.; Swanson, D.E; Chango, R.F.

Bethlehem Steel's Burns Harbor Div. operates two 89,000-cu ft blast furnaces, D and C, built in 1969 and 1972. These furnaces have been in the forefront of blast furnace performance since they were blown-in. To maintain a credible operation throughout the past 25 years their performance has been improved continuously. Production was increased approximately 3%/year while fuel rate decreased 1%/year. This presentation summarizes the early repairs, relines and improvements that have sustained and enhanced the furnace's performance. The fourth reline of both furnaces will be discussed in detail. As part of the 1991 reline of D furnace its lines weremore » improved and modern penstocks installed. The bosh, tuyere jacket, hearth jacket and both cast floors were replaced. The furnace now has a larger hearth making it easier to control and, liquid level is no longer a problem when pulling the wind to shut down. The new cast floor with its increased trough length has much improved separation of slag from iron and lowered refractory consumption. Since the cast floors on D furnace were changed, there has been a reduction in accidents and absenteeism. This may be related to the change in work practices on the new cast floors. The 1994 reline of C furnace incorporates those improvements made on D furnace in 1991. In addition, C furnace will have high-density cooling which is expected to double its campaign from 6 to 12 years, without interim repairs.« less

Experimental ammonia-free phosphate-bonded investments using Mg(H2PO4)2.

PubMed

Zhang, Z; Tamaki, Y; Miyazaki, T

2001-12-01

In previous study, we found that Mg(H2PO4)2 instead of NH4H2PO4 was available as a binder material for phosphate-bonded investments and possibly could be used to develop the phosphate-bonded investment without ammonia gas release. The purpose of the present study was to develop the experimental ammonia-free phosphate-bonded investments by investigating suitable refractories. Mg(H2PO4)2.nH2O and MgO were prepared as a binder. Cristobalite and quartz were selected as refractories. The power ratio of MgO/Mg(H2PO4)2.nH2O was set constant at 1.2 according to our previous findings. Fundamental properties of dental investment such as strength, manipulation and expansion were evaluated. Using cristobalite as the refractory material, further investigations were performed. The refractory/binder ratio was definitely effective. The increase of this ratio led to low mold strength and large mold expansion. The present findings suggested that C5 was desirable for dental investment.

Long-term Follow-up of a Case of Gold Shunt Surgery for Refractory Silicone Oil–induced Glaucoma

PubMed Central

Le, Ryan; Berger, Alan R.

2016-01-01

Purpose: To report the first case of gold shunt surgery for treatment of silicone oil–induced refractory glaucoma in a tertiary care academic center, with 5-year follow-up. Design: The study design is a case report. Participants: The participant was a patient who underwent gold shunt surgery. Methods: Institutional Research Ethics Board approval for the study was obtained. A diabetic patient was referred for refractory glaucoma with a history of proliferative diabetic retinal detachment, and surgery with silicone oil. She was uncontrolled on maximal medical therapy and following informed consent, gold shunt surgery was performed. Ocular outcomes and number of medications were reviewed over a 5-year period. Results: Following uncomplicated surgery, intraocular pressure was reduced from 41 to 14 mm Hg, and the number of medications was reduced from 4 to 1. Glaucomatous optic neuropathy remained stable. Conclusions: Gold shunt surgery in this challenging case of silicone oil refractory glaucoma provided long-term intraocular pressure control and reduced need for medication over a 5-year period. PMID:27253968

Evaluation of treatment with carboxymethylcellulose on chronic venous ulcers*

PubMed Central

Januário, Virginia; de Ávila, Dione Augusto; Penetra, Maria Alice; Sampaio, Ana Luisa Bittencourt; Noronha Neta, Maria Isabel; Cassia, Flavia de Freire; Carneiro, Sueli

2016-01-01

BACKGROUND: Among the chronic leg ulcers, venous ulcers are the most common and constitute a major burden to public health. Despite all technology available, some patients do not respond to established treatments. In our study, carboxymethylcellulose was tested in the treatment of refractory chronic venous ulcers. OBJECTIVE: To evaluate the efficacy of carboxymethylcellulose 20% on the healing of chronic venous ulcers refractory to conventional treatments. METHODS: This is an analytical, pre-experimental study. Thirty patients were included with refractory venous ulcers, and applied dressings with carboxymethylcellulose 20% for 20 weeks. The analysis was based on measurement of the area of ulcers, performed at the first visit and after the end of the treatment. RESULTS: There was a reduction of 3.9 cm2 of lesion area (p=0.0001), corresponding to 38.8% (p=0.0001). There was no interruption of treatment and no increase in lesion area in any patient. CONCLUSIONS: Carboxymethylcellulose 20% represents a low cost and effective therapeutic alternative for the treatment of refractory chronic venous ulcers. However, controlled studies are necessary to prove its efficacy. PMID:26982773

Pancreaticoportal Fistula and Disseminated Fat Necrosis After Revision of a Transjugular Intrahepatic Portosystemic Shunt

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

Klein, Seth J., E-mail: kleins@mir.wustl.edu; Saad, Nael; Korenblat, Kevin

A 59-year old man with alcohol related cirrhosis and portal hypertension was referred for transjugular intrahepatic portosystemic shunt (TIPS) to treat his refractory ascites. Ten years later, two sequential TIPS revisions were performed for shunt stenosis and recurrent ascites. After these revisions, he returned with increased serum pancreatic enzyme levels and disseminated superficial fat necrosis; an iatrogenic pancreaticoportal vein fistula caused by disruption of the pancreatic duct was suspected. The bare area of the TIPS was subsequently lined with a covered stent-graft, and serum enzyme levels returned to baseline. In the interval follow-up period, the patient has clinically improved.

A survey of Kaufman thruster cathodes.

NASA Technical Reports Server (NTRS)

Weigand, A. J.; Nakanishi, S.

1971-01-01

A survey is presented of various cathodes which have been developed and used in the Kaufman ion thruster. The electron-bombardment type ion source used in the thruster is briefly described. The general design, operating characteristics, and power requirements are shown for each type of cathode from the refractory metals used in 1960 to the plasma discharge hollow cathodes of today. A detailed discussion of the hollow cathode is given describing starting and cyclic operating characteristics as well as more fundamental design parameters. Tests to date show that the plasma hollow cathode is an efficient electron source with demonstrated durability over 10,000 hours and should offer further performance and life improvements.

Impact-Resistant Ceramic Coating

NASA Technical Reports Server (NTRS)

Wheeler, W. H.; Creedon, J. F.; Izu, Y. D.

1986-01-01

Refractory fibers more than double strength of coating. Impact strengths of ceramic coatings increase with increasing whisker content. Silicon carbide whiskers clearly produce largest increase, and improvement grows even more with high-temperature sintering. Coating also improves thermal and mechanical properties of electromagnetic components, mirrors, furnace linings, and ceramic parts of advanced internal-combustion engines.

Effect of powdered activated carbon technology on short-cut nitrogen removal for coal gasification wastewater.

PubMed

Zhao, Qian; Han, Hongjun; Xu, Chunyan; Zhuang, Haifeng; Fang, Fang; Zhang, Linghan

2013-08-01

A combined process consisting of a powdered activated carbon technology (PACT) and short-cut biological nitrogen removal reactor (SBNR) was developed to enhance the removal efficiency of the total nitrogen (TN) from the effluent of an upflow anaerobic sludge bed (UASB) reactor, which was used to treat coal gasification wastewater (CGW). The SBNR performance was improved with the increasing of COD and TP removal efficiency via PACT. The average removal efficiencies of COD and TP in PACT were respectively 85.80% and 90.30%. Meanwhile, the NH3-N to NO2-N conversion rate was achieved 86.89% in SBNR and the total nitrogen (TN) removal efficiency was 75.54%. In contrast, the AOB in SBNR was significantly inhibited without PACT or with poor performance of PACT in advance, which rendered the removal of TN. Furthermore, PAC was demonstrated to remove some refractory compounds, which therefore improved the biodegradability of the coal gasification wastewater. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Depression-Specific Outcomes After Treatment of Chronic Rhinosinusitis

PubMed Central

Schlosser, Rodney J.; Hyer, J. Madison; Smith, Timothy L.; Mace, Jess C.; Cortese, Bernadette M.; Uhde, Thomas W.; Rudmik, Luke; Soler, Zachary M.

2016-01-01

IMPORTANCE Depression is frequently undiagnosed in patients with chronic rhinosinusitis (CRS) and affects quality of life, productivity, and health care use. OBJECTIVE To examine depression-specific outcomes after medical or surgical treatment of CRS. DESIGN, SETTING, AND PARTICIPANTS A multi-institutional, prospective study of patients with refractory CRS treated at tertiary academic rhinology centers was performed from March 1, 2011, to November 1, 2015. Data analysis was performed from October 1, 2015, to November 1, 2015. INTERVENTIONS Patients self-selected to undergo continued medical management or endoscopic sinus surgery for refractory CRS. MAIN OUTCOMES AND MEASURES Patients completed the 22-item Sinonasal Outcome Test (SNOT22), Rhinosinusitis Disability Index (RSDI), Pittsburgh Sleep Quality Index (PSQI), and missed productivity and medication use questionnaires before and at least 6 months after treatment. Computed tomography and endoscopy scoring were performed with reviewers masked to patient-reported data. Depression-specific outcomes were recorded using the 2-item Patient Health Questionnaire (PHQ2). RESULTS Baseline data were available on 685 patients, with 167 (24.4%) having depression according to the PHQ2 scores. The mean (SD) age of the patients was 50.5 (15.0) years, and 332 (48.4%) were male. Revision surgery status was the only baseline factor associated with depression (53.9%vs 38.0%, P < .001). Patients with depression had worse baseline SNOT22 (mean, 64.5 vs 47.6), PSQI (mean, 12.8 vs 8.4), productivity (mean, 22.8 vs 5.2 days missed), and medication use scores for oral antibiotics (mean, 23.8 vs 14.8) and oral corticosteroids (mean, 17.8 vs 9.9) (P < .001 for all). Medical and surgical treatments had similar outcomes for patients with depression with mean improvement in the PHQ2 scores from 3.96 to 1.91 (P < .001), and 110 of 167 patients (65.9%) categorized as having depression at baseline were categorized as not having depression after treatment. Improvements in the PHQ2 scores were associated with improvements in the SNOT22, PSQI, oral antibiotic use, and productivity scores (P ≤ .001 for all). CONCLUSIONS AND RELEVANCE Depression is a common comorbidity in patients with CRS and affects numerous quality-of-life and health care outcomes. There are few objective baseline factors to aid physicians in identifying depression in patients with CRS. Medical and surgical treatments for CRS improve depression and related clinical outcomes. PMID:26967171

Antiviral Therapy in Steroid-refractory Ulcerative Colitis with Cytomegalovirus: Systematic Review and Meta-analysis.

PubMed

Shukla, Tushar; Singh, Siddharth; Loftus, Edward V; Bruining, David H; McCurdy, Jeffrey D

2015-11-01

The role of antiviral therapy in patients with ulcerative colitis (UC) with cytomegalovirus (CMV) remains unclear. We therefore performed a systematic review and meta-analysis to assess the association between antiviral therapy and the risk of colectomy. Multiple electronic databases were searched systematically through July 2014 for studies reporting the risk of colectomy in patients with UC with CMV stratified by treatment with antiviral agents. Colectomy rates were assessed for the overall cohort and stratified by corticosteroid (CS) refractoriness. We estimated summary odds ratios and 95% confidence intervals, using random-effects model, and used Grading of Recommendations Assessment, Development, and Evaluation criteria to appraise the quality of evidence. Fifteen observational studies (333 patients with UC with CMV, 43.2% treated with antiviral agents) were identified, of which 8 stratified patients according to CS-refractory disease (55.4% treated with antiviral agents). Antiviral therapy resulted in a significantly lower risk of colectomy in patients with CS-refractory disease (odds ratio, 0.20; 95% confidence interval, 0.08-0.49; I = 0%) but not in the overall population of patients with UC (odds ratio, 0.92; 95% confidence interval, 0.31-2.76; I = 65). The quality evidence was low. The results were stable when restricting the analysis to patients with a tissue diagnosis of CMV and studies that defined CS-refractory disease as a failure to respond to intravenous CS. Antiviral therapy may benefit a subgroup of patients with UC who are refractory to CS. Further prospective trials are required to confirm these findings.

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.

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

PubMed

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

2015-01-01

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

Treatment of Refractory Gastrointestinal Strictures With Mitomycin C: A Systematic Review.

PubMed

Rustagi, Tarun; Aslanian, Harry R; Laine, Loren

2015-01-01

Refractory benign gastrointestinal (GI) strictures represent a difficult management problem given the limited therapeutic interventions available. We performed a systematic review of all published cases using mitomycin C in the treatment of GI strictures. Searches of MEDLINE and Embase databases were performed to identify studies reporting application of mitomycin C for GI strictures. Review of titles/abstracts, full review of potentially relevant studies, and data abstraction were performed independently by 2 authors. Of 549 citations, 24 studies with 145 patients (74% pediatric and 26% adult) met inclusion criteria. Esophageal strictures were the most common (79%) site of refractory strictures treated with mitomycin C, with caustic injury the most common underlying etiology. The concentration (range, 0.1 to 2 mg/mL; median, 0.4 mg/mL), number of applications (range, 1 to 12; median, 1), duration of applications (range, 1 to 5; median, 2 min), and technique of application (cotton pledget, spray, injection, special catheters) varied among studies. Ninety-one patients (73%; children: 80%, adults: 59%) had a complete response; 26 (21%) had a partial response. Only 1 (0.7%) adverse event was reported: cutaneous sclerosis attributed to microperforation and mitomycin C extravastion after injection. Mean follow-up was 23 (4 to 60) months. Local mitomycin C application seems to be a safe and effective therapy for benign refractory GI strictures of varying etiology in both pediatric and adult populations. Although the results of this systematic review are highly encouraging, it should be considered investigational. Additional randomized trials and larger prospective studies are needed to confirm these results and to better define the optimal dose, concentration, duration and technique of mitomycin C application.

XEN-D0501, a Novel Transient Receptor Potential Vanilloid 1 Antagonist, Does Not Reduce Cough in Patients with Refractory Cough.

PubMed

Belvisi, Maria G; Birrell, Mark A; Wortley, Michael A; Maher, Sarah A; Satia, Imran; Badri, Huda; Holt, Kimberley; Round, Patrick; McGarvey, Lorcan; Ford, John; Smith, Jaclyn A

2017-11-15

Heightened cough responses to inhaled capsaicin, a transient receptor potential vanilloid 1 (TRPV1) agonist, are characteristic of patients with chronic cough. However, previously, a TRPV1 antagonist (SB-705498) failed to improve spontaneous cough frequency in these patients, despite small reductions in capsaicin-evoked cough. XEN-D0501 (a potent TRPV1 antagonist) was compared with SB-705498 in preclinical studies to establish whether an improved efficacy profile would support a further clinical trial of XEN-D0501 in refractory chronic cough. XEN-D0501 and SB-705498 were profiled against capsaicin in a sensory nerve activation assay and in vivo potency established against capsaicin-induced cough in the guinea pig. Twenty patients with refractory chronic cough participated in a double-blind, randomized, placebo-controlled crossover study evaluating the effect of 14 days of XEN-D0501 (oral, 4 mg twice daily) versus placebo on awake cough frequency (primary outcome), capsaicin-evoked cough, and patient-reported outcomes. XEN-D0501 was more efficacious and 1,000-fold more potent than SB-705498 at inhibiting capsaicin-induced depolarization of guinea pig and human isolated vagus nerve. In vivo XEN-D0501 completely inhibited capsaicin-induced cough, whereas 100 times more SB-705498 was required to achieve the same effect. In patients, XEN-D0501 substantially reduced maximal cough responses to capsaicin (mean change from baseline, XEN-D0501, -19.3 ± 16.4) coughs; placebo, -1.8 ± 5.8 coughs; P < 0.0001), but not spontaneous awake cough frequency (mean change from baseline, XEN-D0501, 6.7  ± 16.9 coughs/h; placebo, 0.4 ± 13.7 coughs/h; P = 0.41). XEN-D0501 demonstrated superior efficacy and potency in preclinical and clinical capsaicin challenge studies; despite this improved pharmacodynamic profile, spontaneous cough frequency did not improve, ruling out TRPV1 as an effective therapeutic target for refractory cough. Clinical trial registered with www.clinicaltrialsregister.eu (2014-000306-36).

“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.

Diverting Ileostomy for the Treatment of Severe, Refractory, Pediatric Inflammatory Bowel Disease.

PubMed

Maxwell, Elizabeth C; Dawany, Noor; Baldassano, Robert N; Mamula, Petar; Mattei, Peter; Albenberg, Lindsey; Kelsen, Judith R

2017-09-01

Diverting ileostomy is used as a temporizing therapy in patients with perianal Crohn disease; however, little data exist regarding its use for colonic disease. The primary aim of the present study was to determine the role of diversion in severe refractory colonic inflammatory bowel disease (IBD) in a pediatric population. Retrospective study of patients who underwent diverting ileostomy at The Children's Hospital of Philadelphia from 2000 to 2014 for the management of severe, refractory colonic IBD. Clinical variables were compared in the 1 year before ileostomy and 1 year after diversion. Surgical and disease outcomes including changes in diagnosis were reviewed through 2015. Twenty-four patients underwent diverting ileostomy for refractory colonic disease. Initial diagnoses were Crohn disease in 10 (42%), ulcerative colitis in 1 (4%), and IBD-unclassified in 13 patients (54%). Comparing data before and after surgery, there were statistically significant improvements in height and weight velocities, height velocity z score, blood transfusion requirement, hemoglobin, and hospitalization rates. Chronic steroid use decreased from 71% to 22%. At the conclusion of the study, 10 patients had undergone subsequent colectomy, 7 had successful bowel reanastomosis, and 7 remain diverted. Seven patients (29%) had a change in diagnosis. There were 13 surgical complications in 7 subjects, including prolapse reduction, stoma revision, and resection of ischemic bowel. In pediatric patients with refractory colonic IBD, diverting ileostomy can be a successful intervention to induce clinical stability. Importantly, diversion is a steroid-sparing therapy and allows additional time to clarify the diagnosis.

Efficacy of combination therapy of anti-TNF-α antibody infliximab and methotrexate in refractory entero-Behçet's disease.

PubMed

Iwata, Shigeru; Saito, Kazuyoshi; Yamaoka, Kunihiro; Tsujimura, Shizuyo; Nawata, Masao; Hanami, Kentaro; Tanaka, Yoshiya

2011-04-01

It is often difficult to manage refractory gastrointestinal tract complications of Behçet's disease (entero-BD) by conventional therapy. In this study, we assessed the short- and long-term efficacy and safety of the combination therapy of infliximab, an anti-tumor-necrosis-factor (TNF)-α antibody, and methotrexate in ten patients with refractory entero-BD refractory to conventional therapies. The short- (weeks) and long-term (by 2 years) effects of infliximab at 3-5 mg/kg body weight every 8 weeks on the clinical course and intestinal manifestations were assessed by abdominal computed tomography (CT) and colonoscopy. The primary endpoint was the rate of disappearance of ileocecal ulceration at 12 months of therapy. All patients showed improvement of gastrointestinal symptoms and disease-associated complications within 4 weeks. Furthermore, the rate of disappearance of ileocecal ulcerations was 50% (5/10 patients) at 6 months and 90% (9/10 patients) at 12 months, and, therefore 90% of patients were satisfied with the primary endpoint. Furthermore, corticosteroid dose was significantly reduced from 22.0 to 1.8 mg/day at 24 months. No severe adverse effects were observed during the 24 months of follow-up. We provide evidence for the rapid and excellent efficacy of infliximab in patients with refractory entero-BD and that the combination of infliximab and methotrexate brings about long-term alleviation of entero-BD and excellent tolerability.

Serendipity in Refractory Celiac Disease: Full Recovery of Duodenal Villi and Clinical Symptoms after Fecal Microbiota Transfer.

PubMed

van Beurden, Yvette H; van Gils, Tom; van Gils, Nienke A; Kassam, Zain; Mulder, Chris J J; Aparicio-Pagés, Nieves

2016-09-01

Treatment of refractory celiac disease type II (RCD II) and preventing the development of an enteropathy associated T-cell lymphoma in these patients is still difficult. In this case report, we describe a patient with RCD II who received fecal microbiota transfer as treatment for a recurrent Clostridium difficile infection, and remarkably showed a full recovery of duodenal villi and disappearance of celiac symptoms. This case suggests that altering the gut microbiota may hold promise in improving the clinical and histological consequences of celiac disease and/or RCD II.

Severe leptospirosis with multiple organ failure successfully treated by plasma exchange and high-volume hemofiltration.

PubMed

Bourquin, Vincent; Ponte, Belén; Hirschel, Bernard; Pugin, Jérôme; Martin, Pierre-Yves; Saudan, Patrick

2011-01-01

Background. Leptospirosis is a spirochetal zoonosis with complex clinical features including renal and liver failure. Case report. We report the case of a Swiss fisherman presenting with leptospirosis. After initial improvement, refractory septic shock and severe liver and kidney failure developed. The expected mortality was estimated at 90% with clinical scores. The patient underwent plasma exchanges and high-volume hemofiltration (HVHF) with complete recovery of hepatic and kidney functions. Discussion. Plasma exchanges and HVHF may confer survival benefit on patients with severe leptospirosis, refractory septic shock, and multiple-organ failure.

Processing and Properties Of Refractory Zirconium Diboride Composites For Use In High Temperature Applications

NASA Technical Reports Server (NTRS)

Stackpoole, Margaret; Gusman, M.; Ellerby, D.; Johnson, S. M.; Arnold, Jim (Technical Monitor)

2001-01-01

The Thermal Protection Materials and Systems Branch at NASA Ames Research Center is involved in the development of a class of refractory oxidation-resistant diboride composites termed Ultra High Temperature Ceramics or UHTCs. These composites have good high temperature properties making them candidate materials for thermal protection system (TPS) applications. The current research focuses on improving processing methods to develop more reliable composites with enhanced thermal and mechanical properties. This presentation will concentrate on the processing of ZrB2/SiC composites. Some preliminary mechanical properties and oxidation data will also be presented.

Development of wire drawing processes for refractory metal fibers

NASA Technical Reports Server (NTRS)

King, G. W.

1972-01-01

Fabrication schedules were developed for producing wire, 0.25 mm to 0.51 mm diameter, from the refractory metal alloys ASTAR-811C, B-88 and W-Hf-C. Tensile properties were evaluated at room temperature and up to 1204 C. Also, the stress rupture properties of the alloys at 1093 C were determined. W-Hf-C and B-88 were found to have the best mechanical properties on a strength to density basis. The fabrication schedules for producing wire from these two alloys were further improved with regards to the wire quality and material yield under the optimization of fabrication schedule.

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

PubMed Central

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

2013-01-01

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

High temperature refractory of MgCr.sub.2 O.sub.4 matrix and unstabilized ZrO.sub.2 particles

DOEpatents

Singh, Jitendra P.; James, Jawana J.; Picciolo, John J.

1987-01-01

A high chromia refractory composite has been developed with improved thermal shock resistance and containing about 5-30 wt. % of unstabilized ZrO.sub.2 having a temperature-dependent phase change resulting in large expansion mismatch between the ZrO.sub.2 and the chromia matrix which causes microcracks to form during cooling in the high chromia matrix. The particle size preferably is primarily between about 0.6-5 microns and particularly below about 3 microns with an average size in the order of 1.2-1.8 microns.

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

Management of reticular oral lichen planus patients with burning mouth syndrome-like oral symptoms: a pilot study.

PubMed

Adamo, Daniela; Mignogna, Michele Davide; Pecoraro, Giuseppe; Aria, Massimo; Fortuna, Giulio

2018-01-31

We sought to determine the efficacy of psychotropic drug in the management of BMS-like oral symptoms in patients with reticular oral lichen planus (R-OLP) refractory to conventional therapies, and its impact on anxious and depressive symptoms. We enrolled 28 cases of symptomatic R-OLP. The Numeric Rating Scale (NRS), the Total Pain Rating Index (T-PRI), the Hamilton rating scales for Depression (HAM-D) and Anxiety (HAM-A) were performed at baseline (time 0), after 2 months of topical clonazepam (time 1) and after 6 months of benzodiazepine and antidepressant drugs (time 2). R-OLP patients showed a statistically significant improvement in the NRS and T-PRI scores from time 0 [median: 9.0 (IQR: 7.2-10.0) and 10.5 (IQR: 7.0-13.0), respectively] to time 2 [(median: 2.0 (IQR: 2.0-3.0) (p < .001) and 3.0 (IQR: 2.0-4.7) (p < .001), respectively]. Similarly, the HAM-A and HAM-D scores showed an improvement from time 0 [(median: 15.0 (IQR: 10.2-17.8) and 13.0 (IQR: 12.0-15.0), respectively] to time 2 [median: 6.0 (IQR: 4.0-7.0) (p < .001) and 5.5 (IQR: 4.25-6.0) (p < .001), respectively]. Psychotropic drugs turned out to be effective in the management of BMS-like oral symptoms in R-OLP patients refractory to conventional immunosuppressive therapy, although in a long-term period.

Palliative Care Processes Embedded in the ICU Workflow May Reserve Palliative Care Teams for Refractory Cases.

