Sample records for severe refractory status

  1. Refractory status epilepticus

    PubMed Central

    Singh, Sanjay P; Agarwal, Shubhi; Faulkner, M

    2014-01-01

    Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED), i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs) and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits. PMID:24791086

  2. Updates in Refractory Status Epilepticus

    PubMed Central

    Mahulikar, Advait; Suchdev, Kushak; Shah, Aashit

    2018-01-01

    Refractory status epilepticus is defined as persistent seizures despite appropriate use of two intravenous medications, one of which is a benzodiazepine. It can be seen in up to 40% of cases of status epilepticus with an acute symptomatic etiology as the most likely cause. New-onset refractory status epilepticus (NORSE) is a recently coined term for refractory status epilepticus where no apparent cause is found after initial testing. A large proportion of NORSE cases are eventually found to have an autoimmune etiology needing immunomodulatory treatment. Management of refractory status epilepticus involves treatment of an underlying etiology in addition to intravenous anesthetics and antiepileptic drugs. Alternative treatment options including diet therapies, electroconvulsive therapy, and surgical resection in case of a focal lesion should be considered. Short-term and long-term outcomes tend to be poor with significant morbidity and mortality with only one-third of patients reaching baseline neurological status. PMID:29854452

  3. 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

  4. 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.

  5. Treatment of Refractory and Super-refractory Status Epilepticus.

    PubMed

    Rai, Samhitha; Drislane, Frank W

    2018-06-19

    Refractory and super-refractory status epilepticus (SE) are serious illnesses with a high risk of morbidity and even fatality. In the setting of refractory generalized convulsive SE (GCSE), there is ample justification to use continuous infusions of highly sedating medications-usually midazolam, pentobarbital, or propofol. Each of these medications has advantages and disadvantages, and the particulars of their use remain controversial. Continuous EEG monitoring is crucial in guiding the management of these critically ill patients: in diagnosis, in detecting relapse, and in adjusting medications. Forms of SE other than GCSE (and its continuation in a "subtle" or nonconvulsive form) should usually be treated far less aggressively, often with nonsedating anti-seizure drugs (ASDs). Management of "non-classic" NCSE in ICUs is very complicated and controversial, and some cases may require aggressive treatment. One of the largest problems in refractory SE (RSE) treatment is withdrawing coma-inducing drugs, as the prolonged ICU courses they prompt often lead to additional complications. In drug withdrawal after control of convulsive SE, nonsedating ASDs can assist; medical management is crucial; and some brief seizures may have to be tolerated. For the most refractory of cases, immunotherapy, ketamine, ketogenic diet, and focal surgery are among several newer or less standard treatments that can be considered. The morbidity and mortality of RSE is substantial, but many patients survive and even return to normal function, so RSE should be treated promptly and as aggressively as the individual patient and type of SE indicate.

  6. Refractory and severe status epilepticus in a patient with ring chromosome 20 syndrome.

    PubMed

    Hirano, Yoshiko; Oguni, Hirokazu; Nagata, Satoru

    2016-09-01

    Ring chromosome 20 [r(20)] syndrome is a rare chromosomal disorder that is characterized by the development of refractory epilepsy during childhood with gradual declines in cognitive performance and behavior. Although the prognoses of seizures and intellectual disability associated with this condition are poor, life-threatening complications have rarely been described. We herein presented a case of a 17-year-old female with [r(20)] syndrome who developed recurrent status epilepticus (SE) at 14years of age that evolved into unremitting SE in spite of vigorous antiepileptic treatments. She was administered thiopental anesthesia for 1year, and was subsequently left in severe neurological sequelae. It is important to note that patients with this syndrome not only have severe epileptic encephalopathy persisting into adulthood, but are also at risk of fatal SE. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

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

    PubMed

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

    2017-06-01

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

  8. 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

  9. 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.

  10. Propofol Infusion Syndrome in Refractory Status Epilepticus

    PubMed Central

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

    2013-01-01

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

  11. Super-Refractory Status Epilepticus: Report of a Case and Review of the Literature.

    PubMed

    Lapenta, Leonardo; Frisullo, Giovanni; Vollono, Catello; Brunetti, Valerio; Giannantoni, Nadia Mariagrazia; Sandroni, Claudio; Di Lella, Giuseppe; Della Marca, Giacomo

    2015-10-01

    Super-refractory status epilepticus (SE; ie, SE continuing or recurring despite 24 hours of general anesthesia) is a severe condition with high percentage of mortality and morbidity. Usually, this condition occurs because of serious brain damage; nevertheless, some patients develop super-refractory SE without identifiable etiology. Although not uncommonly encountered in neurointensive care, scientific data on this condition are still lacking in terms of treatment and prognosis. Herein, we report a case of super-refractory SE with recovery after 50 days, despite electroencephalographic (EEG) and magnetic resonance imaging (MRI) signs traditionally related to poor prognosis. A review of the literature on super-refractory SE is also presented. © EEG and Clinical Neuroscience Society (ECNS) 2014.