PubMed

Mun, Eluned; Umbarger, Lillian; Ceria-Ulep, Clementina; Nakatsuka, Craig

2018-01-01

Palliative Care Teams have been shown to be instrumental in the early identification of multiple aspects of advanced care planning. Despite an increased number of services to meet the rising consultation demand, it is conceivable that the numbers of palliative care consultations generated from an ICU alone could become overwhelming for an existing palliative care team. Improve end-of-life care in the ICU by incorporating basic palliative care processes into the daily routine ICU workflow, thereby reserving the palliative care team for refractory situations. A structured, palliative care, quality-improvement program was implemented and evaluated in the ICU at Kaiser Permanente Medical Center in Hawaii. This included selecting trigger criteria, a care model, forming guidelines, and developing evaluation criteria. These included the early identification of the multiple features of advanced care planning, numbers of proactive ICU and palliative care family meetings, and changes in code status and treatment upon completion of either meeting. Early identification of Goals-of-Care, advance directives, and code status by the ICU staff led to a proactive ICU family meeting with resultant increases in changes in code status and treatment. The numbers of palliative care consultations also rose, but not significantly. Palliative care processes could be incorporated into a daily ICU workflow allowing for integration of aspects of advanced care planning to be identified in a systematic and proactive manner. This reserved the palliative care team for situations when palliative care efforts performed by the ICU staff were ineffective.

Langerhans cell histiocytosis: therapeutic strategy and outcome in a 30-year nationwide cohort of 1478 patients under 18 years of age.

PubMed

Rigaud, Charlotte; Barkaoui, Mohamed A; Thomas, Caroline; Bertrand, Yves; Lambilliotte, Anne; Miron, Jean; Aladjidi, Nathalie; Plat, Geneviève; Jeziorski, Eric; Galambrun, Claire; Mansuy, Ludovic; Lutz, Patrick; Deville, Anne; Armari-Alla, Corinne; Reguerre, Yves; Fraitag, Sylvie; Coulomb, Aurore; Gandemer, Virginie; Leboulanger, Nicolas; Moshous, Despina; Hoang-Xuan, Khe; Tazi, Abdellatif; Heritier, Sébastien; Emile, Jean-François; Donadieu, Jean

2016-09-01

The French national cohort of children with Langerhans cell histiocytosis (LCH) has included 1478 patients since it was established in 1983. LCH therapeutic strategies substantially changed in 1998, so we have divided the cohort into two 15-year periods. Starting in 1998, therapy duration increased from 6 to 12 months, repeated induction therapy was performed in cases showing a poor response to the first induction with vinblastine and steroids, and refractory disease in a risk organ (RO+) was treated with cladribine and cytarabine. A total of 483 (33%) patients were enrolled before 1998, and 995 (67%) after 1998. Five-year survival was 96·6% (95% confidence interval: 95·4-97·5%) overall, improving from 92% pre-1998 to 99% post-1998 (P < 0·001 adjusted to disease extent). This change was supported by an increase in 5-year survival from 60% to 92% in the RO+ group. Survival was particularly associated with cladribine and cytarabine among refractory RO+ patients. Disease reactivation was slightly less frequent after 1998, due to better enrolment of single-system patients, extended therapy duration, and more efficient second-line therapy. The crude rates of endocrine and neurological sequelae (the most frequent sequelae) appeared to improve over time, but this difference was not observed when the analysis was stratified by disease extent. © 2016 John Wiley & Sons Ltd.

Coal-oil gold agglomeration assisted flotation to recover gold from refractory ore

NASA Astrophysics Data System (ADS)

Otsuki, A.; Yue, C.

2017-07-01

This study aimed to investigate the applicability of coal-oil gold agglomeration (CGA) assisted flotation to recover gold from a refractory ore. The ore with the grade of 2-5 g/t was tested with the CGA-flotation process in six different size fractions from 38 to 300 urn using different collector types and dosages. In addition, the flotation without CGA was performed under the same condition for comparison. The results showed that the higher gold grade and recovery were achieved by applying the CGA-flotation, compared with the flotation without CGA. More than 20-60 times grade increase from the head grade was obtained with CGA-flotation. The elemental analysis of gold and sulphur explained their relationship with gold recovery. The results well indicated the applicability of CGA to upgrade the refractory gold ore.

Haptoglobin genotypes and refractory hypertension in type 2 diabetes mellitus patients.

PubMed

Wobeto, Vânia Pereira Albuquerque; Pinho, Paula da Cunha; Souza, José Roberto M; Zaccariotto, Tânia Regina; Zonati, Maria de Fátima

2011-10-01

It has been suggested that haptoglobin polymorphism may influence the pathogenesis of microvascular and macrovascular complications in diabetic patients. This cross sectional study was carried out to investigate the existence or not of an association between haptoglobin genotypes and prevalence of ischemic cardiovascular events (stable angina, unstable angina and acute myocardial infarction), systemic arterial hypertension, refractory hypertension, obesity and dyslipidemia in 120 type-2 diabetes mellitus patients followed up at Hospital de Clínicas da UNICAMP in Campinas, São Paulo state, southeastern Brazil. Haptoglobin genotyping was performed by allele-specific polymerase chain reactions. The frequencies of the haptoglobin genotypes were compared with the presence/absence of cardiovascular disease, systemic arterial hypertension, refractory hypertension, obesity and dyslipidemia; systolic and diastolic blood pressure measurements; plasma levels of glucose, cholesterol (total, high density lipoprotein-HDL and low density lipoprotein-LDL) and triglycerides; and serum creatinine levels. Although no association between haptoglobin genotype and the presence of cardiovascular disease could be identified, we found a significant excess of patients with Hp2-1 genotype among those with refractory hypertension, who also had higher systolic and diastolic blood pressure, and total and LDL cholesterol levels. Our results suggest that type-2 diabetes mellitus patients with the Hp2-1 genotype may have higher chances of developing refractory hypertension. Further studies in other diabetic populations are required to confirm these findings.

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.

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.

Ketamine for pain in adults and children with cancer: a systematic review and synthesis of the literature.

PubMed

Bredlau, Amy Lee; Thakur, Rajbala; Korones, David Nathan; Dworkin, Robert H

2013-10-01

Chronic cancer pain is often refractory and difficult to treat. Ketamine is a medication with evidence of efficacy in the treatment of chronic pain. This article presents a synthesis of the data on ketamine for refractory cancer pain in adults and children. There are five randomized, double-blind, controlled trials of ketamine use in cancer pain that demonstrate improvement in pain for some patients. There are six prospective, uncontrolled trials in cancer pain that also demonstrate improvement in pain scores for some patients. There are no randomized, controlled trials in children with cancer pain, although there are a few studies reflecting improved pain control with ketamine for children with cancer pain. Adverse events for adults on ketamine are most commonly somnolence, feelings of insobriety, nausea/vomiting, hallucinations, depersonalization/derealization, and drowsiness. However, when ketamine is combined with benzodiazepines, feelings of insobriety, hallucinations, and depersonalization/derealization are not reported. Children on ketamine have had few reported adverse effects, which include sedation, anorexia, urinary retention, and myoclonic movements. Recommended ketamine infusion dosages are from 0.05 to 0.5 mg/kg/h (intravenous or subcutaneous). Recommended oral dosages of ketamine are 0.2-0.5 mg/kg/dose two to three times daily with a maximum of 50 mg/dose three times daily. Despite limitations in the breadth and depth of data available, there is evidence that ketamine may be a viable option for treatment-refractory cancer pain. Wiley Periodicals, Inc.

Repeated B cell depletion in treatment of refractory systemic lupus erythematosus

PubMed Central

Ng, K P; Leandro, M J; Edwards, J C; Ehrenstein, M R; Cambridge, G; Isenberg, D A

2006-01-01

Objectives To report the clinical outcome and safety profile of repeated B cell depletion in seven patients with refractory systemic lupus erythematosus (SLE). Methods Since June 2000, seven patients with refractory SLE had repeated cycles of B cell depletion (18 cycles in total, up to three cycles per patient) because of disease relapse. The clinical response (assessed by the British Isles Lupus Activity Guide (BILAG) activity index), duration of B cell depletion, and adverse events in these patients was reviewed. Results Four patients (Nos 1, 2, 3, 6) had three cycles of treatment and three (Nos 4, 5, 7) had two cycles. Four of the seven patients (Nos 1, 3, 5, 6) improved. The mean global BILAG scores dropped from 15 to 6 at 5–7 months. The median duration of clinical response and B cell depletion was 13 months and 6 months, respectively. After the third cycle, 2/4 patients (Nos 1 and 2) improved. The median duration of clinical benefit was 12 months. Most patients tolerate re‐treatment very well. Conclusion Re‐treatment with B cell depletion of patients with severe SLE is safe and may be effective for 6–12 months on average. PMID:16269424

Retrospective Analysis of Nonepileptic Patients With Isolated Epileptiform Discharges Treated With Anticonvulsants.

PubMed

Swatzyna, Ronald J; Tarnow, Jay D; Proler, Meyer L; Roark, Alexandra J; MacInerney, Erin K; Kozlowski, Gerald P

2017-09-01

Many antiepileptic drugs (AEDs) have been tested on nonepileptic patients with a variety of diagnoses. The Food and Drug Administration has only approved certain AEDs for a small number of psychiatric conditions. There are few studies of nonepileptic patients that recommend an empirical trial of AEDs when isolated epileptiform discharges (IEDs) are identified in the electroencephalogram (EEG). However, no trials have been published. The purpose of this study is to evaluate the outcome of treating nonepileptic patients with AEDs when IEDs are present. Refractory cases were reviewed from a multidisciplinary practice whose EEG readings contained IEDs and were subsequently medicated with anticonvulsants by the clinic's psychiatrist. The psychiatrist's progress notes were assessed to determine the impact of adding anticonvulsants based on parent reports, teacher reports, and clinical observation. The final sample was composed of 76 refractory cases. Of the 76 patients treated with anticonvulsants, the majority were found to be improved in follow-up progress notes: 65 improved (85.53%), 6 unchanged (7.89%), and 5 more severe (6.58%). These observational findings suggest that further studies will be needed to show that IEDs may predict positive treatment outcome to anticonvulsant medication and act as a step toward an evidence-based treatment. Also, EEG screening may prove to be useful for refractory cases regardless of age, gender, or diagnosis.

Neuromodulation: urodynamic effects of sacral (S3) spinal nerve stimulation in patients with detrusor instability or detrusor hyperflexia.

PubMed

Bosch, J L; Groen, J

1998-05-01

The aim of this study was to determine the urodynamic effects of sacral (S3) nerve stimulation in patients with urge incontinence due to detrusor overactivity which has been refractory to conservative treatment. A total of 24 patients with idiopathic detrusor instability and five with neurogenic hyperreflexia were studied urodynamically before and 6 months after a permanent S3 foramen electrode implant. The urodynamic studies at follow-up were done with the stimulus on. Clinically, the average voiding frequency, the number of leakage episodes and pad use per 24 h decreased significantly. Improvement in several urodynamic parameters was noted. In the idiopathic as well as in the neurogenic group, the correlation between symptomatic and urodynamic improvement was incomplete. Neuromodulation leads to improvement of several urodynamic parameters in patients with urge incontinence due to detrusor overactivity which has been refractory to conservative treatment and appears to be a valuable treatment option in these patients.

Lumbar Spinal Stenosis: Who Should Be Fused? An Updated Review

PubMed Central

Hasankhani, Ebrahim Ghayem; Ashjazadeh, Amir

2014-01-01

Lumbar spinal stenosis (LSS) is mostly caused by osteoarthritis (spondylosis). Clinically, the symptoms of patients with LSS can be categorized into two groups; regional (low back pain, stiffness, and so on) or radicular (spinal stenosis mainly presenting as neurogenic claudication). Both of these symptoms usually improve with appropriate conservative treatment, but in refractory cases, surgical intervention is occasionally indicated. In the patients who primarily complain of radiculopathy with an underlying biomechanically stable spine, a decompression surgery alone using a less invasive technique may be sufficient. Preoperatively, with the presence of indicators such as failed back surgery syndrome (revision surgery), degenerative instability, considerable essential deformity, symptomatic spondylolysis, refractory degenerative disc disease, and adjacent segment disease, lumbar fusion is probably recommended. Intraoperatively, in cases with extensive decompression associated with a wide disc space or insufficient bone stock, fusion is preferred. Instrumentation improves the fusion rate, but it is not necessarily associated with improved recovery rate and better functional outcome. PMID:25187873

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

Cellular STAT3 functions via PCBP2 to restrain Epstein-Barr Virus lytic activation in B lymphocytes.

PubMed

Koganti, Siva; Clark, Carissa; Zhi, Jizu; Li, Xiaofan; Chen, Emily I; Chakrabortty, Sharmistha; Hill, Erik R; Bhaduri-McIntosh, Sumita

2015-05-01

A major hurdle to killing Epstein-Barr virus (EBV)-infected tumor cells using oncolytic therapy is the presence of a substantial fraction of EBV-infected cells that does not support the lytic phase of EBV despite exposure to lytic cycle-promoting agents. To determine the mechanism(s) underlying this refractory state, we developed a strategy to separate lytic from refractory EBV-positive (EBV(+)) cells. By examining the cellular transcriptome in separated cells, we previously discovered that high levels of host STAT3 (signal transducer and activator of transcription 3) curtail the susceptibility of latently infected cells to lytic cycle activation signals. The goals of the present study were 2-fold: (i) to determine the mechanism of STAT3-mediated resistance to lytic activation and (ii) to exploit our findings to enhance susceptibility to lytic activation. We therefore analyzed our microarray data set, cellular proteomes of separated lytic and refractory cells, and a publically available STAT3 chromatin immunoprecipitation sequencing (ChIP-Seq) data set to identify cellular PCBP2 [poly(C)-binding protein 2], an RNA-binding protein, as a transcriptional target of STAT3 in refractory cells. Using Burkitt lymphoma cells and EBV(+) cell lines from patients with hypomorphic STAT3 mutations, we demonstrate that single cells expressing high levels of PCBP2 are refractory to spontaneous and induced EBV lytic activation, STAT3 functions via cellular PCBP2 to regulate lytic susceptibility, and suppression of PCBP2 levels is sufficient to increase the number of EBV lytic cells. We expect that these findings and the genome-wide resources that they provide will accelerate our understanding of a longstanding mystery in EBV biology and guide efforts to improve oncolytic therapy for EBV-associated cancers. Most humans are infected with Epstein-Barr virus (EBV), a cancer-causing virus. While EBV generally persists silently in B lymphocytes, periodic lytic (re)activation of latent virus is central to its life cycle and to most EBV-related diseases. However, a substantial fraction of EBV-infected B cells and tumor cells in a population is refractory to lytic activation. This resistance to lytic activation directly and profoundly impacts viral persistence and the effectiveness of oncolytic therapy for EBV(+) cancers. To identify the mechanisms that underlie susceptibility to EBV lytic activation, we used host gene and protein expression profiling of separated lytic and refractory cells. We find that STAT3, a transcription factor overactive in many cancers, regulates PCBP2, a protein important in RNA biogenesis, to regulate susceptibility to lytic cycle activation signals. These findings advance our understanding of EBV persistence and provide important leads on devising methods to improve viral oncolytic therapies. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Treatment of refractory uveitic macular edema: results of a first and second implant of long-acting intravitreal dexamethasone

PubMed Central

Zola, Marta; Briamonte, Cristina; Lorenzi, Umberto; Machetta, Federica; Grignolo, Federico M; Fea, Antonio M

2017-01-01

Purpose The purpose of this study was to report the functional and anatomical outcomes of a prospective study resulting from repeated dexamethasone intravitreal implants in patients with uveitic refractory macular edema. Methods Twelve eyes of 9 patients with intermediate and posterior noninfectious inflammatory uveitis complicated with refractory macular edema were regularly reviewed after a dexamethasone intravitreal implant. Patients were examined at baseline, 30, 90, 135, and 180 days with best-corrected visual acuity (BCVA), complete slit-lamp examination, intraocular pressure (IOP), optical coherence tomography, and fluorescein angiography. After 6 months of follow-up, eyes were reassessed to receive a second implant. Results BCVA significantly improved when comparing the baseline values after the first and second implant (16.2 and 25.8 letters, respectively, 9.6 letters improvements, p<0.05). BCVA was better after the second implant compared to the first one throughout the follow-up, but without statistical significance. Mean central macular thickness (CMT) was 446.3±129.9 μm at baseline and was significantly reduced until day 135 (p<0.05). CMT reductions after the second injection showed a similar pattern, though differences were not statistically significant. Cataract progression was observed in 4 of 8 phakic eyes (50%) after the first implant, and in 2 of 3 phakic eyes following the second implant, with 1 eye requiring cataract surgery. One eye developed an IOP >30 mmHg 30 days after the second implant, treated topically. Conclusion Repeated dexamethasone intravitreal implants in uveitic patients with refractory macular edema can be used effectively in a clinical setting with an acceptable safety profile. PMID:29184384

Lenalidomide in multiple myeloma: an evidence-based review of its role in therapy

PubMed Central

Richardson, Paul; Mitsiades, Constantine; Laubach, Jacob; Schlossman, Robert; Ghobrial, Irene; Hideshima, Teru; Munshi, Nikhil; Anderson, Kenneth

2010-01-01

Introduction: Multiple myeloma (MM) is a relatively common and incurable hematological malignancy. Currently, there is no single standard therapy, with choice of treatment dependent on individual patient factors. Lenalidomide is an immunomodulatory drug with potent antitumor, antiangiogenic, immunomodulatory, and proapoptotic activity in MM. Aims: To evaluate the evidence for the use of lenalidomide in its current indication in relapsed or refractory MM, and additionally its investigational use for the treatment of newly diagnosed MM. Evidence review: In patients with relapsed and refractory MM, adding lenalidomide to high-dose dexamethasone significantly improves response rates and time-to-progression, relative to high-dose dexamethasone alone. This translates into a significant extension of overall survival (with a median extension of 9.1 months in a pivotal phase III study). Outcome is independent of patient age, number of previous therapies, type of previous therapy (including thalidomide or autologous stem cell transplantation), renal impairment, and β2-microglobulin level. Evidence suggests that combining lenalidomide with low-dose dexamethasone improves outcomes in patients with newly diagnosed disease and is superior to lenalidomide combined with high-dose dexamethasone. Myelosuppression is the predominant toxicity observed, although some studies have shown high incidences of venous thromboembolism in the absence of prophylactic antithrombotic anticoagulation therapy. There is currently only limited evidence regarding the health economics of lenalidomide. Role in therapy: The encouraging results obtained with lenalidomide alone and in combination with dexamethasone in patients with relapsed or refractory MM have led to its adoption as a recommended therapy in patients who have received at least one prior treatment. Emerging evidence supports the ongoing investigation of lenalidomide in combination with low-dose dexamethasone, and in other combinations including bortezomib, for use both in relapsed, refractory, and newly diagnosed MM. PMID:20694078

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

Golimumab in refractory uveitis related to spondyloarthritis. Multicenter study of 15 patients.

PubMed

Calvo-Río, Vanesa; Blanco, Ricardo; Santos-Gómez, Montserrat; Rubio-Romero, Esteban; Cordero-Coma, Miguel; Gallego-Flores, Adela; Veroz, Raúl; Torre, Ignacio; Hernández, Félix Francisco; Atanes, Antonio; Loricera, Javier; González-Vela, M C; Palmou, Natalia; Hernández, José L; González-Gay, Miguel A

2016-08-01

To assess the efficacy of golimumab (GLM) in refractory uveitis associated to spondyloarthritis (SpA). Multicenter study of SpA-related uveitis refractory to at least 1 immunosuppressive drug. The main outcome variables were degree of anterior and posterior chamber inflammation, visual acuity, and macular thickness. A total of 15 patients (13 men/2 women; 18 affected eyes; mean age 39 ± 6 years) were evaluated. The underlying SpA subtypes were ankylosing spondylitis (n = 8), psoriatic arthritis (n = 6) and non-radiographic axial SpA (n = 1). The ocular involvement patterns were recurrent anterior uveitis in 8 patients and chronic anterior uveitis in 7. Before GLM they have received methotrexate (n = 13), sulfasalazine (n = 6), pulses of methylprednisolone (n = 4), azathioprine (n = 3), leflunomide (n = 2), and cyclosporine (n = 1). Overall, 10 of them had also been treated with TNF-α blockers; etanercept (n = 7), adalimumab (n = 7), infliximab (n = 6), and certolizumab (n = 1). GLM was given at the standard dose (50mg/sc/monthly) as monotherapy (n = 7) or in combination with conventional immunosuppressive drugs (n = 8), mainly methotrexate. Most patients had rapid and progressive improvement of intraocular inflammation parameters. The median number of cells in the anterior chamber at 2 years [0 (0-0)] was significantly reduced compared to baseline findings [1 (0-3); p = 0.04]. The mean best corrected visual acuity value also improved (0.84 ± 0.3 at 2 years versus 0.62 ± 0.3 at baseline; p = 0.03). Only minor side effects were observed after a mean follow-up of 23 ± 7 months. Our results indicate that GLM may be a useful therapeutic option in refractory SpA-related uveitis. Copyright © 2016 Elsevier Inc. All rights reserved.

A review of a novel, Bruton's tyrosine kinase inhibitor, ibrutinib.

PubMed

Lee, Chung-Shien; Rattu, Mohammad A; Kim, Sara S

2016-02-01

Ibrutinib, a Bruton's kinase inhibitor, was granted an accelerated approval by the US Food and Drug Administration in November, 2013, for the treatment of relapsed or refractory mantle cell lymphoma and subsequently for the treatment of relapsed refractory chronic lymphocytic leukemia in February, 2014. In the pivotal phase 2 study of 111 patients with relapsed or refractory mantle cell lymphoma, the overall response rate in patients who received ibrutinib 560 mg daily was 68%. The median progression-free survival was 13.9 months, and the overall survival was 58% at 18 months. In a recently published phase 3 trial (RESONATE) that compared ibrutinib and ofatumumab for the treatment of relapsed and refractory chronic lymphocytic leukemia or small lymphocytic lymphoma, ibrutinib at the daily dosage of 420 mg demonstrated a significantly higher overall response rate (43% in ibrutinib vs. 4% in ofatumumab) and a significantly improved overall survival at 12 months (90% ibrutinib vs. 81% ofatumumab). Similar clinical benefits were shown regardless of del (17 p). Ibrutinib was well tolerated, and dose-limiting toxicity was not observed. Ibrutinib has shown durable remission, improved progression-free survival and overall survival, and favorable safety profile in indolent B-cell lymphoid malignancies. Ibrutinib, as a monotherapy, is an effective treatment modality as a salvage therapy for treatment of mantle cell lymphoma and chronic lymphocytic leukemia / small lymphocytic lymphoma, particularly in older patients (age ≥70 years) who are not a candidate for intensive chemotherapy and/or those with del (17 p). In patients with chronic lymphocytic leukemia and del (17 p), the current practice guideline recommends ibrutinib as an upfront treatment option. Current on-going trials will further define its role as upfront therapy and/or as a combination therapy in indolent B-cell lymphoid malignancies. © The Author(s) 2014.

Deep Brain Stimulation of Medial Dorsal and Ventral Anterior Nucleus of the Thalamus in OCD: A Retrospective Case Series

PubMed Central

Lenartz, Doris; Kuhn, Jens; Sturm, Volker

2016-01-01

Background The current notion that cortico-striato-thalamo-cortical circuits are involved in the pathophysiology of obsessive-compulsive disorder (OCD) has instigated the search for the most suitable target for deep brain stimulation (DBS). However, despite extensive research, uncertainty about the ideal target remains with many structures being underexplored. The aim of this report is to address a new target for DBS, the medial dorsal (MD) and the ventral anterior (VA) nucleus of the thalamus, which has thus far received little attention in the treatment of OCD. Methods In this retrospective trial, four patients (three female, one male) aged 31–48 years, suffering from therapy-refractory OCD underwent high-frequency DBS of the MD and VA. In two patients (de novo group) the thalamus was chosen as a primary target for DBS, whereas in two patients (rescue DBS group) lead implantation was performed in a rescue DBS attempt following unsuccessful primary stimulation. Results Continuous thalamic stimulation yielded no significant improvement in OCD symptom severity. Over the course of thalamic DBS symptoms improved in only one patient who showed “partial response” on the Yale-Brown Obsessive Compulsive (Y-BOCS) Scale. Beck Depression Inventory scores dropped by around 46% in the de novo group; anxiety symptoms improved by up to 34%. In the de novo DBS group no effect of DBS on anxiety and mood was observable. Conclusion MD/VA-DBS yielded no adequate alleviation of therapy-refractory OCD, the overall strategy in targeting MD/VA as described in this paper can thus not be recommended in DBS for OCD. The magnocellular portion of MD (MDMC), however, might prove a promising target in the treatment of mood related and anxiety disorders. PMID:27504631

Effect of 13q deletion on IL-6 production in patients with multiple myeloma: a hypothesis may hold true.

PubMed

Neemat, Kassem; Rania, Khalifa; Tarek, Mohamed; Hamdy, Abdel Azim

2014-01-01

Numerous studies have shown a correlation between 13q deletion and poor prognosis in multiple myeloma (MM), but the mechanisms are not fully understood. Earlier studies suggest that this lesion involves large segments or the entire long arm involving the retinoblastoma (Rb) gene. In myeloma, Rb gene is believed to down regulate interleukin-6 (IL-6) which plays a central role in the pathogenesis of MM. Therefore, it has been hypothesized that loss of the Rb gene might be associated with very high expression of IL-6 and subsequent bad prognosis. Hence this study evaluates IL-6 production in MM patients with and without 13q deletions and assesses their response to conventional and new therapeutic regimens. Forty MM patients and 20 matched controls were included in this study. Interphase fluorescence in situ hybridization (FISH) analysis was performed using LSI 13q14-specific probe. Serum levels of IL-6 were determined by ELISA. All patients received conventional chemotherapy. Refractory patients received other therapeutic regimens of Thalidomide or Bortezomib. Significant increase (p < 0.001) of IL-6 production was recorded in patients with a 13q deletion compared to patients with normal chromosome 13q status. These patients were also refractory to conventional chemotherapy but showed striking response to Thalidomide or Bortezomib. This study suggests that 13q deletions are associated with increased production of IL-6 in MM and this could be a possible cause of the associated bad prognosis. In addition, the results also show the potential to improve responses in patients with refractory MM with the introduction of novel therapies.

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.

Phase 1/2 study of immunotherapy with dendritic cells pulsed with autologous tumor lysate in patients with refractory bone and soft tissue sarcoma.

PubMed

Miwa, Shinji; Nishida, Hideji; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Hayashi, Katsuhiro; Yamamoto, Norio; Mizukoshi, Eishiro; Nakamoto, Yasunari; Kaneko, Shuichi; Tsuchiya, Hiroyuki

2017-05-01

There are limited options for the curative treatment of refractory bone and soft tissue sarcomas. The purpose of this phase 1/2 study was to assess the immunological and clinical effects of dendritic cells (DCs) pulsed with autologous tumor lysate (TL) in patients with advanced bone and soft tissue sarcomas. Thirty-seven patients with metastatic or recurrent sarcomas were enrolled in this study. Peripheral blood mononuclear cells obtained from the patients were suspended in media containing interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor. Subsequently, these cells were treated with TL, tumor necrosis factor α, and OK-432. The DCs were injected into the inguinal or axillary region. One treatment course comprised 6 weekly DC injections. The toxicity, clinical response (tumor volume, serum interferon-γ [IFN-γ], and serum IL-12), and oncological outcomes were observed. In total, 47 courses of DC therapy were performed in 37 patients. No severe adverse events or deaths associated with the DC injections were observed in the study patients. Increased serum IFN-γ and IL-12 levels were observed 1 month after the DC injection. Among the 37 patients, 35 patients were assessed for clinical responses: 28 patients showed tumor progression, 6 patients had stable disease, and 1 patient showed a partial response 8 weeks after the DC injection. The 3-year overall and progression-free survival rates of the patients were 42.3% and 2.9%, respectively. Although DC therapy appears safe and resulted in an immunological response in patients with refractory sarcoma, it resulted in an improvement of the clinical outcome in only a small number of patients. Cancer 2017;123:1576-1584. © 2017 American Cancer Society. © 2017 American Cancer Society.

Fragments of e-Cadherin as Biomarkers of Non-erosive Reflux Disease.

PubMed

Jovov, Biljana; Reed, Craig C; Shaheen, Nicholas J; Pruitt, Amy; Ferrell, Kathleen; Orlando, Geraldine S; Djukic, Zorka; Orlando, Roy C

2018-03-01

Approximately, 20% of patients with heartburn and normal endoscopic findings do not symptomatically improve on proton pump inhibitor (PPI) therapy making diagnosis and treatment uncertain. A biomarker distinguishing PPI-responsive from PPI-refractory heartburn is desirable. We performed a pilot study assessing whether carboxy(C)-terminal fragments (CTFs) of e-cadherin in esophageal biopsies or amino(N)-terminal fragments (NTFs) of e-cadherin in serum could serve this purpose. Twenty-nine patients with endoscopy-negative heartburn had esophageal biopsies for CTFs on Western blot and blood for serum NTFs on ELISA. All patients received dexlansoprazole 30 mg daily for 4 weeks, and heartburn was assessed by daily diary entry. Post-treatment blood samples were obtained for serum NTFs. A control group without GERD symptoms (n = 6) had biopsies for CTFs and a second control group (n = 20) blood serum for serum NTFs. Twenty-seven of 29 patients (93.1%) with endoscopy-negative heartburn, but 0 of 6 controls, were positive for CTFs. All patients and controls had measureable serum NTFs, but mean NTFs were significantly higher in those with PPI-responsive heartburn compared to those with PPI-refractory heartburn and controls. Following treatment, 24 of 29 (82.8) patients had relief of heartburn, which associated with a decline in mean NTFs compared to controls. NTFs in PPI-refractory patients (n = 5) were similar to controls before and after PPI therapy. When heartburn responds to PPI, elevated serum NTFs decline to normal. These data suggest that cleaved products of e-cadherin may serve as biomarkers of NERD. Further data are needed to assess and confirm this concept.

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.

[Methylene blue in the treatment of vasodilatory shock: a Meta-analysis].

PubMed

Zhang, Xiongfeng; Gao, Yun; Pan, Pengfei; Wang, Yi; Li, Wenzhe; Yu, Xiangyou

2017-11-01

To investigate the clinical efficacy of methylene blue in the treatment of refractory hypotension caused by vascular paralysis during the course of vasodilatory shock. The related articles were searched by retrieving the terms using methylene blue, vascular paralysis, hemodynamics, hypotension, vasodilatory shock in CNKI, China Biomedical Literature database, Wanfang database, PubMed, Springer Link, and BIOSIS Previews database. The retrieval time was from January 1994 to June 2017. The randomized clinical trials (RCTs) which using methylene blue as the experimental group, normal saline or catecholamine as the control in the treatment of refractory hypotension caused by vascular paralysis during the course of vasodilatory shock were collected. The primary end points were mean arterial pressure (MAP) immediately or 1 hour after the methylene blue administration, and the mortality at the longest follow-up available; the secondary end point was serum lactic acid (Lac) 1 hour after the methylene blue administration. Literature screening, data extraction and quality evaluation were carried out by two researchers. Meta analysis was performed using RevMan 5.3 software. The sensitivity analysis was performed in two trials with low risk of bias. The funnel plot for MAP was performed in five relative trials to analyze the research and publication bias. Totally 269 relative articles were collected, according to the inclusion and exclusion criteria, finally 6 RCTs with 214 patients were enrolled, 108 in methylene blue group, and 106 in control group. Four of the studies were considered to have mild to moderate risk of bias, two studies of high risk of bias. The Meta-analysis demonstrated that compared with the control group, methylene blue could significantly improve MAP [mean difference (MD) = 4.87, 95% confidence interval (95%CI) = 2.61 to 7.13, P < 0.000 1], reduce the serum Lac levels (MD = -1.06, 95%CI = -1.98 to -0.14, P = 0.02), and the mortality was decreased without statistical difference [odds ratio (OR) = 0.58, 95%CI = 0.25 to 1.31, P = 0.19]. Sensitivity analysis was performed in two trials with low risk of bias, which demonstrated methylene blue could exactly increase MAP (MD = 8.93, 95%CI = 1.55 to 16.32, P = 0.02). Funnel plot for MAP was performed in five relative trials which found no obvious publication bias. Methylene blue could significantly increase MAP in the patients with refractory hypotension caused by vascular paralysis during the course of vasodilatory shock, decrease the Lac levels, and does not increase the risk of death. Therefore, methylene blue should be a potential and safe vasoconstrictor.

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

CREATION OF A MODEL TO PREDICT SURVIVAL IN PATIENTS WITH REFRACTORY COELIAC DISEASE USING A MULTINATIONAL REGISTRY

PubMed Central

Rubio-Tapia, Alberto; Malamut, Georgia; Verbeek, Wieke H.M.; van Wanrooij, Roy L.J.; Leffler, Daniel A.; Niveloni, Sonia I.; Arguelles-Grande, Carolina; Lahr, Brian D.; Zinsmeister, Alan R.; Murray, Joseph A.; Kelly, Ciaran P.; Bai, Julio C.; Green, Peter H.; Daum, Severin; Mulder, Chris J.J.; Cellier, Christophe

2016-01-01

Background Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome. Aim To create a prognostic model to estimate survival of patients with refractory coeliac disease. Methods We evaluated predictors of 5-year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap re-sampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5-year mortality. Results The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across 7 centers (range of 11–63 cases per center). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during 5-year follow-up (cumulative 5-year all-cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5-year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval: 1.38, 3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% confidence interval: 1.22, 6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% confidence interval: 0.61, 0.85). A simple weighted 3-factor risk score was created to estimate 5-year survival. Conclusions Using data from a multinational registry and previously-reported risk factors, we create a prognostic model to predict 5-year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow-up. PMID:27485029

Cost-utility analysis of intravenous immunoglobulin for the treatment of steroid-refractory dermatomyositis in Thailand.

PubMed

Bamrungsawad, Naruemon; Chaiyakunapruk, Nathorn; Upakdee, Nilawan; Pratoomsoot, Chayanin; Sruamsiri, Rosarin; Dilokthornsakul, Piyameth

2015-05-01

Intravenous immunoglobulin (IVIG) has been shown to be effective in treating steroid-refractory dermatomyositis (DM). There remains no evidence of its cost-effectiveness in Thailand. Our objective was to estimate the cost utility of IVIG as a second-line therapy in steroid-refractory DM in Thailand. A Markov model was developed to estimate the relevant costs and health benefits for IVIG plus corticosteroids in comparison with immunosuppressant plus corticosteroids in steroid-refractory DM from a societal perspective over a patient's lifetime. The effectiveness and utility parameters were obtained from clinical literature, meta-analyses, medical record reviews, and patient interviews, whereas cost data were obtained from an electronic hospital database and patient interviews. Costs are presented in $US, year 2012 values. All future costs and outcomes were discounted at a rate of 3% per annum. One-way and probabilistic sensitivity analyses were also performed. Over a lifetime horizon, the model estimated treatment under IVIG plus corticosteroids to be cost saving compared with immunosuppressant plus corticosteroids, where the saving of costs and incremental quality-adjusted life-years (QALYs) were $US4738.92 and 1.96 QALYs, respectively. Sensitivity analyses revealed that probability of response of immunosuppressant plus corticosteroids was the most influential parameter on incremental QALYs and costs. At a societal willingness-to-pay threshold in Thailand of $US5148 per QALY gained, the probability of IVIG being cost effective was 97.6%. The use of IVIG plus corticosteroids is cost saving compared with treatment with immunosuppressant plus corticosteroids in Thai patients with steroid-refractory DM. Policy makers should consider using our findings in their decision-making process for adding IVIG to corticosteroids as the second-line therapy for steroid-refractory DM patients.

Creation of a model to predict survival in patients with refractory coeliac disease using a multinational registry.

PubMed

Rubio-Tapia, A; Malamut, G; Verbeek, W H M; van Wanrooij, R L J; Leffler, D A; Niveloni, S I; Arguelles-Grande, C; Lahr, B D; Zinsmeister, A R; Murray, J A; Kelly, C P; Bai, J C; Green, P H; Daum, S; Mulder, C J J; Cellier, C

2016-10-01

Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome. To create a prognostic model to estimate survival of patients with refractory coeliac disease. We evaluated predictors of 5-year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap resampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5-year mortality. The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across seven centres (range of 11-63 cases per centre). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during a 5-year follow-up (cumulative 5-year all-cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5-year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval, CI: 1.38-3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% CI: 1.22-6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% CI: 0.61-0.85). A simple weighted three-factor risk score was created to estimate 5-year survival. Using data from a multinational registry and previously reported risk factors, we create a prognostic model to predict 5-year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow-up. © 2016 John Wiley & Sons Ltd.

Lexical Access and Dual-Task Performance: Determining the Locus of the Bottleneck

NASA Technical Reports Server (NTRS)

Allen, Phil

2004-01-01

During the two years of funding for NASA Grant "NCC21325, Lexical access and dual-task performance: Determining the locus of the bottleneck," we completed three experiments involving the psychological refractory period (PRP) and word frequency.

Safety and Patient Acceptability of Stellate Ganglion Blockade as a Treatment Adjunct for Combat-Related Post-Traumatic Stress Disorder: A Quality Assurance Initiative.

PubMed

McLean, Brian

2015-09-10

 To perform a quality assurance and performance improvement project through review of our single center data on the safety and patient acceptability of the stellate ganglion blockade (SGB) procedure for the relief of symptoms related to chronic post-traumatic stress disorder.  Our interventional pain management service has been offering trials of SGB therapy to assist with the management of the sympathetically mediated anxiety and hyperarousal symptoms of severe and treatment-refractory combat-related PTSD. There have been multiple case series in the literature describing the potential impact of this procedure for PTSD symptom management as well as the safety of image-guided procedures. We wished to ensure that we were performing this procedure safely and that patients were tolerating and accepting of this adjunctive treatment option.  We conducted a review of our quality assurance and performance improvement data over the past 18 months during which we performed 250 stellate ganglion blocks for the management of PTSD symptoms to detect any potential complications or unanticipated side effects.  We also analyzed responses from an anonymous patient de-identified survey collected regarding the comfort and satisfaction associated with the procedure.  We did not identify any immediate post-procedural complications or delayed complications from any of the 250 procedures performed from November 2013 to April 2015. Of the 110 surveys that were returned and tabulated, 100% of the patients surveyed were overall satisfied with our process and with the procedure, 100% said they would recommend the procedure to a friend, and 95% stated that they would be willing to undergo as many repeat procedures as necessary based on little discomfort and tolerable side effects.  Our quality assurance assessment suggests that in our center the SGB procedure for PTSD is a safe, well-tolerated, and acceptable treatment adjunct in the management of severe symptoms associated with chronic treatment-refractory PTSD. Patient satisfaction responses are strongly suggestive of high therapeutic value, and further studies are indicated to determine the effectiveness, duration of action, and optimal treatment regimen.

Unusual spiral wave dynamics in the Kessler-Levine model of an excitable medium.

PubMed

Oikawa, N; Bodenschatz, E; Zykov, V S

2015-05-01

The Kessler-Levine model is a two-component reaction-diffusion system that describes spatiotemporal dynamics of the messenger molecules in a cell-to-cell signaling process during the aggregation of social amoeba cells. An excitation wave arising in the model has a phase wave at the wave back, which simply follows the wave front after a fixed time interval with the same propagation velocity. Generally speaking, the medium excitability and the refractoriness are two important factors which determine the spiral wave dynamics in any excitable media. The model allows us to separate these two factors relatively easily since the medium refractoriness can be changed independently of the medium excitability. For rigidly rotating waves, the universal relationship has been established by using a modified free-boundary approach, which assumes that the front and the back of a propagating wave are thin in comparison to the wave plateau. By taking a finite thickness of the domain boundary into consideration, the validity of the proposed excitability measure has been essentially improved. A novel method of numerical simulation to suppress the spiral wave instabilities is introduced. The trajectories of the spiral tip observed for a long refractory period have been investigated under a systematic variation of the medium refractoriness.

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

The use of high-dose insulin therapy and intravenous lipid emulsion to treat severe, refractory diltiazem toxicosis in a dog.

PubMed

Maton, Barbara L; Simmonds, Erin E; Lee, Justine A; Alwood, Amy J

2013-01-01

To describe the novel use of high-dose insulin (HDI) therapy and intravenous lipid emulsion (ILE) to treat refractory, severe diltiazem toxicosis in a dog. A 4-year-old Pomeranian was presented for treatment 2.5 hours following ingestion of a diltiazem extended-release capsule. Toxic ingestion was calculated at a maximum exposure of 79 mg/kg, with a reported canine LD50 of 50 mg/kg. Clinical signs of progressive hypotension and severe bradycardia with atrial standstill were observed, which persisted despite treatment with atropine, calcium, glucagon, and dopamine. The novel use of HDI and ILE as part of therapy for diltiazem toxicosis resulted in clinical resolution of life-threatening signs. Within 1 hour of initiating HDI therapy, the clinical signs improved, and with continued treatment, the patient remained normotensive and survived to discharge. To the authors' knowledge, this is the first reported clinical case describing the use of both HDI and ILE therapy in the treatment of severe refractory diltiazem toxicosis in veterinary medicine. No significant adverse effects were observed from the treatment. In veterinary patients with severe refractory calcium channel blocker toxicosis, the use of HDI and ILE should be considered for life-threatening clinical signs. © Veterinary Emergency and Critical Care Society 2013.

Comparison of two doses of intravenous temsirolimus in patients with relapsed/refractory mantle cell lymphoma.

PubMed

Jurczak, Wojciech; Ramanathan, Sundra; Giri, Pratyush; Romano, Alessandra; Mocikova, Heidi; Clancy, Jill; Lechuga, Mariajose; Casey, Michelle; Boni, Joseph; Giza, Agnieszka; Hess, Georg

2018-03-01

Temsirolimus 175 mg once-weekly for 3 weeks, followed by 75 mg once-weekly intravenously dosed (175/75 mg) is approved in the European Union for treatment of relapsed/refractory mantle cell lymphoma (MCL). A phase IV study explored whether similar efficacy, but improved safety could be achieved with 75 mg without 175 mg loading doses (ClinicaTrials.gov: NCT01180049). Patients with relapsed/refractory MCL were randomized to once-weekly temsirolimus 175/75 mg (n = 47) or 75 mg (n = 42). Treatment continued until objective disease progression. Primary endpoint: progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events (AEs). Median PFS was 4.3 versus 4.5 months (hazard ratio [HR] 0.731; 80% confidence interval [CI], 0.520-1.027), and median OS 18.7 versus 11.0 months (HR 0.681; 80% CI, 0.472-0.982) with 175/75 mg versus 75 mg. There were fewer patients with serious AEs, dose reduction, or death with 175/75 mg (57.4%, 48.9%, and 48.9%) versus 75 mg (73.8%, 64.3%, and 65.1%). Temsirolimus 175/75 mg remains the preferred dosing regimen for relapsed/refractory MCL.

Unusual spiral wave dynamics in the Kessler-Levine model of an excitable medium

NASA Astrophysics Data System (ADS)

Oikawa, N.; Bodenschatz, E.; Zykov, V. S.

2015-05-01

The Kessler-Levine model is a two-component reaction-diffusion system that describes spatiotemporal dynamics of the messenger molecules in a cell-to-cell signaling process during the aggregation of social amoeba cells. An excitation wave arising in the model has a phase wave at the wave back, which simply follows the wave front after a fixed time interval with the same propagation velocity. Generally speaking, the medium excitability and the refractoriness are two important factors which determine the spiral wave dynamics in any excitable media. The model allows us to separate these two factors relatively easily since the medium refractoriness can be changed independently of the medium excitability. For rigidly rotating waves, the universal relationship has been established by using a modified free-boundary approach, which assumes that the front and the back of a propagating wave are thin in comparison to the wave plateau. By taking a finite thickness of the domain boundary into consideration, the validity of the proposed excitability measure has been essentially improved. A novel method of numerical simulation to suppress the spiral wave instabilities is introduced. The trajectories of the spiral tip observed for a long refractory period have been investigated under a systematic variation of the medium refractoriness.

Vagus Nerve Stimulation in Intractable Childhood Epilepsy: a Korean Multicenter Experience

PubMed Central

You, Su Jeong; Kang, Hoon-Chul; Kim, Heung Dong; Kim, Deok-Soo; Hwang, Yong Soon; Kim, Dong Suk; Lee, Jung-Kyo; Park, Sang Keun

2007-01-01

We evaluated the long-term outcome of vagus nerve stimulation (VNS) in 28 children with refractory epilepsy. Of these 28 children, 15 (53.6%) showed a >50% reduction in seizure frequency and 9 (32.1%) had a >75% reduction. When we compared seizure reduction rates according to seizure types (generalized vs. partial) and etiologies (symptomatic vs. cryptogenic), we found no significant differences. In addition, there was no correlation between the length of the stimulation period and treatment effect. The seizure reduction rate, however, tended to be inversely related to the seizure duration before VNS implantation and age at the time of VNS therapy. VNS also improved quality of life in this group of patients, including improved memory in 9 (32.1%), improved mood in 12 (42.9%), improved behavior in 11 (39.3%), improved altertness in 12 (42.9%), improved achievement in 6 (21.4%), and improved verbal skills in 8 (28.6%). Adverse events included hoarseness in 7 patients, dyspnea at sleep in 2 patients, and wound infection in 1 patient, but all were transient and successfully managed by careful follow-up and adjustment of parameters. These results indicate that VNS is a safe and effective alternative therapy for pediatric refractory epilepsy, without significant adverse events. PMID:17596651

Vorinostat and hydroxychloroquine improve immunity and inhibit autophagy in metastatic colorectal cancer.

PubMed

Patel, Sukeshi; Hurez, Vincent; Nawrocki, Steffan T; Goros, Martin; Michalek, Joel; Sarantopoulos, John; Curiel, Tyler; Mahalingam, Devalingam

2016-09-13

Hydroxychloroquine (HCQ) enhances the anti-cancer activity of the histone deacetylase inhibitor, vorinostat (VOR), in pre-clinical models and early phase clinical studies of metastatic colorectal cancer (mCRC). Mechanisms could include autophagy inhibition, accumulation of ubiquitinated proteins, and subsequent tumor cell apoptosis. There is growing evidence that autophagy inhibition could lead to improved anti-cancer immunity. To date, effects of autophagy on immunity have not been reported in cancer patients. To address this, we expanded an ongoing clinical study to include patients with advanced, refractory mCRC to evaluate further the clinical efficacy and immune effects of VOR plus HCQ. Refractory mCRC patients received VOR 400 milligrams orally with HCQ 600 milligrams orally daily, in a 3-week cycle. The primary endpoint was median progression-free survival (mPFS). Secondary endpoints include median overall survival (mOS), adverse events (AE), pharmacodynamic of inhibition of autophagy in primary tumors, immune cell analyses, and cytokine levels. Twenty patients were enrolled (19 evaluable for survival) with a mPFS of 2.8 months and mOS of 6.7 months. Treatment-related grade 3-4 AEs occurred in 8 patients (40%), with fatigue, nausea/vomiting, and anemia being the most common. Treatment significantly reduced CD4+CD25hiFoxp3+ regulatory and PD-1+ (exhausted) CD4+ and CD8+ T cells and decreased CD45RO-CD62L+ (naive) T cells, consistent with improved anti-tumor immunity. On-study tumor biopsies showed increases in lysosomal protease cathepsin D and p62 accumulation, consistent with autophagy inhibition. Taken together, VOR plus HCQ is active, safe and well tolerated in refractory CRC patients, resulting in potentially improved anti-tumor immunity and inhibition of autophagy.

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.

Improved Rare-Earth Emitter Hollow Cathode

NASA Technical Reports Server (NTRS)

Goebel, Dan M.

2011-01-01

An improvement has been made to the design of the hollow cathode geometry that was created for the rare-earth electron emitter described in Compact Rare Earth Emitter Hollow Cathode (NPO-44923), NASA Tech Briefs, Vol. 34, No. 3 (March 2010), p. 52. The original interior assembly was made entirely of graphite in order to be compatible with the LaB6 material, which cannot be touched by metals during operation due to boron diffusion causing embrittlement issues in high-temperature refractory materials. Also, the graphite tube was difficult to machine and was subject to vibration-induced fracturing. This innovation replaces the graphite tube with one made out of refractory metal that is relatively easy to manufacture. The cathode support tube is made of molybdenum or molybdenum-rhenium. This material is easily gun-bored to near the tolerances required, and finish machined with steps at each end that capture the orifice plate and the mounting flange. This provides the manufacturability and robustness needed for flight applications, and eliminates the need for expensive e-beam welding used in prior cathodes. The LaB6 insert is protected from direct contact with the refractory metal tube by thin, graphite sleeves in a cup-arrangement around the ends of the insert. The sleeves, insert, and orifice plate are held in place by a ceramic spacer and tungsten spring inserted inside the tube. To heat the cathode, an insulating tube is slipped around the refractory metal hollow tube, which can be made of high-temperature materials like boron nitride or aluminum nitride. A screw-shaped slot, or series of slots, is machined in the outside of the ceramic tube to constrain a refractory metal wire wound inside the slot that is used as the heater. The screw slot can hold a single heater wire that is then connected to the front of the cathode tube by tack-welding to complete the electrical circuit, or it can be a double slot that takes a bifilar wound heater with both leads coming out the back. This configuration replaces the previous sheathed heater design that limited the cycling-life of the cathode.

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

Biodegradable stents for the treatment of refractory or recurrent benign esophageal stenosis.

PubMed

Imaz-Iglesia, Iñaki; García-Pérez, Sonia; Nachtnebel, Anna; Martín-Águeda, Belén; Sánchez-Piedra, Carlos; Karadayi, Bilgehan; Demirbaş, Ali Rıza

2016-06-01

Esophageal stents are used for the treatment of refractory and recurrent dyphagias. In 2007, esophageal biodegradable stents (EBS) were authorised as an alternative to existing metal and plastic stents in Europe. The advantages claimed for EBS are fewer complications concerning tissue ingrowth, stent migration and stent removal. We performed a systematic review to evaluate the efficacy and safety of EBS compared to fully-covered self-expanding metal stents, self-expanding plastic stents, and esophageal dilation for the treatment of refractory or recurrent benign esophageal stenosis. Three comparative studies (one randomized controlled trial and two cohort studies) were assessed. The studies used different inclusion criteria, had a very small (sample) size and the quality of the evidence was very low. Expert commentary: The current evidence is insufficient to determine the relative efficacy or safety of esophageal biodegradable stents. The results of this systematic review should be updated once new evidence is available.

Statistical analysis of the pulse-coupled synchronization strategy for wireless sensor networks

PubMed Central

Wang, Yongqiang; Núñez, Felipe; Doyle, Francis J.

2013-01-01

Pulse-coupled synchronization is attracting increased attention in the sensor network community. Yet its properties have not been fully investigated. Using statistical analysis, we prove analytically that by controlling the number of connections at each node, synchronization can be guaranteed for generally pulse-coupled oscillators even in the presence of a refractory period. The approach does not require the initial phases to reside in half an oscillation cycle, which improves existing results. We also find that a refractory period can be strategically included to reduce idle listening at nearly no sacrifice to the synchronization probability. Given that reduced idle listening leads to higher energy efficiency in the synchronization process, the strategically added refractory period makes the synchronization scheme appealing to cheap sensor nodes, where energy is a precious system resource. We also analyzed the pulse-coupled synchronization in the presence of unreliable communication links and obtained similar results. QualNet experimental results are given to confirm the effectiveness of the theoretical predictions. PMID:24324322

Chimeric antigen receptor (CAR)-directed adoptive immunotherapy: a new era in targeted cancer therapy.