  12. Therapeutic burst-suppression coma in pediatric febrile refractory status epilepticus.

    PubMed

    Lin, Jainn-Jim; Chou, Cheng-Che; Lan, Shih-Yun; Hsiao, Hsiang-Ju; Wang, Yu; Chan, Oi-Wa; Hsia, Shao-Hsuan; Wang, Huei-Shyong; Lin, Kuang-Lin

    2017-09-01

    Evidence for the beneficial effect of therapeutic burst-suppression coma in pediatric patients with febrile refractory status epilepticus is limited, and the clinical outcomes of this treatment strategy are largely unknown. Therefore, the aim of this study was to explore the outcomes of therapeutic burst-suppression coma in a series of children with febrile refractory status epilepticus. We retrospectively reviewed consecutive pediatric patients with febrile refractory status epilepticus admitted to our pediatric intensive care unit between January 2000 and December 2013. The clinical characteristics were analyzed. Thirty-five patients (23 boys; age range: 1-18years) were enrolled, of whom 28 (80%) developed super-refractory status epilepticus. All of the patients received the continuous administration of intravenous antiepileptic drugs for febrile refractory status epilepticus, and 26 (74.3%) achieved therapeutic burst-suppression coma. All of the patients received mechanical ventilatory support, and 26 (74.3%) received inotropic agents. Eight (22.9%) patients died within 1month. The neurologically functional outcomes at 6months were good in six (27.3%) of the 22 survivors, of whom two returned to clinical baseline. The patients with therapeutic burst-suppression coma were significantly associated with hemodynamic support than the patients with electrographic seizures control (p=0.03), and had a trend of higher 1-month mortality rate, worse 6months outcomes, and a longer duration of hospitalization. Our results suggest that therapeutic burst-suppression coma to treat febrile refractory status epilepticus may lead to an increased risk of hemodynamic instability and a trend of worse outcomes. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  13. Super-refractory status epilepticus in West China.

    PubMed

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

    2015-07-01

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

  14. Status Epilepticus and Refractory Status Epilepticus Management

    PubMed Central

    Abend, Nicholas S.; Bearden, David; Helbig, Ingo; McGuire, Jennifer; Narula, Sona; Panzer, Jessica A.; Topjian, Alexis; Dlugos, Dennis J.

    2014-01-01

    Status epilepticus (SE) describes persistent or recurring seizures without a return to baseline mental status, and is a common neurologic emergency. SE can occur in the context of epilepsy or may be symptomatic of a wide range of underlying etiologies. The clinician’s aim is to rapidly institute care that simultaneously stabilizes the patient medically, identifies and manages any precipitant conditions, and terminates seizures. Seizure management involves “emergent” treatment with benzodiazepines followed by “urgent” therapy with other anti-seizure medications. If seizures persist then refractory SE is diagnosed and management options include additional anti-seizure medications or infusions of midazolam or pentobarbital. This paper reviews the management of pediatric SE and RSE. PMID:25727508

  15. Refractory status epilepticus complicated by drug-induced involuntary movements.

    PubMed

    Nair, Pradeep Pankajakshan; Wadwekar, Vaibhav; Murgai, Aditya; Narayan, Sunil K

    2014-02-11

    New onset refractory status epilepticus (NORSE) is a neurological emergency and difficult to treat condition. We report a case of involuntary movements resulting from thiopentone sodium infusion during the management of refractory status epilepticus. A young woman was admitted with fever and NORSE in the neurology intensive care unit. In addition to supportive measures, she was treated with intravenous lorazepam, phenytoin sodium, sodium valproate, midazolam and thiopentone sodium. While on thiopentone sodium, she developed involuntary twitches involving her upper limbs and face with EEG showing no evidence of ongoing status epilepticus. Because of the temporal relationship with thiopentone infusion, we tapered the dose of thiopentone sodium, which resulted in the disappearance of the movements. The patient recovered well with no recurrence of the seizures during the hospital stay.

  16. [Treatment of refractory status epilepticus with topiramate. Report of three cases].

    PubMed

    Soler, Bernardita; Godoy, Jaime; Mellado Talesnik, Patricio

    2009-07-01

    Refractory status epilepticus is a catastrophic illness of the central nervous system, with a mortality rate that reaches 50%. We report three patients admitted with refractory status epilepticus: a 24 year-old male that discontinued antiepileptic medications, a 46 year-old male with a focal epilepsy secondary to an encephalitis that discontinued medications due to gastrointestinal problems and a 59 year-old male with an ischemic encephalopathy AH were treated with topiramate, delivered through a nasogastric tube with a good response.

  17. Management of refractory status epilepticus in adults

    PubMed Central

    Rossetti, Andrea O.; Lowenstein, Daniel H.