PubMed

Chen, Yamei; Liu, Delong

2014-01-01

As a result of the recent advances in molecular immunology, virology, genetics, and cell processing, chimeric antigen receptor (CAR)-directed cancer therapy has finally arrived for clinical application. CAR-directed adoptive immunotherapy represents a novel form of gene therapy, cellular therapy, and immunotherapy, a combination of three in one. Early phase clinical trial was reported in patients with refractory chronic lymphoid leukemia with 17p deletion. Accompanying the cytokine storm and tumor lysis syndrome was the shocking disappearance of the leukemia cells refractory to chemotherapy and monoclonal antibodies. CAR therapy was reproduced in both children and adults with refractory acute lymphoid leukemia. The CAR technology is being explored for solid tumor therapy, such as glioma. Close to 30 clinical trials are underway in the related fields (www.clinicaltrials.gov). Further improvement in gene targeting, cell expansion, delivery constructs (such as using Sleeping Beauty or Piggyback transposons) will undoubtedly enhance clinical utility. It is foreseeable that CAR-engineered T cell therapy will bring targeted cancer therapy into a new era.

Botulinum toxin A for the Treatment of Overactive Bladder.

PubMed

Hsieh, Po-Fan; Chiu, Hung-Chieh; Chen, Kuan-Chieh; Chang, Chao-Hsiang; Chou, Eric Chieh-Lung

2016-02-29

The standard treatment for overactive bladder starts with patient education and behavior therapies, followed by antimuscarinic agents. For patients with urgency urinary incontinence refractory to antimuscarinic therapy, currently both American Urological Association (AUA) and European Association of Urology (EAU) guidelines suggested that intravesical injection of botulinum toxin A should be offered. The mechanism of botulinum toxin A includes inhibition of vesicular release of neurotransmitters and the axonal expression of capsaicin and purinergic receptors in the suburothelium, as well as attenuation of central sensitization. Multiple randomized, placebo-controlled trials demonstrated that botulinum toxin A to be an effective treatment for patients with refractory idiopathic or neurogenic detrusor overactivity. The urinary incontinence episodes, maximum cystometric capacity, and maximum detrusor pressure were improved greater by botulinum toxin A compared to placebo. The adverse effects of botulinum toxin A, such as urinary retention and urinary tract infection, were primarily localized to the lower urinary tract. Therefore, botulinum toxin A offers an effective treatment option for patients with refractory overactive bladder.

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.

Lightweight alumina refractory aggregate. Final report

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

Swansiger, T.G.; Pearson, A.

1996-07-16

Objective was to develop a lightweight, high alumina refractory aggregate for use in various high performance insulating (low thermal conductivity) refractory applications (e.g., in the aluminium, glass, cement, and iron and steel industries). A new aggregate process was developed through bench and pilot-scale experiments involving extrusion of a blend of calcined and activated alumina powders and organic extrusion aids and binders. The aggregate, with a bulk density approaching 2.5 g/cc, exhibited reduced thermal conductivity and adequate fired strength compared to dense tabular aggregate. Refractory manufacturers were moderately enthusiastic over the results. Alcoa prepared an economic analysis for producing lightweight aggregate,more » based on a retrofit of this process into existing Alcoa production facilities. However, a new, competing lightweight aggregate material was developed by another company; this material (Plasmal{trademark})had a significantly more favorable cost base than the Alcoa/DOE material, due to cheap raw materials and fewer processing steps. In late 1995, Alcoa became a distributor of Plasmal. Alcoa estimated that {ge}75% of the market originally envisioned for the Alcoa/DOE aggregate would be taken by Plasmal. Hence, it was decided to terminate the contract without the full- scale demonstration.« less

Corrosion assessment of refractory materials for high temperature waste vitrification

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

Marra, J.C.; Congdon, J.W.; Kielpinski, A.L.

1995-11-01

A variety of vitrification technologies are being evaluated to immobilize radioactive and hazardous wastes following years of nuclear materials production throughout the Department of Energy (DOE) complex. The compositions and physical forms of these wastes are diverse ranging from inorganic sludges to organic liquids to heterogeneous debris. Melt and off-gas products can be very corrosive at the high temperatures required to melt many of these waste streams. Ensuring material durability is required to develop viable treatment processes. Corrosion testing of materials in some of the anticipated severe environments is an important aspect of the materials identification and selection process. Corrosionmore » coupon tests on typical materials used in Joule heated melters were completed using glass compositions with high salt contents. The presence of chloride in the melts caused the most severe attack. In the metal alloys, oxidation was the predominant corrosion mechanism, while in the tested refractory material enhanced dissolution of the refractory into the glass was observed. Corrosion testing of numerous different refractory materials was performed in a plasma vitrification system using a surrogate heterogeneous debris waste. Extensive corrosion was observed in all tested materials.« less

Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study.

PubMed

Friesecke, Sigrun; Stecher, Stephanie-Susanne; Gross, Stefan; Felix, Stephan B; Nierhaus, Axel

2017-09-01

Sepsis is the most common cause of death in medical intensive care units (ICU). If sepsis progresses to refractory septic shock, mortality may reach 90-100% despite optimum current therapy. Extracorporeal cytokine adsorption in addition to regular therapy was studied prospectively in refractory septic shock patients on a medical ICU. Refractory shock was defined as increasing vasopressor dose required to maintain mean arterial blood pressure above 65 mmHg or increasing lactate levels despite protocol-guided shock therapy for 6 h. We analysed noradrenaline requirements after 6 and 12 h (primary endpoint), lactate clearance after 6 and 12 h, SOFA-scores in the first days and achievement of shock reversal (i.e., normalization of lactate concentrations and sustained discontinuation of vasopressors; secondary endpoints). Twenty consecutive patients with refractory septic shock were included; CytoSorb ® treatment was started after 7.8 ± 3.7 h of shock therapy. Following the initiation of adsorption therapy, noradrenaline dose could be significantly reduced after 6 (-0.4 µg/kg/min; p = 0.03) and 12 h (-0.6 µg/kg/min; p = 0.001). Lactate clearance improved significantly. SOFA-scores on day 0, 1 and 2 remained unchanged. Shock reversal was achieved in 13 (65%) patients; 28-day survival was 45%. In severe septic shock unresponsive to standard treatment, haemodynamic stabilization was achieved using cytokine adsorption therapy, resulting in shock reversal in two-thirds of these patients. The study was registered in the German Register for Clinical Trials (DRKS) No. 00005149.

Radiological Insertion of Denver Peritoneovenous Shunts for Malignant Refractory Ascites: A Retrospective Multicenter Study (JIVROSG-0809)

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

Sugawara, Shunsuke, E-mail: suga_shun@hotmail.com; Sone, Miyuki; Arai, Yasuaki

Purpose: Peritoneal venous shunts (PVSs) are widely used for palliating symptoms of refractory malignant ascites and are recognized as one of the practical methods. However, reliable clinical data are insufficient because most previous reports have been small studies from single centers. We conducted a retrospective, multicenter study to evaluate the safety and efficacy of radiologically placed PVSs in patients with malignant refractory ascites. Methods: A total of 133 patients with malignant ascites refractory to medical therapies were evaluated for patient characteristics, technical success, efficacy, survival times, adverse events, and changes in laboratory data. Results: PVSs were successfully placed in allmore » patients and were effective (i.e., improvement of ascites symptoms lasting 7 days or more) in 110 (82.7%). The median duration of symptom palliation was 26 days and median survival time was 41 days. The most frequent adverse event was PVS dysfunction, which occurred in 60 (45.1%) patients, among whom function was recovered with an additional minimally invasive procedure in 9. Abnormalities in coagulation (subclinical disseminated intravascular coagulation) occurred in 37 (27.8%) patients, although only 7 (5.3%) developed clinical disseminated intravascular coagulation. Other major adverse events were gastrointestinal bleeding (9.8%), sepsis (3.8%), and acute heart failure (3.0%). PVS was least effective in patients with elevated serum creatinine, bloody ascites, or gynecologic tumor. Conclusions: Radiological PVS is a technically feasible and effective method for palliating the symptoms from refractory malignant ascites, but preoperative evaluation and monitoring the postprocedural complications are mandatory to preclude severe adverse events after PVS.« less

Efficacy of infliximab rescue therapy in patients with chronic refractory pouchitis: a multicenter study.

PubMed

Barreiro-de Acosta, M; García-Bosch, O; Souto, R; Mañosa, M; Miranda, J; García-Sanchez, V; Gordillo, J; Chacon, S; Loras, C; Carpio, D; Maroto, N; Menchén, L; Rojas-Feria, M; Sierra, M; Villoria, A; Marin-Jimenez, I

2012-05-01

Despite medical therapy, 30% of patients with ulcerative colitis (UC) need to undergo surgery. Around 50% of patients with proctocolectomy with ileal pouch-anal anastomosis (IPAA) develop complications of the pouch. Clinical evidence for the use of infliximab (IFX) in refractory pouchitis is limited. The aim of this study was to report efficacy of IFX in these patients. A retrospective, multicenter study was designed. Patients older than 18 years with chronic refractory pouchitis treated with IFX (5 mg/kg) were included. Short-term IFX efficacy was evaluated at week 8 and mid-term efficacy at weeks 26 and 52. Complete response was defined as cessation of diarrhea and urgency and partial response as marked clinical improvement but persisting symptoms. The modified Pouchitis Disease Activity Index (mPDAI) without endoscopy was calculated when available. Thirty-three consecutive UC patients with chronic refractory pouchitis were included (18 male, mean age 45 years, range 21-67). At week 8, 21% patients achieved complete response and 63% showed partial clinical response. At weeks 26 and 52, 33% and 27% achieved complete response and 33% and 18% showed partial clinical response, respectively. Thirteen patients (39%) withdrew treatment (four for lack of efficacy, four for loss of response and five for adverse events). None of the potential factors analyzed had an influence on response to IFX. IFX was effective in the short- and mid-term in patients with chronic refractory pouchitis. However, medication had to be discontinued in a high number of patients. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Short-term results of the efficacy of percutaneous tibial nerve stimulation on urinary symptoms and its financial cost

PubMed Central

Kurdoğlu, Zehra; Carr, Danielle; Harmouche, Jihad; Ünlü, Serdar; Kılıç, Gökhan S.

2018-01-01

Objective: Overactive bladder (OAB) affects 16.9% of women in the United States. Percutaneous tibial nerve stimulation (PTNS) is a third-line treatment for patients who are refractory to behavioral and pharmacologic therapies. We aimed to evaluate the effects of PTNS on urinary symptoms in patients diagnosed as having refractory OAB and investigate the cost of medications and clinical visits before and after PTNS treatment. Material and Methods: We reviewed 60 women with refractory OAB treated with PTNS. Episodes of urinary frequency, leakage, urgency, and nocturia; number of follow-up visits; and medications were recorded. The mean quarterly drug, physician, nurse, and provider costs were calculated. The episodes of urinary symptoms, numbers of follow-up visits, and costs of medications and visits before and after PTNS were compared. Results: Of the 60 patients with refractory OAB, 24 patients who completed 12 weekly sessions of initial PTNS were evaluated. The number of urinary symptoms and follow-up visits significantly decreased after PTNS (p<0.05). The average quarterly medication cost decreased from $656.36±292.45 to $375.51±331.79 after PTNS (p=0.001). After PTNS, quarterly physician and nurse visit costs decreased from $81.73±70.39 to $25.89±54.40 and from $55.23±38.32 to $15.53±19.58, respectively (p<0.05). The quarterly total provider cost was similar before and after PTNS. Conclusion: PTNS treatment significantly improved urinary symptoms of patients with refractory OAB and reduced the costs of medications and physician and nurse visits. PMID:29503256

Short-term results of the efficacy of percutaneous tibial nerve stimulation on urinary symptoms and its financial cost.

PubMed

Kurdoğlu, Zehra; Carr, Danielle; Harmouche, Jihad; Ünlü, Serdar; Kılıç, Gökhan S

2018-03-01

Overactive bladder (OAB) affects 16.9% of women in the United States. Percutaneous tibial nerve stimulation (PTNS) is a third-line treatment for patients who are refractory to behavioral and pharmacologic therapies. We aimed to evaluate the effects of PTNS on urinary symptoms in patients diagnosed as having refractory OAB and investigate the cost of medications and clinical visits before and after PTNS treatment. We reviewed 60 women with refractory OAB treated with PTNS. Episodes of urinary frequency, leakage, urgency, and nocturia; number of follow-up visits; and medications were recorded. The mean quarterly drug, physician, nurse, and provider costs were calculated. The episodes of urinary symptoms, numbers of follow-up visits, and costs of medications and visits before and after PTNS were compared. Of the 60 patients with refractory OAB, 24 patients who completed 12 weekly sessions of initial PTNS were evaluated. The number of urinary symptoms and follow-up visits significantly decreased after PTNS (p<0.05). The average quarterly medication cost decreased from $656.36±292.45 to $375.51±331.79 after PTNS (p=0.001). After PTNS, quarterly physician and nurse visit costs decreased from $81.73±70.39 to $25.89±54.40 and from $55.23±38.32 to $15.53±19.58, respectively (p<0.05). The quarterly total provider cost was similar before and after PTNS. PTNS treatment significantly improved urinary symptoms of patients with refractory OAB and reduced the costs of medications and physician and nurse visits.

InnovaSEC in Action: Cost-effectiveness of Barostim in the Treatment of Refractory Hypertension in Spain.

PubMed

Soto, Marcelo; Sampietro-Colom, Laura; Sagarra, Joan; Brugada-Terradellas, Josep

2016-06-01

In Spain, 0.3% of patients with hypertension are refractory to conventional treatment. The complications resulting from deficient control of this condition can lead to poor quality of life for the patient and considerable health care costs. Barostim is an implantable device designed to lower blood pressure in these patients. The aim of this study was to analyze the cost-effectiveness of Barostim compared with drug therapy in hypertensive patients refractory to conventional treatment (at least 3 antihypertensive drugs, including 1 diuretic agent). We used a Markov model adapted to the epidemiology of the Spanish population to simulate the natural history of a cohort of patients with refractory hypertension over their lifetime. Data on the effectiveness of the treatments studied were obtained from the literature, and data on costs were taken from hospital administrative databases and official sources. Deterministic and probabilistic sensitivity analyses were conducted. Barostim increased the number of quality-adjusted life years by 0.78 and reduced the number of hypertension-associated clinical events. The incremental cost-effectiveness ratio in a cohort of men reached 68 726 euros per year of quality-adjusted life. One of the main elements that makes this technology costly is the need for battery replacement. The results were robust. Barostim is not a cost-effective strategy for the treatment of refractory hypertension in Spain. The cost-effectiveness ratio could be improved by future reductions in the cost of the battery. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Rescue Therapy for Refractory Vasospasm after Subarachnoid Hemorrhage

PubMed Central

Durrant, Julia C.; Hinson, Holly E.

2014-01-01

Vasospasm and delayed cerebral ischemia remain to be the common causes of increased morbidity and mortality after aneurysmal subarachnoid hemorrhage. The majority of clinical vasospasm responds to hemodynamic augmentation and direct vascular intervention; however, a percentage of patients continue to have symptoms and neurological decline. Despite suboptimal evidence, clinicians have several options in treating refractory vasospasm in aneurysmal subarachnoid hemorrhage (aSAH), including cerebral blood flow enhancement, intra-arterial manipulations, and intra-arterial and intrathecal infusions. This review addresses standard treatments as well as emerging novel therapies aimed at improving cerebral perfusion and ameliorating the neurologic deterioration associated with vasospasm and delayed cerebral ischemia. PMID:25501582

Magnetohydrodynamic generator electrode

DOEpatents

Marchant, David D.; Killpatrick, Don H.; Herman, Harold; Kuczen, Kenneth D.

1979-01-01

An improved electrode for use as a current collector in the channel of a magnetohydrodynamid (MHD) generator utilizes an elongated monolithic cap of dense refractory material compliantly mounted to the MHD channel frame for collecting the current. The cap has a central longitudinal channel which contains a first layer of porous refractory ceramic as a high-temperature current leadout from the cap and a second layer of resilient wire mesh in contact with the first layer as a low-temperature current leadout between the first layer and the frame. Also described is a monolithic ceramic insulator compliantly mounted to the frame parallel to the electrode by a plurality of flexible metal strips.

Treatment with Botulinum Toxin for Refractory Fever Caused by Severe Spasticity: A Case Series.

PubMed

Lester, Jacobo; Alvarez-Resendiz, Gerardo Esteban; Klériga, Enrique; Videgaray, Fernando; Zambito, Gerardo

2018-06-01

Brain and spinal cord injuries may cause very severe spasticity that occasionally may be associated with persistent fever. We present 14 patients with spasticity and persistent fever, treated with botulinum toxin type A. Their spasticity improved and the fever resolved within a period no greater than 48 h. In all cases, infectious and other non-infectious causes were ruled out. When sustained tonic muscular activity is associated with a significant increase in body temperature and is refractory to the usual drugs used for hyperpyrexia, type A botulinum toxin may be an effective treatment option to control both spasticity and fever.

Resolution of electroconvulsive therapy refractory major depressive disorder with unintentional hypoglycemic seizure: a case report.

PubMed

Rosenblat, Joshua D; Devarajan, Sivakumaran

2013-09-01

We report a 74-year-old white woman with type 1 diabetes and major depressive disorder refractory to multiple medications who received 15 electroconvulsive therapy treatments with minimal improvement. After an accidental hypoglycemic seizure, the patient's symptoms completely resolved. In conclusion, the present case reveals an instance where electroconvulsive therapy-induced seizures appeared to be minimally effective, whereas a single accidental hypoglycemia-induced seizure was incredibly effective for the resolutions of depressive symptoms. Although this case presents a single efficacious use of accidental insulin coma therapy, the applicability is limited because of the known risks of insulin coma therapy.

Getting the best outcomes from epilepsy surgery

PubMed Central

Vakharia, Vejay N.; Witt, Juri‐Alexander; Elger, Christian E.; Staba, Richard; Engel, Jerome

2018-01-01

Neurosurgery is an underutilized treatment that can potentially cure drug‐refractory epilepsy. Careful, multidisciplinary presurgical evaluation is vital for selecting patients and to ensure optimal outcomes. Advances in neuroimaging have improved diagnosis and guided surgical intervention. Invasive electroencephalography allows the evaluation of complex patients who would otherwise not be candidates for neurosurgery. We review the current state of the assessment and selection of patients and consider established and novel surgical procedures and associated outcome data. We aim to dispel myths that may inhibit physicians from referring and patients from considering neurosurgical intervention for drug‐refractory focal epilepsies. Ann Neurol 2018;83:676–690 PMID:29534299

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

PubMed

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

2010-10-01

This paper presents a summary of the evidence review group (ERG) report on the clinical effectiveness and cost-effectiveness of rituximab with chemotherapy compared to chemotherapy only for the treatment of relapsed/refractory chronic lymphocytic leukaemia (CLL) based on the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. Evidence was available in the form of one open-label, ongoing, unpublished randomised controlled trial (RCT), REACH (Rituximab in the Study of Relapsed Chronic Lymphocytic Leukemia), conducted by the manufacturer, which compared rituximab with a fludarabine and cyclophosphamide combination (R-FC) to fludarabine and cyclophosphamide (FC) only. REACH was scheduled to run for 8 years; however, the data provided were immature, with a median observation time at the time of data analysis of 2.1 years. REACH provided evidence of prolonged progression free survival with R-FC compared to FC (10 months, investigators' data), but no evidence of an overall survival benefit with R-FC. Patients refractory to fludarabine and with prior rituximab exposure were excluded from REACH and no controlled studies were identified by the ERG for these patient groups. The ERG had concerns about the structure of the economic model submitted by the manufacturer, which did not allow improvement in quality of life from treatment while in a progressed state. The manufacturer's model further assumed a divergence in cumulative deaths between the R-FC and FC treatment arms from the outset, which did not accord with observed data from REACH. When the survival advantage was removed, the manufacturer's base-case incremental cost-effectiveness ratio (ICER) changed from 15,593 pounds to between 40,000 pounds and 42,000 pounds per quality-adjusted life-year (QALY). With no survival advantage, the ICER became sensitive to changes in utility. There was no good empirical evidence on the utility of CLL patients in different states. Allowing for the possibility of a survival advantage with rituximab (although not supported by current evidence), the ERG performed further modelling, which found that rituximab would be cost-effective at 20,000 pounds/QALY (30,000 pounds/QALY) if a reduction in survival advantage relative to the manufacturer's base case of 40% (80%) was assumed. The guidance issued by NICE in July 2010 as a result of the STA recommends rituximab with FC for people with relapsed or refractory chronic lymphocytic leukaemia, except when the condition is refractory to fludarabine or where there has been previous treatment with rituximab.

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

Advanced refractory-metal and process technology for the fabrication of x-ray masks

NASA Astrophysics Data System (ADS)

Brooks, Cameron J.; Racette, Kenneth C.; Lercel, Michael J.; Powers, Lynn A.; Benoit, Douglas E.

1999-06-01

This paper provides an in-depth report of the advanced materials and process technology being developed for x-ray mask manufacturing at IBM. Masks using diamond membranes as replacement for silicon carbide are currently being fabricated. Alternate tantalum-based absorbers, such as tantalum boron, which offer improved etch resolution and critical dimension control, as well as higher x-ray absorption, are also being investigated. In addition to the absorber studies, the development of conductive chromium- based hard-mask films to replace the current silicon oxynitride layer is being explored. The progress of this advanced-materials work, which includes significant enhancements to x-ray mask image-placement performance, will be outlined.

Refractory Metal Heat Pipe Life Test - Test Plan and Standard Operating Procedures

NASA Technical Reports Server (NTRS)

Martin, J. J.; Reid, R. S.

2010-01-01

Refractory metal heat pipes developed during this project shall be subjected to various operating conditions to evaluate life-limiting corrosion factors. To accomplish this objective, various parameters shall be investigated, including the effect of temperature and mass fluence on long-term corrosion rate. The test series will begin with a performance test of one module to evaluate its performance and to establish the temperature and power settings for the remaining modules. The performance test will be followed by round-the-clock testing of 16 heat pipes. All heat pipes shall be nondestructively inspected at 6-month intervals. At longer intervals, specific modules will be destructively evaluated. Both the nondestructive and destructive evaluations shall be coordinated with Los Alamos National Laboratory. During the processing, setup, and testing of the heat pipes, standard operating procedures shall be developed. Initial procedures are listed here and, as hardware is developed, will be updated, incorporating findings and lessons learned.

The kinetics of unmatched and HLA-matched 111in-labelled homologous platelets in recipients with chronic marrow hypoplasia and anti-platelet immunity.

PubMed

Peters, A M; Porter, J B; Saverymuttu, S H; Malik, F; Zuiable, A; Lavender, J P; Schwarz, G; Lewis, S M; Gordon-Smith, E C

1985-05-01

The kinetics of homologous platelets, labelled in plasma with 111In-tropolonate, have been studied in five recipients with chronic marrow hypoplasia and severe thrombocytopenia, who were refractory to platelet transfusions as a result of alloimmunization. Mean platelet life span (MPLS), recovery, plasma 111In level and splenic and hepatic uptake kinetics were studied on two occasions, one using HLA-matched platelets and the other unmatched platelets. In each case, recovery of labelled platelets at 1 h post-injection and MPLS improved with HLA matching, although this improvement was highly variable. Only two of the five subjects would have derived any significant benefit from HLA-matched as compared with unmatched platelet transfusions. It was concluded that the need exists for additional cross-matching procedures, possibly related to platelet specific antigens, in patients who remain refractory to platelet transfusion.

Microstructure and Properties of Zircon-Added Carbon Refractories for Blast Furnace

NASA Astrophysics Data System (ADS)

Zhu, Tianbin; Li, Yawei; Sang, Shaobai; Chen, Xilai; Zhao, Lei; Li, Yuanbing; Li, Shujing

2012-11-01

Microstructure and properties of zircon-added carbon refractory specimens for blast furnace (BF) were investigated with the aid of X-ray diffraction (XRD), a scanning electron microscope (SEM), energy-dispersive X-ray, mercury porosimetry, and a laser thermal conductivity (TC) meter. Additives could influence the matrix structures and improve the properties of specimens. With the increase of zircon powder content, the amount of SiC whiskers formed increased and their aspect ratio became larger, and the SiC whiskers tended to be distributed homogeneously. Zircon powder additions decreased the mean pore diameter and increased <1- μm pore volume by filling in pores via SiC, improved the TC and the cold crushing strength (CCS) due to the in-situ formation of the more well-developed SiC whiskers with high TC, and significantly reduced the molten iron attack to carbon specimens.

A Review of Autologous Stem Cell Transplantation in Lymphoma.

PubMed

Zahid, Umar; Akbar, Faisal; Amaraneni, Akshay; Husnain, Muhammad; Chan, Onyee; Riaz, Irbaz Bin; McBride, Ali; Iftikhar, Ahmad; Anwer, Faiz

2017-06-01

Chemotherapy remains the first-line therapy for aggressive lymphomas. However, 20-30% of patients with non-Hodgkin lymphoma (NHL) and 15% with Hodgkin lymphoma (HL) recur after initial therapy. We want to explore the role of high-dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) for these patients. There is some utility of upfront consolidation for-high risk/high-grade B-cell lymphoma, mantle cell lymphoma, and T-cell lymphoma, but there is no role of similar intervention for HL. New conditioning regimens are being investigated which have demonstrated an improved safety profile without compromising the myeloablative efficiency for relapsed or refractory HL. Salvage chemotherapy followed by HDT and rescue autologous stem cell transplant remains the standard of care for relapsed/refractory lymphoma. The role of novel agents to improve disease-related parameters remains to be elucidated in frontline induction, disease salvage, and high-dose consolidation or in the maintenance setting.

Condensation of refractory metals in asymptotic giant branch and other stellar environments

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

Schwander, D.; Berg, T.; Schönhense, G.

2014-09-20

The condensation of material from a gas of solar composition has been extensively studied, but less so condensation in the environment of evolved stars, which has been mainly restricted to major compounds and some specific element groups such as the Rare Earth elements. Also of interest, however, are refractory metals like Mo, Ru, Os, W, Ir, and Pt, which may condense to form refractory metal nuggets (RMNs) like the ones that have been found in association with presolar graphite. We have performed calculations describing the condensation of these elements in the outflows of s-process enriched AGB stars as well asmore » from gas enriched in r-process products. While in carbon-rich environments (C > O), the formation of carbides is expected to consume W, Mo, and V (Lodders and Fegley), the condensation sequence for the other refractory metals under these conditions does not significantly differ from the case of a cooling gas of solar composition. The composition in detail, however, is significantly different due to the completely different source composition. Condensation from an r-process enriched source differs less from the solar case. Elemental abundance ratios of the refractory metals can serve as a guide for finding candidate presolar grains among the RMNs in primitive meteorites—most of which have a solar system origin—for confirmation by isotopic analysis. We apply our calculations to the case of the four RMNs found by Croat et al., which may very well be presolar.« less

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

PubMed

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

2018-01-01

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

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

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

40 CFR 60.141 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Primary Emissions from Basic Oxygen... A of this part. (a) Basic oxygen process furnace (BOPF) means any furnace with a refractory lining... additions into a vessel and introducing a high volume of oxygen-rich gas. Open hearth, blast, and...

40 CFR 60.141 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Primary Emissions from Basic Oxygen... A of this part. (a) Basic oxygen process furnace (BOPF) means any furnace with a refractory lining... additions into a vessel and introducing a high volume of oxygen-rich gas. Open hearth, blast, and...

40 CFR 60.141 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Primary Emissions from Basic Oxygen... A of this part. (a) Basic oxygen process furnace (BOPF) means any furnace with a refractory lining... additions into a vessel and introducing a high volume of oxygen-rich gas. Open hearth, blast, and...

40 CFR 60.141 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Primary Emissions from Basic Oxygen... A of this part. (a) Basic oxygen process furnace (BOPF) means any furnace with a refractory lining... additions into a vessel and introducing a high volume of oxygen-rich gas. Open hearth, blast, and...

40 CFR 60.141 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Primary Emissions from Basic Oxygen... A of this part. (a) Basic oxygen process furnace (BOPF) means any furnace with a refractory lining... additions into a vessel and introducing a high volume of oxygen-rich gas. Open hearth, blast, and...

Maintenance ECT as a therapeutic approach to medication-refractory epilepsy in an adult with mental retardation: case report and review of literature.

PubMed

Shah, Nilesh; Pande, Nikhil; Bhat, Tushar; Murke, Mukund; Andrade, Chittaranjan

2012-06-01

Electroconvulsive therapy (ECT) raises the seizure threshold. This physiological change may benefit patients with seizure disorders. Whereas ECT has recently been used to terminate medication-refractory status epilepticus, there is little current literature on its planned administration as a specific maintenance treatment for medication-refractory epilepsy. We used maintenance ECT to treat an 18-year-old man with a long-standing generalized tonic-clonic seizure disorder who had shown poor response to several antiepileptic drugs administered in combination with antiepileptic medication compliance confirmed through drug level monitoring. A total of 52 ECTs were administered across nearly 20 months at a mean frequency of once in nearly 12 days. From the very outset, ECT dramatically decreased the frequency of spontaneous seizures from approximately 6 to 24 per week at baseline to approximately 1 to 2 per week after ECT initiation. The efficacy of maintenance ECT in spontaneous seizure prophylaxis was greater when the ECT treatment interval was narrower. Improvement with ECT was associated with improved behavior and improved psychosocial functioning on clinical report. No cognitive or other adverse effects were reported or clinically ascertained. The ECT charge administered at the last 10 treatment sessions was 1434 millicoulombs. This is probably the highest electrical stimulus dose recorded in literature. Maintenance ECT may reduce the frequency of breakthrough seizures in patients with seizure disorder that is inadequately responsive to antiepileptic medication regimes. Very high ECT seizure thresholds may be observed when many antiepileptic drugs are concurrently administered in high doses.

Sacral neuromodulation for the treatment of neurogenic lower urinary tract dysfunction caused by multiple sclerosis: a single-centre prospective series.

PubMed

Engeler, Daniel S; Meyer, Daniel; Abt, Dominik; Müller, Stefanie; Schmid, Hans-Peter

2015-10-23

Sacral neuromodulation is well established in the treatment of refractory, non-neurogenic lower urinary tract dysfunction, but its efficacy and safety in patients with lower urinary tract dysfunction of neurological origin is unclear. Only few case series have been reported for multiple sclerosis. We prospectively evaluated the efficacy and safety of sacral neuromodulation in patients with multiple sclerosis. Seventeen patients (13 women, 4 men) treated with sacral neuromodulation for refractory neurogenic lower urinary tract dysfunction caused by multiple sclerosis were prospectively enrolled (2007-2011). Patients had to have stable disease and confirmed neurogenic lower urinary tract dysfunction. Voiding variables, adverse events, and subjective satisfaction were assessed. Sixteen (94 %) patients had a positive test phase with a >70 % improvement. After implantation of the pulse generator (InterStim II), the improvement in voiding variables persisted. At 3 years, the median voided volume had improved significantly from 125 (range 0 to 350) to 265 ml (range 200 to 350) (p < 0.001), the post void residual from 170 (range 0 to 730) to 25 ml (range 0 to 300) (p = 0.01), micturition frequency from 12 (range 6 to 20) to 7 (range 4 to 12) (p = 0.003), and number of incontinence episodes from 3 (range 0 to 10) to 0 (range 0 to 1) (p = 0.006). The median subjective degree of satisfaction was 80 %. Only two patients developed lack of benefit. No major complications occurred. Chronic sacral neuromodulation promises to be an effective and safe treatment of refractory neurogenic lower urinary tract dysfunction in selected patients with multiple sclerosis.

Development of a mercury electromagnetic centrifugal pump for the SNAP-8 refractory boiler development program

NASA Technical Reports Server (NTRS)

Fuller, R. A.; Schnacke, A. W.

1974-01-01

An electromagnetic pump, in which pressure is developed in mercury because of the interaction of the magnetic field and current which flows as a result of the voltage induced in the mercury contained in the pump duct, was developed for the SNAP-8 refractory boiler test facility. Pump performance results are presented for ten duct configurations and two stator sizes. These test results were used to design and fabricate a pump which met the SNAP-8 criteria of 530 psi developed pressure at 12,500 lb/hr. The pump operated continuously for over 13,000 hours without failure or performance degradation. Included in this report are descriptions of the experimental equipment, measurement techniques, all experimental data, and an analysis of the electrical losses in the pump.

Primary conjunctival follicular lymphoma mimicking chronic conjunctivitis.

PubMed

Labrador Velandia, S; García Lagarto, E; Saornil, M A; García Álvarez, C; Cuello, R; Diezhandino, P

2016-02-01

The case is presented of a 43 year-old male patient with chronic follicular conjunctivitis, negative bacterial serology, and refractory to local treatment. The incisional biopsy performed showed to be consistent with reactive lymphoid hyperplasia. A year later, a new incisional biopsy showed follicular lymphoma, with no systemic involvement, and he was treated with local radiotherapy. When a chronic follicular conjunctivitis is refractory to treatment, it is essential to perform an incisional biopsy to establish the histopathological diagnosis that can range from chronic inflammation, reactive lymphoid hyperplasia to lymphoma. Follicular lymphoma is rare among conjunctival lymphomas, and the staging is indispensable for the correct therapeutic approach. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Immediate improvement of motor function after epilepsy surgery in congenital hemiparesis.

PubMed

Pascoal, Tharick; Paglioli, Eliseu; Palmini, André; Menezes, Rafael; Staudt, Martin

2013-08-01

Hemispherectomy often leads to a loss of contralateral hand function. In some children with congenital hemiparesis, however, paretic hand function remains unchanged. An immediate improvement of hand function has never been reported. A 17-year-old boy with congenital hemiparesis and therapy-refractory seizures due to a large infarction in the territory of the middle cerebral artery underwent epilepsy surgery. Intraoperatively, electrical cortical stimulation of the affected hemisphere demonstrated preserved motor projections from the sensorimotor cortex to the (contralateral) paretic hand. A frontoparietal resection was performed, which included a complete disconnection of all motor projections originating in the sensorimotor cortex of the affected hemisphere. Surprisingly, the paretic hand showed a significant functional improvement immediately after the operation. This observation demonstrates that, in congenital hemiparesis, crossed motor projections from the affected hemisphere are not always beneficial, but can be dysfunctional, interfering with ipsilateral motor control over the paretic hand by the contralesional hemisphere. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Laser CO2 treatment for vulvar lymphedema secondary to gynecological cancer therapy: A report of two cases and review of the literature.

PubMed

Sopracordevole, Francesco; Mancioli, Francesca; Canzonieri, Vincenzo; Buttignol, Monica; Giorda, Giorgio; Ciavattini, Andrea

2015-04-01

Vulvar lymphedema is an uncommon and disabling side-effect of pelvic lymphadenectomy and pelvic radiotherapeutic treatment for invasive genital cancer. Lymphorrhea, a complication of lymphedema, may be extremely distressing for patients due to the requirement to wear sanitary towels and as the pain and loss of elasticity of the vulvar skin and mucosa can cause discomfort during coitus. Surgical treatments of lymphorrhea and vulvar lymphedema secondary to gynecological cancer treatments remain controversial and are not currently considered to be the standard therapy. The present study reports two cases of vulvar lymphedema complicated by vulvar lymphorrhea in females who had undergone treatment for cervical and endometrial cancer, respectively; a review of the literature is also included. In the two present cases, vulvar lymphedemas were refractory to standard treatments, including decongestive therapy, manual lymph drainage, elastic bandaging, low-stretch bandaging, exercises and skin care. Laser CO 2 excision and vaporization of the whole skin and mucosal tissue of the vulva was successfully performed to treat the lymphorrhea and improve quality of life. Thus, the present two cases indicated that laser CO 2 surgery may present an additional therapy for the treatment of genital lymphedema that is refractory to other treatments.

Iodine-131 Metaiodobenzylguanidine Therapy for Neuroblastoma: Reports So Far and Future Perspective

PubMed Central

Kayano, Daiki

2015-01-01

Neuroblastoma, which derives from neural crest, is the most common extracranial solid cancer in childhood. The tumors express the norepinephrine (NE) transporters on their cell membrane and take in metaiodobenzylguanidine (MIBG) via a NE transporter. Since iodine-131 (I-131) MIBG therapy was firstly reported, many trails of MIBG therapy in patients with neuroblastoma were performed. Though monotherapy with a low dose of I-131 MIBG could achieve high-probability pain reduction, the objective response was poor. In contrast, more than 12 mCi/kg I-131 MIBG administrations with or without hematopoietic cell transplantation (HCT) obtain relatively good responses in patients with refractory or relapsed neuroblastoma. The combination therapy with I-131 MIBG and other modalities such as nonmyeloablative chemotherapy and myeloablative chemotherapy with HCT improved the therapeutic response in patients with refractory or relapsed neuroblastoma. In addition, I-131 MIBG therapy incorporated in the induction therapy was proved to be feasible in patients with newly diagnosed neuroblastoma. To expand more the use of MIBG therapy for neuroblastoma, further studies will be needed especially in the use at an earlier stage from diagnosis, in the use with other radionuclide formations of MIBG, and in combined use with other therapeutic agents. PMID:25874239

Successful early romiplostim use in a case of severe immune thrombocytopenia with critical carotid arterial injury.

PubMed

Watanabe, Reiko; Tabayashi, Takayuki; Tomikawa, Tatsuki; Sagawa, Morihiko; Anan-Nemoto, Tomoe; Kimura, Yuta; Takahashi, Yasuyuki; Tokuhira, Michihide; Otaki, Satoshi; Oi, Hidenori; Sawano, Makoto; Sugiyama, Satoshi; Kizaki, Masahiro

2017-01-01

Thrombopoietin receptor (TPO-R) agonists have been shown to be effective in refractory chronic immune thrombocytopenia (ITP); however, their efficacy in patients under critical care is not known. We report the case of a female patient with a newly diagnosed ITP who experienced severe bleeding from an external wound. The patient was administered the standard treatments for ITP, which are high-dose intravenous immunoglobulin (IVIg) and corticosteroids. However, following failure of these treatments, we administered romiplostim on day 6 after the onset of ITP. On day 6 after the initiation of romiplostim, there was improvement in platelet count and bleeding tendency. We were subsequently able to perform a splenectomy successfully. The efficacy of TPO-R agonists in ITP has been reported in several situations, including before surgery in an ITP patient; however, the use of TPO-R for arterial bleeding with shock has not been reported. To our knowledge, the present article is a rare case report of the use of a TPO-R agonist in a patient with critical artery injury. Our data suggest that the early use of romiplostim is effective in emergency cases of newly diagnosed ITP with life-threatening bleeding, which is refractory to standard treatment.

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

Ibrutinib Improves Survival in Patients with Previously Treated Chronic Lymphocytic Leukemia

Cancer.gov

A summary of results from an international phase III trial that compared ibrutinib (Imbruvica®) and ofatumumab (Arzerra®) for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Cardiorenal outcomes after slow continuous ultrafiltration therapy in refractory patients with advanced decompensated heart failure.

PubMed

Patarroyo, Maria; Wehbe, Edgard; Hanna, Mazen; Taylor, David O; Starling, Randall C; Demirjian, Sevag; Tang, W H Wilson

2012-11-06

The purpose of this study was to examine the clinical outcomes of using slow continuous ultrafiltration (SCUF) in patients with acute decompensated heart failure (HF) refractory to intensive medical therapy. Several studies have demonstrated the clinical usefulness of early SCUF in patients with acute decompensated HF to improve fluid overload and hemodynamics. We reviewed clinical data from 63 consecutive adult patients with acute decompensated HF admitted to the Heart Failure Intensive Care Unit from 2004 through 2009 who required SCUF because of congestion refractory to hemodynamically guided intensive medical therapy. The mean creatinine level was 1.9 ± 0.8 mg/dl on admission and 2.2 ± 0.9 mg/dl at SCUF initiation. After 48 hours of SCUF, there were significant improvements in hemodynamic variables (mean pulmonary arterial pressure: 40 ± 12 mm Hg vs. 33 ± 8 mm Hg, p = 0.002, central venous pressure: 20 ± 6 mm Hg vs. 16 ± 8 mm Hg, p = 0.007, mean pulmonary wedge pressure: 27 ± 8 mm Hg vs. 20 ± 7 mm Hg, p = 0.02, Fick cardiac index: 2.2 l/min/m(2) [interquartile range: 1.87 to 2.77 l/min/m(2)] vs. 2.6 l/min/m(2) [interquartile range: 2.2 to 2.9 l/min/m(2)], p = 0.0008), and weight loss (102 ± 25 kg vs. 99 ± 23 kg, p < 0.0001). However, there were no significant improvements in serum creatinine levels (2.2 ± 0.9 mg/dl vs. 2.4 ± 1 mg/dl, p = 0.12) and blood urea nitrogen (60 ± 30 mg/dl vs. 60 ± 28 mg/dl, p = 0.97). Fifty-nine percent required conversion to continuous hemodialysis during their hospital course, and 14% were dependent on dialysis at hospital discharge. Thirty percent died during hospitalization, and 6 patients were discharged to hospice care. In our single-center experience, SCUF after admission for acute decompensated HF refractory to standard medical therapy was associated with high incidence of subsequent transition to renal replacement therapy and high in-hospital mortality, despite significant improvement in hemodynamics. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Changes in sexual function of women with refractory interstitial cystitis/bladder pain syndrome after intravesical therapy with a hyaluronic acid solution.

PubMed

Hung, Man-Jung; Su, Tsung-Hsien; Lin, Yi-Hao; Huang, Wen-Chu; Lin, Tzu-Yin; Hsu, Chun-Shuo; Chuang, Fei-Chi; Tsai, Ching-Pei; Shen, Pao-Sheng; Chen, Gin-Den

2014-09-01

Intravesical instillation with a hyaluronic acid (HA) solution is an effective treatment for interstitial cystitis/bladder pain syndrome (IC/BPS), but its impact on sexual functioning of patients is not known. The aim of this study was to evaluate the changes in sexual function of women with refractory IC/BPS who underwent a second-line intravesical HA therapy. A total of 103 women diagnosed with refractory IC/BPS were enrolled in this prospective, multicenter study. Sexual function was evaluated using the short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-9). Bladder-related symptoms and bother were assessed by the Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI), and a pain visual analog scale (VAS), respectively. Data were analyzed with univariate methods or multivariate logistic regression analysis accordingly. Changes in PISQ-9, ICSI, ICPI, and pain VAS scores after treatment were assessed. Mean age and duration of symptoms was 43.6 ± 11.8 and 5.1 ± 5.0 years, respectively. ICSI, ICPI, and pain VAS scores were significantly (P < 0.001) improved after 1 month and 6 months of treatment. Of the 87 (84.5%) sexually active women evaluated, PISQ-9 total scores improved significantly (P < 0.001) from the baseline (mean 18.9 ± 6.4), after 1 month (20.4 ± 5.8), and 6-months (21.5 ± 5.6) of treatment. Significantly improved PISQ-9 items included "dyspareunia" (P < 0.001) and "negative reactions" (P = 0.015) during sexual intercourse, and "intensity" (P < 0.001) of sexual orgasms. After a logistic regression analysis, we found that a baseline PISQ-9 score was negatively correlated with the duration of IC/BPS symptoms (P = 0.022). Meanwhile, the changes in PISQ-9 scores were positively correlated with the reduction in ICSI scores after treatment (P = 0.045). Intravesical HA is an effective treatment for refractory IC/BPS. A longer duration of IC/BPS symptoms may be a predictor of poor sexual function. However, intravesical HA may improve sexual function along with the reduction of IC/BPS symptoms. © 2014 International Society for Sexual Medicine.

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

Clozapine and risperidone in moderately refractory schizophrenia: a 6-month randomized double-blind comparison.

PubMed

Schooler, Nina R; Marder, Stephen R; Chengappa, K N R; Petrides, Georgios; Ames, Donna; Wirshing, William C; McMeniman, Marjorie; Baker, Robert W; Parepally, Haranath; Umbricht, Daniel; Kane, John M

2016-05-01

Clozapine remains the only medication indicated for refractory schizophrenia. As new antipsychotic drugs become available, their efficacy compared to clozapine, particularly in moderately ill patients, is of great clinical interest. We compared risperidone, the first of these, to clozapine in partially responsive patients. Further, since participation of patients usually excluded from clinical trials is increasingly important, we broadened inclusion to a wider patient population. We compared clozapine (n = 53) to risperidone (n = 54) in a randomized, double-blind, 29-week trial in schizophrenia patients (diagnosed using DSM-IV) at 3 research outpatient clinics. Randomization was stratified by "narrow" or "broad" inclusion criteria. The study was conducted between December 1995 and October 1999. Time to treatment discontinuation for lack of efficacy and time to 20% improvement in the Brief Psychiatric Rating Scale psychotic symptom cluster were the primary outcome measures. There were no differences in all-cause discontinuation; clozapine-treated participants were significantly less likely to discontinue for lack of efficacy (15%) than risperidone-treated participants (38%) (Wilcoxon χ(2)1 = 6.10, P = .01). Clozapine resulted in significantly more global improvement (F2,839 = 6.07, P < .01) and asociality improvement (F2,315 = 6.64, P < .01) than risperidone. There was no difference in proportions meeting an a priori criterion of psychosis improvement (risperidone: 57%; clozapine: 71%). Significant adverse effect differences in salivation (F1 = 4.05, P < .05) (F1 = 12.13, P < .001), sweating (F1 = 5.07, P < .05), and tachycardia (F1 = 6.51, P < .05) favored risperidone. Clozapine-treated partially responsive patients were less likely to discontinue treatment for lack of efficacy and improved more globally than those treated with risperidone, although psychotic symptoms did not differ. These findings suggest that clozapine should not be restricted to the most severely ill, treatment-refractory patients; it should be considered as an alternative for patients who have some response to other antipsychotics, but still experience troubling symptoms. © Copyright 2016 Physicians Postgraduate Press, Inc.

The ketogenic diet is effective for refractory epilepsy associated with acquired structural epileptic encephalopathy.

PubMed

Villaluz, Mel Michel; Lomax, Lysa Boissé; Jadhav, Trupti; Cross, J Helen; Scheffer, Ingrid E

2018-07-01

Ketogenic diet therapies have proven efficacy for refractory epilepsy. There are many reports of their use in the genetic developmental and epileptic encephalopathies; however, little attention has been paid as to whether the diet is also effective in individuals with an acquired structural aetiology. We observed remarkable efficacy of the diet in two patients with hypoxic-ischaemic encephalopathy. We then analysed our cases with refractory structural epilepsies of acquired origin to characterize their response to the ketogenic diet. The classical ketogenic diet was implemented with dietary ratios of 3:1 to 4.4:1. Seizure frequency at 1 month, 3 months, 6 months, 1 year, and 2 years was ascertained. A responder was defined as greater than 50% seizure reduction compared to baseline. Seven of the nine patients were responders at 3 months. Somewhat surprisingly we found that the ketogenic diet was effective in patients with a developmental and epileptic encephalopathy due to an acquired structural aetiology. This cohort may not be routinely considered for the ketogenic diet because of their structural and acquired, rather than genetic, basis. The ketogenic diet should be considered early in the management of patients with acquired structural encephalopathies as it can improve seizure control with the potential to improve developmental outcome. The ketogenic diet was effective in children with epilepsy associated with an acquired structural aetiology. © 2018 Mac Keith Press.

Production of crystalline refractory metal oxides containing colloidal metal precipitates and useful as solar-effective absorbers

DOEpatents

Narayan, Jagdish; Chen, Yok

1983-01-01

This invention is a new process for producing refractory crystalline oxides having improved or unusual properties. The process comprises the steps of forming a doped-metal crystal of the oxide; exposing the doped crystal in a bomb to a reducing atmosphere at superatmospheric pressure and a temperature effecting precipitation of the dopant metal in the crystal lattice of the oxide but insufficient to effect net diffusion of the metal out of the lattice; and then cooling the crystal. Preferably, the cooling step is effected by quenching. The process forms colloidal precipitates of the metal in the oxide lattice. The process may be used, for example, to produce thermally stable black MgO crystalline bodies containing magnetic colloidal precipitates consisting of about 99% Ni. The Ni-containing bodies are solar-selective absorbers, having a room-temperature absorptivity of about 0.96 over virtually all of the solar-energy spectrum and exhibiting an absorption edge in the region of 2 .mu.m. The process parameters can be varied to control the average size of the precipitates. The process can produce a black MgO crystalline body containing colloidal Ni precipitates, some of which have the face-centered-cubic structure and others of which have the body-centered cubic structure. The products of the process are metal-precipitate-containing refractory crystalline oxides which have improved or unique optical, mechanical, magnetic, and/or electronic properties.

Productivity costs decrease after endoscopic sinus surgery for refractory chronic rhinosinusitis.

PubMed

Rudmik, Luke; Smith, Timothy L; Mace, Jess C; Schlosser, Rodney J; Hwang, Peter H; Soler, Zachary M

2016-03-01

The primary objective of this pilot study was to define the change in productivity costs following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). Secondary objectives were to identify CRS-related characteristics that may influence the degree of productivity improvement after ESS. Prospective, multi-institutional, observational cohort study. The human capital approach was used to define productivity costs. Annual absenteeism, presenteeism, and lost leisure time were quantified to define annual lost productive time (LPT). LPT was monetized using the annual daily wage rates obtained from the 2012 US Census and the 2013 US Department of Labor statistics. Twenty-seven patients with refractory CRS who underwent ESS were followed for a mean of 15 months (range, 8-25 months). Following ESS, there were improvements in annual absenteeism (22 days reduced to 3 days), annual presenteeism (41 days reduced to 19 days), and annual household days lost (12 days reduced to 6 days). Overall, the preoperative productivity costs were reduced after ESS ($9,190 vs. $3,373, respectively; P < .001). Daily productivity is negatively impacted by the presence of CRS. The outcomes from this study provide the first insights into the reduced productivity costs associated with receiving ESS for refractory CRS. Future studies with larger sample sizes will need to validate the results from this pilot study. 2c Laryngoscope, 126:570-574, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Productivity Costs Decrease After Endoscopic Sinus Surgery for Refractory Chronic Rhinosinusitis

PubMed Central

Rudmik, Luke; Smith, Timothy L.; Mace, Jess C.; Schlosser, Rodney J.; Hwang, Peter H.; Soler, Zachary M.

2015-01-01

Objective The primary objective of this pilot study was to define the change in productivity costs following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). Secondary objectives were to identify CRS-related characteristics that may influence the degree of productivity improvement after ESS. Study Design Prospective, multi-institutional, observational cohort study. Methods The human capital approach was used to define productivity costs. Annual absenteeism, presenteeism, and lost leisure time was quantified to define annual lost productive time (LPT). LPT was monetized using the annual daily wage rates obtained from the 2012 US National Census and the 2013 US Department of Labor statistics. Results 27 patients with refractory CRS who underwent ESS were followed for a mean of 15 [SD 4.0] months (range: 8 – 25 months). Following ESS, there were improvements in annual absenteeism (22 days reduced to 3 days), annual presenteeism (41 days reduced to 19 days), and annual household days lost (12 days reduced to 6 days). Overall, the preoperative productivity costs were reduced after ESS, $9,097 vs. $3,301, respectively (p<0.001). Conclusion Daily productivity is negatively impacted by the presence of CRS. The outcomes from this study provide the first insights into the reduced productivity costs associated with receiving ESS for refractory CRS. Future studies with larger sample sizes will need to validate the results from this pilot study. PMID:26371457

Advanced refractory metals and composites for extraterrestrial power systems

NASA Technical Reports Server (NTRS)

Titran, R. H.; Grobstein, Toni L.

1990-01-01

Concepts for future space power systems include nuclear and focused solar heat sources coupled to static and dynamic power-conversion devices; such systems must be designed for service lives as long as 30 years, despite service temperatures of the order of 1600 K. Materials are a critical technology-development factor in such aspects of these systems as reactor fuel containment, environmental protection, power management, and thermal management. Attention is given to the prospective performance of such refractory metals as Nb, W, and Mo alloys, W fiber-reinforced Nb-matrix composites, and HfC precipitate-strengthened W-Re alloys.

Vagal nerve stimulator: Evolving trends

PubMed Central

Ogbonnaya, Sunny; Kaliaperumal, Chandrasekaran

2013-01-01

Over three decades ago, it was found that intermittent electrical stimulation from the vagus nerve produces inhibition of neural processes, which can alter brain activity and terminate seizures. This paved way for the concept of vagal nerve stimulator (VNS). We describe the evolution of the VNS and its use in different fields of medicine. We also review the literature focusing on the mechanism of action of VNS producing desired effects in different conditions. PUBMED and EMBASE search was performed for ‘VNS’ and its use in refractory seizure management, depression, obesity, memory, and neurogenesis. VNS has been in vogue over for the past three decades and has proven to reduce the intensity and frequency of seizure by 50% in the management of refractory seizures. Apart from this, VNS has been shown to promote neurogenesis in the dentate gyrus of rat hippocampus after 48 hours of stimulation of the vagus nerve. Improvement has also been observed in non-psychotic major depression from a randomized trial conducted 7 years ago. The same concept has been utilized to alter behavior and cognition in rodents, and good improvement has been observed. Recent studies have proven that VNS is effective in obesity management in patients with depression. Several hypotheses have been postulated for the mechanism of action of VNS contributing to its success. VNS has gained significant popularity with promising results in epilepsy surgery and treatment-resistant depression. The spectrum of its use has also extended to other fields of medicine including obesity, memory, and neurogenesis, and there is still a viable scope for its utility in the future. PMID:23633829

Oral sirolimus: A possible treatment for refractory angina pectoris in the elderly.

PubMed

Mischie, Alexandru; Chanseaume, Sylvain; Gaspard, Philippe; Andrei, Catalina Liliana; Sinescu, Crina; Schiariti, Michele

2016-11-01

Refractory angina pectoris (RAP) is a clinical problem, frequently encountered in the elderly, associated with high health-care costs. Until recently, the goal of RAP treatment aimed at improving the quality of life (QoL) because it was thought that mortality rates were not different between stable angina pectoris and RAP. Our purpose was at determining whether any mortality rate difference exists and whether any novel therapeutical solution might be translated into clinical practice. We therefore performed a literature review to assess current optimal treatment of RAP patients, including all studies involving the use of oral sirolimus and stents, although no consistent evidence was found for any specific treatment to improve survival, apart from minor QoL amelioration. A large mortality difference was seen between RAP and stable angina pectoris. On the other hand, therapeutic approaches to RAP patients showed frequent complications and several contraindications, depending on the procedure. We propose to inhibit instead of stimulating angiogenesis, by giving oral sirolimus, an immunosuppressive drug, thereby decreasing the atherosclerotic process and its evolution. Sirolimus was shown to decrease left ventricular mass (thus indirectly decreasing myocardial oxygen needs and consumption). It might stop and, in some cases, even enable regression of plaque progression. Sirolimus side effects are mild to moderate and wash-out rapidly at treatment discontinuation. Compared with current therapies sirolimus treatment is more health-care cost efficient. It should be important to design a trial in RAP patients powered to reduce mortality and QoL increase. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A Functional-Genetic Scheme for Seizure Forecasting in Canine Epilepsy.

PubMed

Bou Assi, Elie; Nguyen, Dang K; Rihana, Sandy; Sawan, Mohamad

2018-06-01

The objective of this work is the development of an accurate seizure forecasting algorithm that considers brain's functional connectivity for electrode selection. We start by proposing Kmeans-directed transfer function, an adaptive functional connectivity method intended for seizure onset zone localization in bilateral intracranial EEG recordings. Electrodes identified as seizure activity sources and sinks are then used to implement a seizure-forecasting algorithm on long-term continuous recordings in dogs with naturally-occurring epilepsy. A precision-recall genetic algorithm is proposed for feature selection in line with a probabilistic support vector machine classifier. Epileptic activity generators were focal in all dogs confirming the diagnosis of focal epilepsy in these animals while sinks spanned both hemispheres in 2 of 3 dogs. Seizure forecasting results show performance improvement compared to previous studies, achieving average sensitivity of 84.82% and time in warning of 0.1. Achieved performances highlight the feasibility of seizure forecasting in canine epilepsy. The ability to improve seizure forecasting provides promise for the development of EEG-triggered closed-loop seizure intervention systems for ambulatory implantation in patients with refractory epilepsy.

Design of Refractory Linings for Balanced Energy Efficiency, Uptime, and Capacity in Lime Kilns

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

Gorog, John Peter; Hemrick, James Gordon; Walker, Harold

2014-01-01

The rotary kilns used by the pulp and paper industry to regenerate lime in the Kraft process are very energy intensive. Throughout the 90 s, in response to increasing fuel prices, the industry used back up insulation in conjunction with the high alumina brick used to line the burning zones of their kilns. While this improved energy efficiency, the practice of installing insulating brick behind the working lining increased the inner wall temperatures. In the worst case, due to the increased temperatures, rapid brick failures occurred causing unscheduled outages and expensive repairs. Despite these issues, for the most part, themore » industry continued to use insulating refractory linings in that the energy savings were large enough to offset any increase in the cost of maintaining the refractory lining. Due to the dramatic decline in the price of natural gas in some areas combined with mounting pressures to increasing production of existing assets, over the last decade, many mills are focusing more on increasing the uptime of their kilns as opposed to energy savings. To this end, a growing number of mills are using basic (magnesia based) brick instead of high alumina brick to line the burning zone of the kiln since the lime mud does not react with these bricks at the operating temperatures of the burning zone of the kiln. In the extreme case, a few mills have chosen to install basic brick in the front end of the kiln running a length equivalent to 10 diameters. While the use of basic brick can increase the uptime of the kiln and reduce the cost to maintain the refractory lining, it does dramatically increase the heat losses resulting from the increased operating temperatures of the shell. Also, over long periods of time operating at these high temperatures, damage can occur in the shell. There are tradeoffs between energy efficiency, capacity and uptime. When fuel prices are very high, it makes sense to insulate the lining. When fuel prices are lower, trading some thermal efficiency for increased uptime and capacity seems reasonable. This paper considers a number of refractory linings in an effort to develop optimized operating strategies that balance these factors. In addition to considering a range of refractory materials, the paper examines other factors such as the chain area, discharge dams and other operating variables that impact the service life of the refractory lining. The paper provides recommendations that will help mill personnel develop a strategy to select a refractory lining that is optimized for their specific situation.« less

Supra-Tenon Capsule Implantation of the Ahmed Glaucoma Valve in Refractory Pediatric Glaucoma.

PubMed

Elhefney, Eman M; Al-Sharkawy, Hossam T; Kishk, Hanem M

2016-09-01

To evaluate the efficacy of supra-Tenon capsule implantation of an Ahmed glaucoma valve (AGV) as a measure to decrease the fibrotic potential of the Tenon capsule on bleb formation and its subsequent effect on intraocular pressure (IOP) control in children with refractory glaucoma. Mansoura Ophthalmic Centre, Faculty of Medicine, Mansoura University, Egypt. A prospective interventional study. Twenty-two eyes of 12 children with refractory glaucoma underwent supra-Tenon capsule implantation of AGV. Ophthalmic examinations under general anesthesia including measurement of the corneal diameter and the IOP with Perkin's tonometer were performed preoperatively, on the first postoperative day, the first postoperative week, weekly for the first month, 2-weekly for the following 3 months, and monthly for at least 18 months. Postoperative complications and the number of glaucoma medications used preoperatively and postoperatively were recorded. The paired Student t test was used to compare preoperative and postoperative data. There were 12 eyes (54.6%) with refractory congenital glaucoma, 7 eyes (31.8%) with refractory pseudophakic glaucoma, and 3 eyes (13.6%) with refractory aphakic glaucoma. Patients included 10 male (83.3%) and 2 female (16.7%) children with a mean age of 16.3±9.7 months. The mean follow-up duration was 24.1±4.3 months. There was a statistically significant difference between the mean preoperative IOP (30.7±2.88 mm Hg) and the mean postoperative IOP (16.1±3.60 mm Hg) (t=16.22 and P=0.000, with a mean decrease in the IOP by 47.6%). The difference between the mean number of antiglaucoma medications before surgery (1.86±0.4) and after surgery (1.0±0.9) was also statistically significant (t=4.31 and P=0.000). Total success was achieved in 18 eyes (81.9%). Postoperative complications included tube exposure and slippage (10%), hypotony (10%), and hyphema (5%). Supra-Tenon capsule implantation of the AGV was successful in controlling the IOP with few postoperative complications in the management of children with refractory glaucoma.

Does education play a role in language reorganization after surgery in drug refractory temporal lobe epilepsy: An fMRI based study?

PubMed

Chaudhary, Kapil; Ramanujam, Bhargavi; Kumaran, S Senthil; Chandra, P Sarat; Wadhawan, Ashima Nehra; Garg, Ajay; Tripathi, Manjari

2017-10-01

Patients with drug refractory epilepsy (DRE) and a high level of education may differ in their language recovery after surgery. Our aim was to determine whether there were differences in the extent of improvement and pattern of reorganization of language functions on functional magnetic resonance imaging (fMRI) after surgery to treat refractory temporal lobe epilepsy (TLE) between patients with more than 12 years of formal education versus those with a shorter period of regular schooling. After approval by an institutional ethics committee, 60 right-handed, adult patients of left TLE and 20 right-handed, healthy controls were recruited to the study. Multiple aspects of language (Repetition, Naming, Word fluency, Visual word and Comprehension reading) were tested using the Indian Aphasia Battery (IAB) in the Hindi language; fMRI was performed using a standardized Hindi language paradigm (lexical, semantic, syntactic and comprehension components) in both cases and controls, before and after an anterior temporal lobectomy (in cases) with a 1.5T MR Scanner. An array of performance tests of intelligence and the verbal adult intelligence scale (VAIS) were used to measure the Intelligence Quotient (IQ) in Left TLE (LTLE) patients before and after surgery. Language laterality was estimated using the laterality index (LI-toolbox-spm8). Cohen's d test was performed to determine the effect sizes of the differences in the IAB scores, and Pearson's correlation was applied between regional (IFG and STG) activation in controls and TLE patients with more than 12 years of schooling [higher educational status (HES subgroup)] and those with less than 12 years of schooling [lower educational status (LES subgroup)]. At the baseline, clinical testing with IAB showed better scores in controls than in cases. Better scores were observed in subjects with higher levels of education than in those with lower levels of education. An improvement was observed in IQ scores in both the HES and LES groups after ATLR; significant worsening in the abstract ability subtest was noted in the LES group, whereas in the HES group there was an improvement. Blood-oxygen-level dependent (BOLD) activation during language tasks was observed in both cerebral hemispheres in the TLE cases, while it was observed in the traditional left hemispheric language areas in controls. Postoperatively, greater BOLD activation was observed in the left inferior frontal gyri (IFG, r=0.65 * ; p<0.05), middle frontal gyrus (MFG, r=0.77 ** ; p<0.01) superior temporal gyri (STG, r=0.88 * p<0.02) and angular gyrus (AG, r=0.73 * ; p<0.04) in HES compared to LES subjects. Similarly, LI showed left lateralization of the frontal (LIw=0.77 & 0.71) and temporal (LIw=0.74 & 0.5) regions in controls and the TLE group (post-surgery) compared to the pre-surgery group during language tasks. Greater improvement in language skills and BOLD activation in the left hemisphere in TLE-patients (after epilepsy surgery) with a high level of education was similar to that of healthy controls, implying that education has an effect on the functional reorganization/recovery of language areas. Copyright © 2017 Elsevier B.V. All rights reserved.

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

A phase I trial of NK-92 cells for refractory hematological malignancies relapsing after autologous hematopoietic cell transplantation shows safety and evidence of efficacy

PubMed Central

Williams, Brent A.; Law, Arjun Datt; Routy, Bertrand; denHollander, Neal; Gupta, Vikas; Wang, Xing-Hua; Chaboureau, Amélie; Viswanathan, Sowmya; Keating, Armand

2017-01-01

Background Autologous NK cell therapy can treat a variety of malignancies, but is limited by patient-specific variations in potency and cell number expansion. In contrast, allogeneic NK cell lines can overcome many of these limitations. Cells from the permanent NK-92 line are constitutively activated, lack inhibitory receptors and appear to be safe based on two prior phase I trials. Materials and Methods We conducted a single-center, non-randomized, non-blinded, open-label, Phase I dose-escalation trial of irradiated NK-92 cells in adults with refractory hematological malignancies who relapsed after autologous hematopoietic cell transplantation (AHCT). The objectives were to determine safety, feasibility and evidence of activity. Patients were treated at one of three dose levels (1 × 109 cells/m2, 3 × 109 cells/m2 and 5 × 109 cells/m2), given on day 1, 3 and 5 for a planned total of six monthly cycles. Results Twelve patients with lymphoma or multiple myeloma who relapsed after AHCT for relapsed/refractory disease were enrolled in this trial. The treatment was well tolerated, with minor toxicities restricted to acute infusional events, including fever, chills, nausea and fatigue. Two patients achieved a complete response (Hodgkin lymphoma and multiple myeloma), two patients had minor responses and one had clinical improvement on the trial. Conclusions Irradiated NK-92 cells can be administered at very high doses with minimal toxicity in patients with refractory blood cancers, who had relapsed after AHCT. We conclude that high dose NK-92 therapy is safe, shows some evidence of efficacy in patients with refractory blood cancers and warrants further clinical investigation. PMID:29179517

Usefulness of cardiac biomarkers to predict cardiac recovery in patients on extracorporeal membrane oxygenation support for refractory cardiogenic shock.

PubMed

Luyt, Charles-Edouard; Landivier, Antoine; Leprince, Pascal; Bernard, Maguy; Pavie, Alain; Chastre, Jean; Combes, Alain

2012-10-01

No prognostic markers of myocardial recovery in patients with refractory cardiogenic shock requiring circulatory support are known, but early identification of patients who will not recover might provide an opportunity to change the treatment strategy to improve outcome. Because N-terminal fragment of the B-type natriuretic peptide, troponin Ic, midregional fragment of the proatrial natriuretic peptide, proadrenomedullin, and copeptin are prognostic markers in patients with cardiac failure, we hypothesized that, among patients with refractory cardiogenic shock of potentially reversible cause supported with extracorporeal membrane oxygenation (ECMO), the kinetics of these markers might help identify patients who would recover. This was a prospective, observational, single-center study in a medical-surgical intensive care unit. Among 41 consecutive patients with refractory cardiogenic shock of potentially reversible cause receiving ECMO support, 18 recovered and were successfully weaned off the machine. Blood N-terminal fragment of the B-type natriuretic peptide, troponin Ic, midregional fragment of the proatrial natriuretic peptide, proadrenomedullin, and copeptin concentrations were determined on days 1, 3, and 7 post-ECMO. Neither the absolute values of those biomarkers at days 1, 3, or 7 nor their kinetics during the first week differed between patients weaned or not. Areas under the receiver operating characteristic curves (95% confidence interval) of the day 1-to-day 3 biomarker changes for predicting cardiac recovery were 0.54 (0.36-0.71), 0.61 (0.43-0.78), 0.61 (0.42-0.77), 0.56 (0.38-0.73), and 0.61 (0.43-0.78), respectively. In patients with refractory cardiogenic shock of potentially reversible cause receiving ECMO support, early measurements of cardiac biomarkers are not useful for identifying those who would recover. Copyright © 2012 Elsevier Inc. All rights reserved.

[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.

Response to parenteral iron therapy distinguish unexplained refractory iron deficiency anemia from iron-refractory iron deficiency anemia.

PubMed

Akin, M; Sarbay, H; Guler, S; Balci, Y I; Polat, A

2016-04-01

We evaluated that response to parenteral iron therapy could be helpful in distinguishing the types of iron deficiency anemia. This study analyzed responses to IV iron sucrose therapy of 15 children with unexplained refractory iron deficiency anemia (URIDA). We compared the results at diagnosis, 6 weeks and 6 months after the therapy. Results were compared with responses of 11 patients' results with iron-refractory iron deficiency anemia (IRIDA) from our previous study. Six weeks after the start of treatment, ferritin, MCV, MCH and Hb values were in normal range in 10 patients. The increase in Hb, MCH, MCV, and ferritin values ranged 2.6-3.5 g/dL, 1.7-4.2 pg, 2-9 fL, and 13-25 ng/mL, respectively. In five patients, Hb, MCH, and MCV mean (range) values [11.2 g/dL (11-12.2), 24.5 pg (24-25.6), and 67 fL (65-70)] were nearly normal but ferritin mean (range) values [9.8 ng/mL (8-11)] were below normal. Six weeks after the start of treatment, Hb, MCH, MCV and ferritin values of patients with IRIDA were increased. The increase in Hb, MCH, MCV, and ferritin values ranged 0.8-2.7 g/dL, 1.7-4.2 pg, 2-9 fL, and 13-25 ng/mL, respectively. IRIDA is only partially responsive to parenteral iron supplementation. In conclusion, this study demonstrated that the response to intravenous iron therapy for the URIDA cases improved blood parameters more effectively than hereditary IRIDA. Response to parenteral iron therapy would be helpful to distinguish unexplained refractory IDA from hereditary IRIDA for clinicians who do not have access to hepcidin or TMPRS6 mutation analysis. © 2016 John Wiley & Sons Ltd.

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.

Multicenter study of combination DEP regimen as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis.

PubMed

Wang, Yini; Huang, Wenqiu; Hu, Liangding; Cen, Xinan; Li, Lihong; Wang, Jijun; Shen, Jianliang; Wei, Na; Wang, Zhao

2015-11-05

Hemophagocytic lymphohistiocytosis (HLH) is a refractory immune disorder with a significant risk of death. Although standard therapy has dramatically improved survival in HLH patients, approximately 30%, especially adults, show no response to current treatment strategies. This prospective study aimed to investigate the efficacy of liposomal doxorubicin treatment combined with etoposide and methylprednisolone (doxorubicin-etoposide-methylprednisolone; DEP) as a salvage therapy for adult refractory HLH. Adult patients who did not achieve at least partial response 2 weeks after initial standard HLH therapy were enrolled in this study between June 2013 and June 2014. Response to salvage therapy was assessed at 2 and 4 weeks after initiation of DEP therapy and patients were followed until death or until November 2014. Sixty-three refractory HLH patients were enrolled, including 29 cases of lymphoma-associated HLH, 22 cases of Epstein-Barr virus-associated HLH, and 4 cases of familial HLH. There were 8 cases with unknown underlying diseases. Seventeen cases (27.0%) achieved complete response and 31 cases (49.2%) achieved partial response. The overall response was 76.2% (48/63). Patients who showed no response to DEP died within 4 weeks after salvage therapy. Twenty-nine of the 48 patients who achieved partial or complete response survived to subsequent chemotherapy, allogenic hematopoietic stem cell transplantation, or splenectomy. Our study suggests that DEP regimen is an effective salvage regimen for adult refractory HLH, which can prolong patient survival as we continue to understand the responsible mechanisms and bridge the gap between HLH and its underlying diseases. This study was registered in the Chinese Clinical Trials Registry Platform (http://www.chictr.org.cn/) as ChiCTR-IPC-14005514. © 2015 by The American Society of Hematology.

Value of 3.0 T MR imaging in refractory partial epilepsy and negative 1.5 T MRI.

PubMed

Nguyen, Dang Khoa; Rochette, Emilie; Leroux, Jean-Maxime; Beaudoin, Gilles; Cossette, Patrick; Lassonde, Maryse; Guilbert, François

2010-10-01

High-field 3.0 T MR scanners provide an improved signal-to-noise ratio which can be translated in higher image resolution, possibly allowing critical detection of subtle epileptogenic lesions missed on standard-field 1.0-1.5 T MRIs. In this study, the authors explore the potential value of re-imaging at 3.0 T patients with refractory partial epilepsy and negative 1.5 T MRI. We retrospectively identified all patients with refractory partial epilepsy candidate for surgery who had undergone a 3.0 T MR study after a negative 1.5 T MR study. High-field 3.0 T MRIs were reviewed qualitatively by neuroradiologists experienced in interpreting epilepsy studies with access to clinical information. Relevance and impact on clinical management were assessed by an epileptologist. Between November 2006 and August 2009, 36 patients with refractory partial epilepsy candidate for surgery underwent 3.0 T MR study after a 1.5 T MR study failed to disclose a relevant epileptogenic lesion. A potential lesion was found only in two patients (5.6%, 95% CI: 1.5-18.1%). Both were found to have hippocampal atrophy congruent with other presurgical localization techniques which resulted in omission of an invasive EEG study and direct passage to surgery. The frequency of detection of a new lesion by re-imaging at 3.0 T patients with refractory partial epilepsy candidate for surgery was found to be low, but seems to offer the potential of a significant clinical impact for selected patients. This finding needs to be validated in a prospective controlled study. Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Efficacy and tolerability of lacosamide as an adjunctive therapy in children with refractory partial epilepsy.

PubMed

Pasha, Ismail; Kamate, Mahesh; Didagi, Suresh K

2014-10-01

A unicentre, prospective study was performed to investigate the efficacy of lacosamide as adjunctive therapy in children with refractory partial epilepsy. The study was performed at a tertiary care hospital over a period of 30 months between November 2011 and May 2014. Seventy-nine children with refractory partial epilepsy (age 5-15 years) who had failed two or more antiepileptic drugs and in whom lacosamide was used as an add-on drug were enrolled. Lacosamide tablets were administered orally, at a dose of 25 mg for 1 week followed by 50 mg twice daily for the remaining period. Efficacy and tolerability evaluation was performed at every visit of titration, maintenance period (3 months), and two follow-up visits at monthly interval. Electrocardiogram and liver function tests were performed before enrollment and at the end of 3 months of lacosamide therapy. Patient's caregiver or investigator observed adverse events were recorded in a predesigned pro forma. A total of 79 patients with uncontrolled partial epilepsy screened from 531 epileptic children were enrolled, after they satisfied the inclusion and exclusion criteria. The mean age of children enrolled was 8.8 ± 3.1 years (range 5-15 years); 53 children (67.0%) were boys. Mean weight of the patients was 24.2 ± 9.8 kg. The mean age at the onset of seizures was 6.4 ± 3.5 years. The mean dose of lacosamide administered was 4.1 mg/kg. Three patients (3.8%) dropped out of the study, because of vomiting, aggressive behavior, and poor response, respectively. Of 76 patients (96.2%) entering the maintenance period, 35 patients (44.3%) were seizure free, 32 patients (40.6%) indicated ≥50% reduction in seizure frequency, 3 patients (3.8%) indicated 25-49% seizure reduction, and 9 patients (11.4%) either had no change in seizure frequency or experience increase in seizure frequency. Lacosamide is an effective add-on antiepileptic drug for children with refractory partial epilepsy and is well tolerated. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Efficacy of abatacept in systemic lupus erythematosus: a retrospective analysis of 11 patients with refractory disease.

PubMed

Danion, F; Rosine, N; Belkhir, R; Gottenberg, J E; Hachulla, E; Chatelus, E; Pugnet, G; Pers, Y M; Mariette, X; Sibilia, J; Seror, R

2016-11-01

Objective The objective of this study was to assess the safety and efficacy of abatacept in patients with SLE refractory to conventional treatment in routine clinical practice. Methods This retrospective study included 11 SLE patients treated with abatacept for an active and refractory disease. The primary endpoint was the change in SLE Disease Activity Index (SLEDAI) score at six months. Response was defined as a decrease of SLEDAI ≥4 in a patient continuing abatacept. Results Indications of abatacept treatment were articular ( n=8), renal ( n=1) and cutaneous ( n=1) involvement and autoimmune thrombocytopenia ( n=1). Abatacept was discontinued before six months in two patients, because of adverse event ( n=1) and/or lupus flare ( n=2). The median SLEDAI decreased from 6 (2-20) to 4 (0-20) ( p=0.031). Decrease of SLEDAI ≥4 was observed in 6/11 patients (55%) and response to treatment according to the physician's judgement in 8/11 (73%) patients. Improvement of articular involvement was observed in 7/8 (87.5%) patients. Four adverse events were observed in three patients, but no severe infection occurred. Conclusion This study suggests some efficacy of abatacept in patients with refractory disease in routine clinical practice, particularly in the case of articular manifestations, with an acceptable safety profile. These data support conducting new controlled trials of abatacept in SLE patients.

Mitigating the effects of in-vehicle distractions through use of the Psychological Refractory Period paradigm.

PubMed

Hibberd, Daryl L; Jamson, Samantha L; Carsten, Oliver M J

2013-01-01

Modern driving involves frequent and potentially detrimental interactions with distracting in-vehicle tasks. Distraction has been shown to slow brake reaction time and decrease lateral and longitudinal vehicle control. It is likely that these negative effects will become more prevalent in the future as advances are made in the functionality, availability, and number of in-vehicle systems. This paper addresses this problem by considering ways to manage in-vehicle task presentation to mitigate their distracting effects. A driving simulator experiment using 48 participants was performed to investigate the existence of the Psychological Refractory Period in the driving context and its effect on braking performance. Drivers were exposed to lead vehicle braking events in isolation (single-task) and with a preceding surrogate in-vehicle task (dual-task). In dual-task scenarios, the time interval between the in-vehicle and braking tasks was manipulated. Brake reaction time increased when drivers were distracted. The in-vehicle task interfered with the performance of the braking task in a manner that was dependent on the interval between the two tasks, with slower reactions following a shorter inter-task interval. This is the Psychological Refractory Period effect. These results have implications for driver safety during in-vehicle distraction. The findings are used to develop recommendations regarding the timing of in-vehicle task presentation so as to reduce their potentially damaging effects on braking performance. In future, these guidelines could be incorporated into a driver workload management system to minimise the opportunity for a driver to be distracted from the ongoing driving task. Copyright © 2012 Elsevier Ltd. All rights reserved.

Deep brain stimulation for the obsessive-compulsive and Tourette-like symptoms of Kleefstra syndrome.

PubMed

Segar, David J; Chodakiewitz, Yosef G; Torabi, Radmehr; Cosgrove, G Rees

2015-06-01

Deep brain stimulation (DBS) has been reported to have beneficial effects in severe, treatment-refractory cases of obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). In this report, the authors present the first case in which DBS was used to treat the neuropsychiatric symptoms of Kleefstra syndrome, a rare genetic disorder characterized by childhood hypotonia, intellectual disability, distinctive facial features, and myriad psychiatric and behavioral disturbances. A 24-year-old female patient with childhood hypotonia, developmental delay, and diagnoses of autism spectrum disorder, OCD, and TS refractory to medical management underwent the placement of bilateral ventral capsule/ventral striatum (VC/VS) DBS leads, with clinical improvement. Medical providers and family observed gradual and progressive improvement in the patient's compulsive behaviors, coprolalia, speech, and social interaction. Symptoms recurred when both DBS electrodes failed because of lead fracture and dislodgement, although the clinical benefits were restored by lead replacement. The symptomatic and functional improvements observed in this case of VC/VS DBS for Kleefstra syndrome suggest a novel indication for DBS worthy of further investigation.

An intravenous microdose of bevacizumab for the treatment of pigment epithelial detachment associated to age-related macular degeneration refractory to intravitreal bevacizumab: a case report.

PubMed

Wu, Lihteh; Evans, Teodoro

2011-01-01

The purpose of this study was to report the visual and anatomical outcomes of an intravenous microdose of 10 mg of bevacizumab in a patient with a vascularized pigment epithelial detachment (PED) associated with exudative age-related macular degeneration refractory to several intravitreal bevacizumab injections. Interventional case report and literature review. A 62-year-old female patient with a PED secondary to age-related macular degeneration was treated with 9 consecutive intravitreal injections of 2.5 mg of bevacizumab. Despite an initial response where the PED decreased in size, the subretinal fluid reabsorbed and the visual acuity improved; after the seventh injection, the PED started to grow in size again causing a drop in visual acuity. After an intravenous injection of 10 mg of bevacizumab, the patient experienced an improvement in visual acuity and a flattening of her PED. An intravenous injection of a microdose of bevacizumab appears to have resolved the PED with a sustained improvement of visual acuity.

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 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.

EPIC Computational Models of Psychological Refractory-Period Effects in Human Multiple-Task Performance.

ERIC Educational Resources Information Center

Meyer, David E.; Kieras, David E.

Perceptual-motor and cognitive processes whereby people perform multiple concurrent tasks have been studied through an overlapping-tasks procedure in which two successive choice-reaction tasks are performed with a variable interval (stimulus onset asynchrony, or SOA) between the beginning of the first and second tasks. The increase in subjects'…

Ir-based refractory superalloys by pulse electric current sintering (PECS) process (II prealloyed powder)

NASA Astrophysics Data System (ADS)

Huang, C.; Yamabe-Mitarai, Y.; Harada, H.

2002-02-01

Five prealloyed powder samples prepared from binary Ir-based refractory superalloys were sintered at 1800 °C for 4 h by Pulse Electric Current Sintering (PECS). No metal loss was observed during sintering. The relative densities of the sintered specimens all exceeded 90% T.D. The best one was Ir-13% Hf with the density of 97.82% T.D. Phases detected in sintered samples were in accordance with the phase diagram as expected. Fractured surfaces were observed in two samples (Ir-13% Hf and Ir-15% Zr). Some improvements obtained by using prealloyed powders instead of elemental powders, which were investigated in the previous studies, were presented.

Electro Processing Research

NASA Technical Reports Server (NTRS)

1982-01-01

Electroprocessing which is concerned with fluid dynamics of the electroreduction process to determine how it may be modified to improve the quality of the deposit was studied. Experimental techniques are used in this research. These techniques include laser Schlieren photography, laser Doppler velocimetry, and frequency spectrum analysis. Projects involve fluid flow studies of zinc plating in aqueous and molten salt electrolytes, study of cell design for magnesium chlorides electrolysis, digital signal analysis of manganese electrodeposition in molten chlorides, and electroplating of molybdenum from low melting salts. It is anticipated that the use of refractory metals as constructed materials in engineering will increase. Their electrodeposition from molten salt electrolytes is important in the extraction metallurgy of refractory metals.

The Management of Refractory Dry Eye With Semi-Scleral Contact Lens.

PubMed

Yuksel, Erdem; Bilgihan, Kamil; Novruzlu, Şahin; Yuksel, Nilay; Koksal, Murat

2018-05-01

We presented a case of refractory dry eye management with semi-scleral contact lens. Dry eye was associated with facial nerve (cranial nerve VII) palsy as a result of cerebellopontine angle tumor surgery. She was treated with several topical treatments and punctal plug. Despite the treatments, her symptoms still persisted. Her ophthalmic examination revealed scleral exposure because of lagophthalmos, conjunctival hyperemia, corneal debris, scar, and diffuse punctate epitheliopathy on her right eye. Lissamine green staining showed diffuse conjunctival and corneal staining. Therapeutic semi-scleral lenses were fitted. The corneal findings were resolved and the quality of patient life was improved with the aid of semi-scleral lens after 3 months.

Good Outcomes with the Intraventricular Vancomycin Therapy in a Patient with Ruptured Brain Abscesses

PubMed Central

Doan, Ninh; Nguyen, Ha; Luyuan, Li; Shabani, Saman; Gelsomino, Michael; Johnson, Vijay

2018-01-01

Brain abscesses are associated with high morbidity and mortality rates. In particular, patients with intraventricular rupture of brain abscess (IVROBA) exhibit mortality rates up to 85%. Treatment options are lacking for IVROBA, once patients become refractory to intravenous antibiotics and surgical drainage. Limited data exist regarding the risks and benefits of intraventricular therapy in such a scenario. We report a patient with IVROBA, who deteriorated while on systemic antibiotics; once intraventricular vancomycin was employed, the patient demonstrated remarkable improvement without perceivable side effects. This case suggests that intraventricular vancomycin may be a safe, effective, and viable option for the treatment of IVROBA, especially for patients becoming refractory to systemic antibiotics. PMID:29682042

Uveitis in children.

PubMed

Angeles-Han, Sheila T; Rabinovich, Consuelo Egla

2016-09-01

The review provides updates on novel risk markers for the development of pediatric inflammatory uveitis and a severe disease course, on treatment of refractory disease, and on the measurement of visual outcomes. There are several new genetic markers, biomarkers, and clinical factors that may influence a child's uveitis disease course. It is important to identify children at risk for poor visual outcomes and who are refractory to traditional therapy. Racial disparities have recently been reported. We describe agents of potential benefit. In addition, we discuss the importance of patient reported outcomes in this population. Uveitis can lead to vision-threatening complications. Timely and aggressive treatment of children identified to be at risk for a severe uveitis course may lead to improved outcomes.

Improving neuromodulation technique for refractory voiding dysfunctions: two-stage implant.

PubMed

Janknegt, R A; Weil, E H; Eerdmans, P H

1997-03-01

Neuromodulation is a new technique that uses electrical stimulation of the sacral nerves for patients with refractory urinary urge/frequency or urge-incontinence, and some forms of urinary retention. The limiting factor for receiving an implant is often a failure of the percutaneous nerve evaluation (PNE) test. Present publications mention only about a 50% success score for PNE of all patients, although the micturition diaries and urodynamic parameters are similar. We wanted to investigate whether PNE results improved by using a permanent electrode as a PNE test. This would show that improvement of the PNE technique is feasible. In 10 patients where the original PNE had failed to improve the micturition diary parameters more than 50%, a permanent electrode was implanted by operation. It was connected to an external stimulator. In those cases where the patients improved according to their micturition diary by more than 50% during a period of 4 days, the external stimulator was replaced by a permanent subcutaneous neurostimulator. Eight of the 10 patients had a good to very good result (60% to 90% improvement) during the testing period and received their implant 5 to 14 days after the first stage. The good results of the two-stage implant technique we used indicate that the development of better PNE electrodes may lead to an improvement of the testing technique and better selection between nonresponders and technical failures.

Combined ω3 and ω6 supplementation in children with attention-deficit hyperactivity disorder (ADHD) refractory to methylphenidate treatment: a double-blind, placebo-controlled study.

PubMed

Perera, Hemamali; Jeewandara, Kamal Chandima; Seneviratne, Sudarshi; Guruge, Chandima

2012-06-01

Children (6-12 years) with attention-deficit hyperactivity disorder (ADHD) being treated with methylphenidate and standard behavior therapy for more than 6 months, whose parents reported no improvement in behavior and academic learning, were randomly assigned to receive supplementation with a combined ω3 and ω6 preparation or a placebo. Outcome was measured at 3 and 6 months after treatment using a self-assessment checklist completed by the parents. Statistically significant improvement was found in the treatment group compared with the placebo group (P < .01) in the following measures: restlessness, aggressiveness, completing work, and academic performance. Statistically significant improvement was not found at 3 months of treatment between groups but was evident at 6 months of treatment (P < .05) with inattention, impulsiveness, and cooperation with parents and teachers. Distractibility failed to show improvement. Effect sizes ranged from 0.3 to 1.1 at 3 months and 0.2 to 1.4 at 6 months for individual symptom variables.

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.

Compatibility of Niobium Alloys and Superalloys in a Flowing He-Xe Power Conversion System

NASA Technical Reports Server (NTRS)

Bowman, Cheryl L.; Ritzert, Frank J.; Smialek, James L.; Jaster, Mark L.; rker, Samuel P.

2004-01-01

Proposed concepts for an ambitious mission to explore Jupiter's three icy moons place significant demands on the various spacecraft systems. There are many challenges related to the high output power conversion systems being considered, and one example is the need to ensure system compatibility at all levels. The utilization of appropriate materials for component structures is important to ensuring long mission life. Refractory metal alloys have attractive high-temperature properties in inert environments, but these alloys are sometimes susceptible to contamination. Potential material compatibility issues exist between refractory metal candidates and more conventional alloys. Nb-1Zr has long been considered one of the most well characterized refractory alloys that is well suited for elevated-temperature use and liquid-metal compatibility. However, previous studies have suggested that niobium alloys can not co-exist in a closed system with traditional stainless steels or superalloys due to transport of contaminants. The relevance of this information to a proposed power conversion system is discussed. Also, experiments and fundamental calculations are being performed to determine contamination transport from candidate superalloys to Nb-1Zr in a closed system with an inert carrier gas. Potential protective schemes are explored to ensure system level compatibility between the refractory alloy Nb-1Zr and a nickel-based superalloy.

Nanostructured refractory thin films for solar applications

NASA Astrophysics Data System (ADS)

Ollier, E.; Dunoyer, N.; Dellea, O.; Szambolics, H.

2014-08-01

Selective solar absorbers are key elements of all solar thermal systems. Solar thermal panels and Concentrated Solar Power (CSP) systems aim respectively at producing heat and electricity. In both cases, a surface receives the solar radiation and is designed to have the highest optical absorption (lowest optical reflectivity) of the solar radiation in the visible wavelength range where the solar intensity is the highest. It also has a low emissivity in the infrared (IR) range in order to avoid radiative thermal losses. Current solutions in the state of the art usually consist in deposited interferential thin films or in cermets [1]. Structured surfaces have been proposed and have been simulated because they are supposed to be more efficient when the solar radiation is not normal to the receiving surface and because they could potentially be fabricated with refractory materials able to sustain high operating temperatures. This work presents a new method to fabricate micro/nanostructured surfaces on molybdenum (refractory metal with a melting temperature of 2623°C). This method now allows obtaining a refractory selective surface with an excellent optical selectivity and a very high absorption in the visible range. This high absorption performance was obtained by achieving a double structuration at micro and nano scales thanks to an innovative process flow.

[Prevalence of target organ damage and factors associated with cardiovascular events in subjects with refractory hypertension].

PubMed

Armario, Pedro; Oliveras, Anna; Hernández Del Rey, Raquel; Poch, Esteban; Larrouse, María; Roca-Cusachs, Alex; de la Sierra, Alejandro

2009-06-27

To asses the prevalence of target organ damage (TOD) and factors associated with cardiovascular events in subjects with refractory hypertension. Cross-sectional study of 146 patients with clinical diagnosis of refractory hypertension. TOD was defined as the presence of microalbuminuria (MA), renal failure (RF), left ventricular hypertrophy (LVH) or left atrial enlargement (LAE). Cardiovascular events were defined as the antecedent of stroke, coronary heart disease, heart failure or peripheral arterial disease. 24-h ambulatory blood pressure monitoring was (ABPM) performed with a validated Spacelabs 90207. The prevalence of LVH was 62.3%, and LAE was observed in 27.7% of the subjects. The prevalence of RF was 28.1% and MA was found in 41,4%. An association between MA and LVH was observed. After adjusting by age, the urinary albumin excretion (UAE) correlated with clinical blood pressure (BP) and BP during 24-h ABPM, whereas LVMI correlated with ambulatory BP but not with clinical BP. The prevalence of previous cardiovascular events was 22% and in the multivariate regression analysis, UAE was the only independent factor associated with the antecedent of cardiovascular events. In subjects with refractory hypertension, the prevalence of TOD was high, and an association between heart and renal organ damage was observed. UAE was independently associated with the antecedent of cardiovascular disease.

Pharmacologic therapies for severe steroid refractory hospitalized ulcerative colitis: A network meta-analysis.

PubMed

Komaki, Yuga; Komaki, Fukiko; Micic, Dejan; Yamada, Akihiro; Suzuki, Yasuo; Sakuraba, Atsushi

2017-06-01

A limited option of therapies is available for hospitalized patients with severe steroid refractory ulcerative colitis (UC). Furthermore, there exists a paucity of direct comparisons between them. To provide a comparative evaluation of the efficacy and safety of pharmacologic therapies, we conducted a network meta-analysis combined with a benefit-risk analysis of randomized controlled trials (RCTs) performed in hospitalized patients with severe steroid refractory UC. Electronic databases were searched through November 2015 for RCTs evaluating the efficacy of therapies for severe steroid refractory hospitalized UC. The outcomes were clinical response, colectomy free rate, and severe adverse events leading to discontinuation of therapy. The primary endpoints were the rank of therapies based on network meta-analysis combined with benefit-risk analysis between clinical response and severe adverse events as well as colectomy free rate and severe adverse events. Eight RCTs of 421 patients were identified. Cyclosporine, infliximab, and tacrolimus as well as placebo were included in our analysis. Network meta-analysis with benefit-risk analysis simultaneously assessing clinical response and severe adverse events demonstrated the rank order of efficacy as infliximab, cyclosporine, tacrolimus, and placebo. Similar analysis for colectomy-free rate and severe adverse events demonstrated the same rank order of efficacy. The differences among infliximab, cyclosporine, and tacrolimus were small in all analyses. The results of the present comprehensive benefit-risk assessment using network meta-analysis provide RCT-based evidence on efficacy and safety of infliximab, cyclosporine, and tacrolimus for hospitalized patients with severe steroid refractory UC. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Next generation internet architecture and cyber-assisted energy efficiency in smart grids of buildings

NASA Astrophysics Data System (ADS)

Peterson, Robb Alex

Northern Minnesota's iron mines are the starting point for the majority of the steel that gets produced in the United States. Their taconite processing plants use heat in furnaces to oxidize and indurate iron in the final stage of making a taconite pellet. Facilities can increase efficiencies when refractory service life is maintained. Efficiencies gained include: less fuel used, better quality control, better furnace control, and less mechanical component maintenance. Furnace refractory linings fail when the cracks that develop in them are uncontrolled or too large. These failures allow heat and gases retained by the lining to reach structural or mechanical components. Furnace control and efficiencies are also compromised when heat and gases are allowed to short circuit or escape the system. These failures are primarily the result of thermal of shock and expansion. It is common place to add stainless steel needle reinforcement to a monolithic refractory in an effort to counteract these effects. This study used several standard ASTM testing procedures to test 65% alumina mullite based refractory samples with 304 and 406 grade stainless steel needles. Mechanical property data gathered was used to analyze performance. The study found that adding reinforcement does not increase initial Compression and Cold Modulus of Ruptures strengths, however, after prolonged heat and thermal shock exposure, needles help maintain integrity and mechanical properties of samples. The study also found that corrosion due to oxidation was a major contributing factor to the way needles performed; and concluded that a concentration of 3% 406 "Alfa 1" stainless steel reinforcing needles added to the working lining of a taconite furnace is recommended.

The use of selective serotonin receptor inhibitors (SSRIs) is not associated with increased risk of endoscopy-refractory bleeding, rebleeding or mortality in peptic ulcer bleeding.

PubMed

Laursen, S B; Leontiadis, G I; Stanley, A J; Hallas, J; Schaffalitzky de Muckadell, O B

2017-08-01

Observational studies have consistently shown an increased risk of upper gastrointestinal bleeding in users of selective serotonin receptor inhibitors (SSRIs), probably explained by their inhibition of platelet aggregation. Therefore, treatment with SSRIs is often temporarily withheld in patients with peptic ulcer bleeding. However, abrupt discontinuation of SSRIs is associated with development of withdrawal symptoms in one-third of patients. Further data are needed to clarify whether treatment with SSRIs is associated with poor outcomes, which would support temporary discontinuation of treatment. To identify if treatment with SSRIs is associated with increased risk of: (1) endoscopy-refractory bleeding, (2) rebleeding or (3) 30-day mortality due to peptic ulcer bleeding. A nationwide cohort study. Analyses were performed on prospectively collected data on consecutive patients admitted to hospital with peptic ulcer bleeding in Denmark in the period 2006-2014. Logistic regression analyses were used to investigate the association between treatment with SSRIs and outcome following adjustment for pre-defined confounders. Sensitivity and subgroup analyses were performed to evaluate the validity of the findings. A total of 14 343 patients were included. Following adjustment, treatment with SSRIs was not associated with increased risk of endoscopy-refractory bleeding (odds ratio [OR] [95% Confidence Interval (CI)]: 1.03 [0.79-1.33]), rebleeding (OR [95% CI]: 0.96 [0.83-1.11]) or 30-day mortality (OR [95% CI]: 1.01 [0.85-1.19]. These findings were supported by sensitivity and subgroup analyses. According to our data, treatment with SSRIs does not influence the risk of endoscopy-refractory bleeding, rebleeding or 30-day mortality in peptic ulcer bleeding. © 2017 John Wiley & Sons Ltd.

The effects of topical aqueous sirolimus on tear production in normal dogs and dogs with refractory dry eye.

PubMed

Spatola, Ronald; Nadelstein, Brad; Berdoulay, Andrew; English, Robert V

2018-05-01

To evaluate the effect of twice daily aqueous 0.02% sirolimus drops on tear production in normal dogs and dogs with refractory keratoconjunctivitis sicca (KCS). Two groups of dogs were studied. Ten normal dogs with no signs of ocular disease were administered topical 0.02% sirolimus ophthalmic solution in right eye, and a vehicle control in the left eye twice daily for 4 weeks. Complete ophthalmic examinations, including Schirmer tear test were performed weekly. Eighteen dogs with refractory KCS were randomly assigned to receive 0.02% sirolumus ophthalmic solution or 0.02% tacrolimus ophthalmic solution twice daily. Complete ophthalmic examinations were was performed at 2 and 6 weeks following treatment. Tear production in the sirolimus-treated eyes of normal dogs was greater when compared to vehicle controls with a mean difference over all time points of 3.46 mm (95% CI 1.17, 5.75; P = 0.006). After 4 weeks of treatment, the mean difference was 5 mm (95% CI 1.95, 8.05; P = 0.002). In dogs with refractory dry eye, 37.5% of eyes treated with sirolimus exhibited increased tear production >4 mm/min after 6 weeks of treatment, compared to 20% of eyes receiving tacrolimus (P = 0.433). One normal dog experienced topical irritation to both sirolimus and vehicle-treatment. Side effects were not reported in any treated eyes with chronic KCS. Topical 0.02% sirolimus might be an alternative treatment for canine patients with keratoconjunctivits sicca. The drug appears safe when applied topically in an aqueous suspension for up to 6 weeks. While initial results are promising, further studies are warranted. © 2017 American College of Veterinary Ophthalmologists.

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.

Solar Thermal Propulsion Improvements at Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

Gerrish, Harold P.

2003-01-01

Solar Thermal Propulsion (STP) is a concept which operates by transferring solar energy to a propellant, which thermally expands through a nozzle. The specific impulse performance is about twice that of chemical combustions engines, since there is no need for an oxidizer. In orbit, an inflatable concentrator mirror captures sunlight and focuses it inside an engine absorber cavity/heat exchanger, which then heats the propellant. The primary application of STP is with upperstages taking payloads from low earth orbit to geosynchronous earth orbit or earth escape velocities. STP engines are made of high temperature materials since heat exchanger operation requires temperatures greater than 2500K. Refractory metals such as tungsten and rhenium have been examined. The materials must also be compatible with hot hydrogen propellant. MSFC has three different engine designs, made of different refractory metal materials ready to test. Future engines will be made of high temperature carbide materials, which can withstand temperatures greater than 3000K, hot hydrogen, and provide higher performance. A specific impulse greater than 1000 seconds greatly reduces the amount of required propellant. A special 1 OkW solar ground test facility was made at MSFC to test various STP engine designs. The heliostat mirror, with dual-axis gear drive, tracks and reflects sunlight to the 18 ft. diameter concentrator mirror. The concentrator then focuses sunlight through a vacuum chamber window to a small focal point inside the STP engine. The facility closely simulates how the STP engine would function in orbit. The flux intensity at the focal point is equivalent to the intensity at a distance of 7 solar radii from the sun.

Neuroimaging evaluation in refractory epilepsy

PubMed Central

Granados, Ana M; Orejuela, Juan F

2015-01-01

Purpose To describe the application of neuroimaging analysis, compared to neuropsychological tests and video-electroencephalogram, for the evaluation of refractory epilepsy in a reference centre in Cali, Colombia. Methods Between March 2013 and November 2014, 29 patients, 19 men and 10 women, aged 9–65 years and with refractory epilepsy, were assessed by structural and functional magnetic resonance imaging while performing tasks related to language, verbal and non-verbal memory. Also, volumetric evaluation was performed. A 1.5 Tesla magnetic resonance imaging scanner was used in all cases. Results Neuroimaging evaluation identified 13 patients with mesial temporal sclerosis. The remaining patients were classified as: 10 patients with neoplastic masses, two patients with cortical atrophy, two patients with scarring lesions and two patients with non-structural aetiology. Among patients with mesial temporal sclerosis, comparison between techniques for lateralising the epileptogenic foci was made; the κ index between functional magnetic resonance imaging and hippocampi volumetry was κ = 1.00, agreement between neuroimaging and video-electroencephalogram was good (κ = 0.78) and comparison with a neuropsychological test was mild (κ = 0.24). Conclusions Neuroimaging studies allow the assessment of functional and structural damage related to epileptogenic lesions and foci, and are helpful to select surgical treatment, conduct intraoperative neuronavigation techniques, predict surgical deficits and evaluate patient recovery. PMID:26427897

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

Long-term salvage therapy with cyclosporin A in refractory idiopathic thrombocytopenic purpura.

PubMed

Emilia, Giovanni; Morselli, Monica; Luppi, Mario; Longo, Giuseppe; Marasca, Roberto; Gandini, Giovanna; Ferrara, Leonardo; D'Apollo, Nicola; Potenza, Leonardo; Bertesi, Marcello; Torelli, Giuseppe

2002-02-15

Treatment of severe, chronic idiopathic thrombocytopenic purpura (ITP) refractory to most usual therapies is a difficult challenge. Little information exists on the clinical use of cyclosporin A (CyA) in the treatment of ITP. This report describes long-term treatment with CyA (median, 40 months) and follow-up (median, 36.8 months) in 12 adult patients with resistant ITP. CyA used in relatively low doses (2.5-3 mg/kg of body weight per day) led to a clinical improvement in 10 patients (83.3%). Five had a complete response (41.1%), 4 a complete response to maintenance therapy (33.3%), and one a partial response (8.3%). Two patients had no response. Most patients with a response (60%) had a long-term remission (mean, 28.6 months) after discontinuation of CyA. One patient had a relapse of ITP 4 years after CyA therapy was stopped. Side effects were moderate and transient, even in patients dependent on continued CyA treatment. CyA seems to represent reasonable salvage treatment in severe, potentially life-threatening, refractory ITP.

Alemtuzumab as treatment of steroid-refractory acute graft-versus-host disease: results of a phase II study.

PubMed

Martínez, Carmen; Solano, Carlos; Ferrá, Christelle; Sampol, Antonia; Valcárcel, David; Pérez-Simón, José Antonio

2009-05-01

We conducted a phase II trial to investigate the safety and efficacy of alemtuzumab in treating steroid-refractory acute graft-versus-host disease (aGVHD) grade II or higher after stem cell transplantation. Ten adult patients (6 with aGVHD grade III and 4 with aGVHD grade IV) were included in the study. Nine patients had gastrointestinal tract involvement, 7 had skin involvement, and 5 had liver involvement. Five patients responded to treatment, 2 with complete response and 3 with partial response. Eight infectious events (4 of grade 3-4) and 7 cytomegalovirus (CMV) reactivations were observed. Six patients had grade 3-4 cytopenia. All 10 patients died (7 resulting from aGVHD progression, 2 from severe infection, and 1 from to leukemia relapse), at a median of 40 days (range, 4 to 88 days) after alemtuzumab treatment. Overall, our findings suggest that steroid-refractory aGVHD may be improved by treatment with alemtuzumab, but that this treatment does not overcome the dismal prognosis of patients with severe aGVHD, demonstrating the need for alternative therapies to treat this complication.

Successful treatment of generalized refractory chronic periodontitis through discontinuation of waxed or coated dental floss use: A report of 4 cases.

PubMed

Kelekis-Cholakis, Anastasia; Perry, John B; Pfeffer, Lorraine; Millete, Amy

2016-12-01

Generalized refractory chronic periodontitis is a periodontal condition that is resistant to conventional therapy. Management of this condition often is frustrating to both the patient and the clinician. The authors present 4 cases of generalized refractory chronic periodontitis characterized by an inflammatory gingival response and progressive bone loss that did not respond to extensive periodontal treatments and regular periodontal care. Histologic examination of affected gingival tissue revealed an abundance of plasma cells, a feature seen in certain oral contact hypersensitivity reactions. The authors suspected that waxed or coated dental floss was the offending contactant, and its removal from the patients' oral hygiene regimens resulted in a dramatic improvement of the periodontal characteristics. In cases of periodontal disease as described in this report, dental practitioners should consider the possibility of a contact hypersensitivity reaction to waxed or coated dental floss, whereby the floss exacerbates the condition instead of assisting in its resolution. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

Better VPS Fabrication of Crucibles and Furnace Cartridges

NASA Technical Reports Server (NTRS)

Holmes, Richard R.; Zimmerman, Frank R.; O'Dell, J. Scott; McKechnie, Timothy N.

2003-01-01

An experimental investigation has shown that by (1) vacuum plasma spraying (VPS) of suitable refractory metal alloys on graphite mandrels, and then (2) heat-treating the VPS alloy deposits under suitable conditions, it is possible to fabricate improved crucibles and furnace cartridges that could be used at maximum temperatures between 1,400 and 1,600 C and that could withstand chemical attack by the materials to be heated in the crucibles and cartridges. Taken by itself, the basic concept of fabricating furnace cartridges by VPS of refractory materials onto graphite mandrels is not new; taken by itself, the basic concept of heat treatment of VPS deposits for use as other than furnace cartridges is also not new; however, prior to this investigation, experimental crucibles and furnace cartridges fabricated by VPS had not been heat treated and had been found to be relatively weak and brittle. Accordingly, the investigation was directed toward determining whether certain combinations of (1) refractory alloy compositions, (2) VPS parameters, and (3) heat-treatment parameters could result in VPS-fabricated components with increased ductility.

Electroconvulsive therapy for medication-refractory depression in a patient with ruptured intracranial dermoid cyst, meningioma, and neurofibromatosis.

PubMed

Thukral-Mahajan, Priyanka; Shah, Nilesh; Kalra, Gurvinder; Andrade, Chittaranjan

2017-01-01

Electroconvulsive therapy (ECT) is considered relatively contraindicated in patients with intracranial space-occupying lesions. A 53-year-old male presented with a 5-year history of medication-refractory major depressive disorder. Brain imaging findings suggested the presence of a ruptured dermoid cyst in the transverse sinus and a calcified meningioma in the temporal lobe sulcal space. There was no evidence of mass effect. Neurofibromatosis was the only other clinical condition present. The patient had no clinical neurological deficits. Since the depression was severe and he was suicidal, ECT was advised. There was a substantial improvement after four bilateral and then eight right unilateral brief-pulse ECTs administered on alternate days, thrice weekly. There were no complications associated with ECT. The treatment gains were maintained with maintenance antidepressant medication at a 1-year follow-up. This is probably the first reported case of the use of ECT in a medication-refractory, severely depressed patient with a ruptured intracranial dermoid cyst and with a calcifying meningioma. The results testify to the safety of ECT even in high-risk patients.

Constraints on Galactic Cosmic-Ray Origins from Elemental Composition Measurements

NASA Astrophysics Data System (ADS)

Binns, W. R.; Christian, E. R.; Cummings, A. C.; Denolfo, G. A.; Israel, M. H.; Lave, K. A.; Leske, R. A.; Mewaldt, R. A.; Stone, E. C.; von Rosenvinge, T. T.; Wiedenbeck, M. E.

2017-01-01

We present measurements of the abundances of ultra-heavy (Z>29) cosmic rays made by the CRIS instrument on NASA's Advanced Composition Explorer satellite. The data set corresponds to 6413 days of data collection between December 4, 1997 and May 31, 2016. The charge resolution that we obtain is excellent, exhibiting essentially complete separation of adjacent charges in the Z>28 range. We detected 196 events over the charge range of Z =30-40. Our measured abundances show that the ordering of refractory and volatile elements with atomic mass is greatly improved when compared to a mix of massive star outflow and SN ejecta with normal ISM, rather than pure ISM. Additionally, the refractory and volatile elements have similar slopes and refractory elements are preferentially accelerated by a factor of 4. The measured abundances support a model in which 20% of cosmic ray source material is from massive star outflow and ejecta and 80% is from normal ISM. Our abundances show generally good agreement with the TIGER and SuperTIGER results. This research is supported by NASA under Grant # NNX13AH66G.

Partial clinical response to anakinra in severe palmoplantar pustular psoriasis.

PubMed

Tauber, M; Viguier, M; Alimova, E; Petit, A; Lioté, F; Smahi, A; Bachelez, H

2014-09-01

Palmoplantar pustular psoriasis is a clinical psoriasis variant characterised by a high impact on quality of life and poor response to biologics approved for plaque type psoriasis.The recombinant interleukin-1 (IL-1) receptor antagonist anakinra has been recently used for the treatment of isolated refractory cases of generalised pustular psoriasis with contrasted results. To report the clinical response in two patients treated with anakinra as salvage therapy in two patients with severe palmoplantar pustular psoriasis refractory to currently available antipsoriatic systemic therapies. Anakinra was given subcutaneously at the daily dose of 100 mg, and clinical response was evaluated using the palmoplantar psoriasis area and severity index (PPPASI). Only partial and transient responses were observed in both patients, who had to stop anakinra due to lack of efficacy and to side effects. Anakinra appears to provide only partial clinical improvement in refractory palmoplantar pustular psoriasis. Prospective clinical studies on larger populations are warranted to investigate more accurately both efficacy and safety of IL-1-inhibiting strategies in pustular psoriasis. © 2014 British Association of Dermatologists.

Improving the thermal and physical properties of fire clay refractory bricks by added magnesia

NASA Astrophysics Data System (ADS)

Ibrahim, Sarmad I.; Ali, Nahedh M.; Abood, Tamara W.

2018-05-01

In this study, the Local natural Iraqi rocks kaolin with the addition of different proportions of MgO along with its effects on the physical and thermal properties of the prepared refractories were investigated. kaolin/MgO mixture was milled and classified into various size fractions, the kaolin (less than 105 µm) and MgO (less than 50µm). The specimens were mixed from kaolin and MgO in range M1 (95+5)%, M2 (90+10) %, M3(85+15)% and M4(80+20)% respectively. The green specimens were shaped by the semi-dry method using a hydraulic press and a molding pressure of (5)Ton with addition of (9-12) %wt. of pva solution ratio. After molding and drying, the specimens were fired at (1100, 1200 and 1300)°C. Physical properties (density, porosity, Water Absorption) and thermal properties (thermal conductivity) were measured for all the prepared samples. The results showed that the porosity was increased and the density was decreased, such increase &decrease affected on to the thermal properties for refractory.

Refractory hepatic encephalopathy in a patient with hypothyroidism: Another element in ammonia metabolism

PubMed Central

Díaz-Fontenla, Fernando; Castillo-Pradillo, Marta; Díaz-Gómez, Arantxa; Ibañez-Samaniego, Luis; Gancedo, Pilar; Guzmán-de-Villoria, Juan Adan; Fernández-García, Pilar; Bañares-Cañizares, Rafael; García-Martínez, Rita

2017-01-01

Hepatic encephalopathy (HE) remains a diagnosis of exclusion due to the lack of specific signs and symptoms. Refractory HE is an uncommon but serious condition that requires the search of hidden precipitating events (i.e., portosystemic shunt) and alternative diagnosis. Hypothyroidism shares clinical manifestations with HE and is usually considered within the differential diagnosis of HE. Here, we describe a patient with refractory HE who presented a large portosystemic shunt and post-ablative hypothyroidism. Her cognitive impairment, hyperammonaemia, electroencephalograph alterations, impaired neuropsychological performance, and magnetic resonance imaging and spectroscopy disturbances were highly suggestive of HE, paralleled the course of hypothyroidism and normalized after thyroid hormone replacement. There was no need for intervention over the portosystemic shunt. The case findings support that hypothyroidism may precipitate HE in cirrhotic patients by inducing hyperammonaemia and/or enhancing ammonia brain toxicity. This case led us to consider hypothyroidism not only in the differential diagnosis but also as a precipitating factor of HE. PMID:28811719

Management of refractory pityriasis rubra pilaris: challenges and solutions

PubMed Central

Moretta, Gaia; De Luca, Erika V; Di Stefani, Alessandro

2017-01-01

Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory papulosquamous skin disease. Its clinical presentation and evolution is very variable. The most frequent clinical features are follicular papules, progressing to yellow-orange erythroderma with round small areas of normal skin and the well-demarcated palmoplantar keratoderma. Actually, six different types of PRP have been described based on clinical characteristics, age of onset, and prognosis. The pathogenesis is still unknown, and treatment can be challenging. Available treatments are mainly based on case reports or case series of clinical experience because no controlled randomized trials have never been performed because of the rarity of the condition. Traditional systemic treatment consists in retinoids, which are actually considered as first-line therapy, but refractory cases that do not respond or relapse after drug interruption do exist. In recent years, numerous reports have demonstrated the efficacy of new agents such as biological drugs. This article is an overview on available therapeutic options, in particular for refractory forms of PRP. PMID:29184428

Refractory Materials for Flame Deflector Protection

NASA Technical Reports Server (NTRS)

Calle, Luz M.; Hintze, Paul E.; Parlier, Christopher R.; Sampson, Jeffrey W.; Curran, Jerome P.; Kolody, Mark R.; Peruisich, Stephen A.

2010-01-01

Fondu Fyre (FF) is currently the only refractory material qualified for use in the flame trench at KSC's Shuttle Launch Pads 39A and 3913. However, the material is not used as it was qualified and has undergone increasingly frequent and severe degradation due to the launch blasts. This degradation is costly as well as dangerous for launch infrastructure, crew and vehicle. The launch environment at KSC is unique. The refractory material is subject to the normal seacoast environment, is completely saturated with water before launch, and is subjected to vibrations and aggressive heat/blast conditions during launch. This report presents results comparing two alternate materials, Ultra-Tek FS gun mix and Kruzite GR Plus, with Fondu Fyre. The materials were subjected to bulk density, porosity, compression strength, modulus of rupture and thermal shock tests. In addition, test specimens were exposed to conditions meant to simulate the launch environment at KSC to help better understand how the materials will perform once installed.

Refractory hepatic encephalopathy in a patient with hypothyroidism: Another element in ammonia metabolism.

PubMed

Díaz-Fontenla, Fernando; Castillo-Pradillo, Marta; Díaz-Gómez, Arantxa; Ibañez-Samaniego, Luis; Gancedo, Pilar; Guzmán-de-Villoria, Juan Adan; Fernández-García, Pilar; Bañares-Cañizares, Rafael; García-Martínez, Rita

2017-07-28

Hepatic encephalopathy (HE) remains a diagnosis of exclusion due to the lack of specific signs and symptoms. Refractory HE is an uncommon but serious condition that requires the search of hidden precipitating events ( i.e ., portosystemic shunt) and alternative diagnosis. Hypothyroidism shares clinical manifestations with HE and is usually considered within the differential diagnosis of HE. Here, we describe a patient with refractory HE who presented a large portosystemic shunt and post-ablative hypothyroidism. Her cognitive impairment, hyperammonaemia, electroencephalograph alterations, impaired neuropsychological performance, and magnetic resonance imaging and spectroscopy disturbances were highly suggestive of HE, paralleled the course of hypothyroidism and normalized after thyroid hormone replacement. There was no need for intervention over the portosystemic shunt. The case findings support that hypothyroidism may precipitate HE in cirrhotic patients by inducing hyperammonaemia and/or enhancing ammonia brain toxicity. This case led us to consider hypothyroidism not only in the differential diagnosis but also as a precipitating factor of HE.

Systematic Review With Meta-Analysis: Anti-TNF Therapy in Refractory Pouchitis and Crohn's Disease-Like Complications of the Pouch After Ileal Pouch-Anal Anastomosis Following Colectomy for Ulcerative Colitis.

PubMed

Huguet, Mathilde; Pereira, Bruno; Goutte, Marion; Goutorbe, Félix; Dubois, Anne; Bommelaer, Gilles; Buisson, Anthony

2018-01-18

Inflammatory complications including chronic refractory pouchitis and Crohn's disease (CD)-like complications of the pouch are common complications after ileal pouch-anal anastomosis (IPAA) following colectomy for ulcerative colitis (UC). We performed a systematic review and meta-analysis to evaluate the efficacy of anti-TNF therapy in distinguishing patients with chronic refractory pouchitis from those with CD-like complications of the pouch. We performed a systematic literature search to identify articles and abstracts reporting anti-TNF agents efficacy in treating inflammatory complications of the pouch after IPAA for UC. Short-term and long-term remissions were evaluated at 8 weeks 95%CI[5-10] and 12 months 95%CI[12-18.5], respectively. We identified 21 articles and 3 abstracts including 313 patients treated either with infliximab (n = 194) or adalimumab (n = 119) for inflammatory complications of the pouch. The rates of short-term and long-term clinical remission were 0.50 (95%CI [0.37-0.63]; I2 = 0.57) and 0.52 (95%CI[0.39-0.65]; I2 = 0.59), respectively. The rate of remission after anti-TNF induction therapy seemed to be higher in CD-like complications of the pouch 0.64 (95%CI[0.5-0.77]; I2 = 0.18), compared to refractory pouchitis 0.10 (95%CI [0.00-0.35]; I2 = 0.00) (P = 0.06), whereas no such difference appeared after long-term maintenance therapy 0.57 (95%CI[0.43-0.71]; I2 = 0.32) and 0.37 (95%CI [0.14-0.62]; I2 = 0.47), respectively (P = 0.57). Sensitivity analyses suggested no difference in outcomes. No significant publication bias has been detected. Anti-TNF agents have a clear trend to have higher and faster efficacy in CD-like complications of the pouch compared to refractory pouchitis, highlighting the need to differentiate these two entities both in daily practice and clinical trials. © 2018 Crohn’s & Colitis Foundation of America. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

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

Case series of 17 modified Weil's osteotomies for Freiberg's and Köhler's II AVN, with AOFAS scoring pre- and post-operatively.

PubMed

Edmondson, M C; Sherry, K R; Afolayan, J; Armitage, A R; Skyrme, A D

2011-03-01

Treatment for metatarsal head avascular necrosis is largely conservative. For severe or refractory cases there are various surgical options. We have performed a 'modified Weil's osteotomy' of the distal metatarsal in order to manage this problem. We present the largest case series, to our knowledge, with 17 such cases. The patients were scored pre- and post-operatively using the AOFAS Forefoot scoring system. We found that this procedure provided a mean score improvement of 36 points, with a complication rate of 5.9%. We would advocate this modified osteotomy as an effective, reliable and safe treatment option. Copyright © 2009 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

TAS-102: a novel antimetabolite for the 21st century

PubMed Central

Uboha, Nataliya; Hochster, Howard S

2016-01-01

TAS-102, a novel antimetabolite combination chemotherapy agent, consists of a rediscovered antimetabolite agent, trifluorothymidine (trifluridine) combined with the metabolic inhibitor of thymidine phosphorylase, tipiracil, in a 1:0.5 molar ratio. Mechanism of action studies suggest that this agent works by incorporation into DNA. Both preclinical and clinical studies demonstrate that this agent is noncross-resistant with 5-fluorouracil. Tipiracil may also have antiangiogenic effects through inhibition of thymidine phosphorylase. Recent randomized Phase II and III trials demonstrate clinical activity (improved progression-free survival, time to decrease in performance status, prolonged overall survival) in metastatic colorectal cancer refractory to all standard agents. Monotherapy with TAS-102 has now been approved for this indication in Japan and in the USA. PMID:26616466

Use of methylphenidate in the treatment of patients suffering from refractory postural tachycardia syndrome.

PubMed

Kanjwal, Khalil; Saeed, Bilal; Karabin, Beverly; Kanjwal, Yousuf; Grubb, Blair P

2012-01-01

Methylphenidate has been shown to be an effective therapy in patients with refractory neurocardiogenic syncope. However, the role of methylphenidate in patients suffering from postural orthostatic tachycardia (POTS) has not been reported. The study was approved by the institutional review board. A retrospective nonrandomized analysis was preformed on 24 patients evaluated at our autonomic center for POTS from 2003 to 2010. The diagnosis of POTS was based on patient history, physical examination, and response to head up tilt table testing. The mean follow-up period was 9 ± 3 months. The patients were included in the current study if they had a diagnosis of POTS with severe symptoms of orthostatic intolerance and were refractory to the commonly used medications. All of these patients were started on methylphenidate and the response to therapy was considered successful if it provided symptomatic relief. Twenty-four patients (age 28 ± 12, 20 women) met inclusion criterion for this study. The response to treatment was assed subjectively in each patient and was collected in a retrospective fashion from patient charts and physician communications. Four patients reported side effects in the form of nausea and 2 ultimately had to discontinue the treatment. Another 4 patients had a follow-up of less than 6 months. Thus, only 18 patients who received methylphenidate completed the follow-up of 6 months. Out of these 18 patients, 14 (77%) patients reported marked improvement in their symptoms. Nine out of 12 patients who had recurrent episodes of syncope reported no syncope at 6 months of follow-up. Fourteen (77%) patients reported marked improvement in their symptoms of fatigue and presyncope. Four patients continue to have symptoms of orthostatic intolerance and 3 continued to have recurrent episodes of syncope. Methylphenidate may be beneficial in patients with otherwise refractory postural tachycardia syndrome.

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.

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.

Improvements in Ionized Cluster-Beam Deposition

NASA Technical Reports Server (NTRS)

Fitzgerald, D. J.; Compton, L. E.; Pawlik, E. V.

1986-01-01

Lower temperatures result in higher purity and fewer equipment problems. In cluster-beam deposition, clusters of atoms formed by adiabatic expansion nozzle and with proper nozzle design, expanding vapor cools sufficiently to become supersaturated and form clusters of material deposited. Clusters are ionized and accelerated in electric field and then impacted on substrate where films form. Improved cluster-beam technique useful for deposition of refractory metals.

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

The influence of high temperatures on selected properties of calcium aluminous composites

NASA Astrophysics Data System (ADS)

KoÅáková, Dana; KoÅ¥átková, Jaroslava; Čáchová, Monika; Vejmelková, Eva; Čechmánek, René; Reiterman, Pavel; Černý, Robert

2017-07-01

The article compares different types of aluminate cements with the reference Portland cement, used in refractory composites. The rate of influence of elevated temperatures (400 °C and 1000 °C) is studied. The investigated parameters are basic physical characteristics and mechanical properties. Results show the best behaviour of the mixture containing Portland cement for the reference state (in the means of all studied parameters); which however after exposition to 1000 °C has the worst performance. Both aluminate cements behave better after heating, which proves its suitability for refractory composites. It is concluded, that the mixture with Gorkal cement achieves the best results.

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.

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.

Refractory metals welded or brazed with tungsten inert gas equipment

NASA Technical Reports Server (NTRS)

Wisner, J. P.

1965-01-01

Appropriate brazing metals and temperatures facilitate the welding or brazing of base metals with tungsten inert gas equipment. The highest quality bond is obtained when TIG welding is performed in an inert atmosphere.

Maritime Cast Shop Integrated Improvement Plan

DTIC Science & Technology

2010-08-20

preclude increasing non-value added revert inventory. A second best practice in this area is the consumption and reuse of revert produced from pigging...alloy elements–minimize metallic oxidation.  Inert gas cost—maximize nitrogen use instead of the more costly argon gas use.  Refractory consumption

Removable Mandrels For Vacuum-Plasma-Spray Forming

NASA Technical Reports Server (NTRS)

Krotz, Phillip D.; Davis, William M.; Power, Christopher A.; Woodford, William H.; Todd, Douglas M.; Liaw, Yoon K.; Holmes, Richard R.; Zimmerman, Frank R.; Mckechnie, Timothy N.

1995-01-01

Improved mandrels developed for use in vacuum-plasma-spray (VPS) forming of refractory metal and ceramic furnace cartridge tubes. Designed so after tubes formed on them by VPS, mandrels shrink away from tubes upon cooling back to room temperature and simply slip out of tube.

Design of high-strength refractory complex solid-solution alloys

DOE PAGES

Singh, Prashant; Sharma, Aayush; Smirnov, A. V.; ...

2018-03-28

Nickel-based superalloys and near-equiatomic high-entropy alloys containing molybdenum are known for higher temperature strength and corrosion resistance. Yet, complex solid-solution alloys offer a huge design space to tune for optimal properties at slightly reduced entropy. For refractory Mo-W-Ta-Ti-Zr, we showcase KKR electronic structure methods via the coherent-potential approximation to identify alloys over five-dimensional design space with improved mechanical properties and necessary global (formation enthalpy) and local (short-range order) stability. Deformation is modeled with classical molecular dynamic simulations, validated from our first-principle data. We predict complex solid-solution alloys of improved stability with greatly enhanced modulus of elasticity (3× at 300 K)more » over near-equiatomic cases, as validated experimentally, and with higher moduli above 500 K over commercial alloys (2.3× at 2000 K). We also show that optimal complex solid-solution alloys are not described well by classical potentials due to critical electronic effects.« less

Design of high-strength refractory complex solid-solution alloys

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

Singh, Prashant; Sharma, Aayush; Smirnov, A. V.

Nickel-based superalloys and near-equiatomic high-entropy alloys containing molybdenum are known for higher temperature strength and corrosion resistance. Yet, complex solid-solution alloys offer a huge design space to tune for optimal properties at slightly reduced entropy. For refractory Mo-W-Ta-Ti-Zr, we showcase KKR electronic structure methods via the coherent-potential approximation to identify alloys over five-dimensional design space with improved mechanical properties and necessary global (formation enthalpy) and local (short-range order) stability. Deformation is modeled with classical molecular dynamic simulations, validated from our first-principle data. We predict complex solid-solution alloys of improved stability with greatly enhanced modulus of elasticity (3× at 300 K)more » over near-equiatomic cases, as validated experimentally, and with higher moduli above 500 K over commercial alloys (2.3× at 2000 K). We also show that optimal complex solid-solution alloys are not described well by classical potentials due to critical electronic effects.« less

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.

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial.

PubMed

Jerkeman, Mats; Eskelund, Christian Winther; Hutchings, Martin; Räty, Riikka; Wader, Karin Fahl; Laurell, Anna; Toldbod, Helle; Pedersen, Lone Bredo; Niemann, Carsten Utoft; Dahl, Christina; Kuitunen, Hanne; Geisler, Christian H; Grønbæk, Kirsten; Kolstad, Arne

2018-03-01

Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data on either regimen alone. In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients aged 18 years or older with relapsed or refractory mantle cell lymphoma who had previously been treated with at least one rituximab-containing regimen, an Eastern Cooperative Oncology Group performance status score of 0-3, and at least one site of measurable disease, and who met criteria for several laboratory-assessed parameters. Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only (cycle duration 56 days), given until disease progression or unacceptable toxicity. In the induction phase, patients received intravenous (375 mg/m 2 ) or subcutaneous (1400 mg) rituximab once a week during cycle 1 and then once every 8 weeks. Oral ibrutinib (560 mg once a day) was given to patients every day in the cycle, whereas oral lenalidomide (15 mg once a day) was given on days 1-21. The primary endpoint was overall response assessed in the intention-to-treat population according to Lugano criteria. Safety analysis included all patients who received the treatment, irrespective of eligibility or duration of treatment. The trial is ongoing, but is no longer accruing patients, and is registered with ClinicalTrials.gov, number NCT02460276. Between April 30, 2015, and June 1, 2016, we enrolled 50 patients with relapsed or refractory mantle cell lymphoma at ten centres in Sweden, Finland, Norway, and Denmark. At a median follow-up of 17·8 months (IQR 14·7-20·9), 38 (76%, 95% CI 63-86) patients had an overall response, including 28 (56%, 42-69) patients who had a complete response and ten (20%, 11-33) who had a partial response. The most common grade 3-4 adverse events were neutropenia (in 19 [38%] of 50 patients), infections (in 11 [22%] patients), and cutaneous toxicity (in seven [14%] patients). There were three treatment-related deaths during the study, two due to sepsis and one due to embolic stroke. Our results provide preliminary evidence that the triplet combination of ibrutinib, lenalidomide, and rituximab is an active regimen in patients with relapsed or refractory mantle cell lymphoma, and should be evaluated in a prospective randomised controlled trial. Janssen and Celgene. Copyright © 2018 Elsevier Ltd. All rights reserved.

Bauxite and alumina

USGS Publications Warehouse

Bray, E.L.

2010-01-01

The article reports on the global market performance of bauxite and alumina in 2009 and presents an outlook for their 2010 performance. There were only several U.S. states that could produce bauxite and bauxitic clays including Georgia, Arkansas, and Alabama. The prices for imported refractory-grade calcined bauxite ranged between 426 U.S. dollars and 554 dollars per ton.