    2011-01-01

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

  18. Refractory status epilepticus and autoimmune encephalitis with GABAAR and GAD65 antibodies: A case report.

    PubMed

    Gagnon, Maude-Marie; Savard, Martin; Mourabit Amari, Karim

    2016-04-01

    Autoimmune encephalitis is an inflammatory disorder of the brain that may be associated with different neuronal antibodies. Recently, an increasing number of valuable autoantibodies have been identified, including GABAAR antibodies, which appear to be associated with a severe form of encephalitis with refractory status epilepticus. We report here on a patient with encephalitis associated with GAD65 and GABAAR antibodies, an entity that remains an understudied topic, with an unanticipated clinical presentation and we describe the longitudinal follow-up. We report a case of encephalitis associated with GAD65 and GABAAR antibodies; we describe clinical and paraclinical features and the longitudinal follow-up. Our case presented with dysgueusia, dysosmia and episodes of hyperventilation that evolved into a refractory status epilepticus. Multiple anticonvulsant drugs were required. An aggressive immunotherapy was associated with a relative favorable outcome, in regard of epilepsy and cognitive functions. However, a relapse occurred and a full recovery was not observed at the last follow-up visit. There was no correlation between GAD65 antibodies titers and disease activity. Autoimmune encephalitis associated with GABAAR and GAD65 antibodies might be a severe and refractory disease. The appropriate treatment is currently unknown for those patients. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  19. Evaluation of nutritional status in children with refractory epilepsy

    PubMed Central

    Bertoli, S; Cardinali, S; Veggiotti, P; Trentani, C; Testolin, G; Tagliabue, A

    2006-01-01

    Background children affected by refractory epilepsy could be at risk of malnutrition because of feeding difficulties (anorexia, chewing, swallowing difficulties or vomiting) and chronic use of anticonvulsants, which may affect food intake and energy metabolism. Moreover, their energy requirement may be changed as their disabilities would impede normal daily activities. The aim of the present study was to evaluate nutritional status, energy metabolism and food intake in children with refractory epilepsy. Methods 17 children with refractory epilepsy (13 boys and 4 girls; mean age 9 ± 3,2 years; Body Mass Index 15,7 ± 3,6) underwent an anthropometric assessment, body composition evaluation by dual-energy X-ray absorptiometry, detailed dietetic survey and measurement of resting energy expenditure by indirect calorimetry. Weight-for-age, height-for-age (stunting) and weight-for-height (wasting) were estimated compared to those of a reference population of the same age. Results 40% of children were malnourished and 24% were wasted. The nutritional status was worse in the more disabled children. Dietary intake resulted unbalanced (18%, 39%, 43% of total daily energy intake derived respectively from protein, lipid and carbohydrate). Adequacy index [nutrient daily intake/recommended allowance (RDA) × 100] was < 60% for calcium iron and zinc. Conclusion many children with refractory epilepsy would benefit from individual nutritional assessment and management as part of their overall care. PMID:16640779

  20. Evaluation of nutritional status in children with refractory epilepsy.

    PubMed

    Bertoli, S; Cardinali, S; Veggiotti, P; Trentani, C; Testolin, G; Tagliabue, A

    2006-04-26

    children affected by refractory epilepsy could be at risk of malnutrition because of feeding difficulties (anorexia, chewing, swallowing difficulties or vomiting) and chronic use of anticonvulsants, which may affect food intake and energy metabolism. Moreover, their energy requirement may be changed as their disabilities would impede normal daily activities. The aim of the present study was to evaluate nutritional status, energy metabolism and food intake in children with refractory epilepsy. 17 children with refractory epilepsy (13 boys and 4 girls; mean age 9 +/- 3,2 years; Body Mass Index 15,7 +/- 3,6) underwent an anthropometric assessment, body composition evaluation by dual-energy X-ray absorptiometry, detailed dietetic survey and measurement of resting energy expenditure by indirect calorimetry. Weight-for-age, height-for-age (stunting) and weight-for-height (wasting) were estimated compared to those of a reference population of the same age. 40% of children were malnourished and 24% were wasted. The nutritional status was worse in the more disabled children. Dietary intake resulted unbalanced (18%, 39%, 43% of total daily energy intake derived respectively from protein, lipid and carbohydrate). Adequacy index [nutrient daily intake/recommended allowance (RDA) x 100] was < 60% for calcium iron and zinc. many children with refractory epilepsy would benefit from individual nutritional assessment and management as part of their overall care.

  1. Spectrum and Predictors of Refractory Status Epilepticus in a Developing Country.

    PubMed

    Dubey, Deepanshu; Bhoi, Sanjeev K; Kalita, Jayantee; Misra, Usha K

    2017-09-01

    Refractory status epilepticus (RSE) can influence the outcome of status epilepticus (SE). In the present study, we report the aetiology and predictors of outcomes of RSE in a developing country. This is a prospective hospital-based study of SE patients (continuous seizures for five minutes or more). Those who had SE persisting after two antiepileptic drugs were defined as having RSE. We present the demographic information, duration, and type of SE, and we note its severity using the status epilepticus severity score (STESS), its aetiology, comorbidities and imaging findings. The outcome of RSE was defined as cessation of seizures and the condition upon discharge, as assessed by the modified Rankin Scale. A total of 35 (42.5%) of our 81 patients had RSE. The median duration of SE before starting treatment was 2 hours (range=0.008-160 h). The most common causes of RSE were stroke in 5 (14.3%), central nervous system (CNS) infections in 12 (34.3%) and metabolic encephalopathies in 13 (37.1%) patients. Some 21 (60%) patients had comorbidities, and the STESS was favourable in 7 (20%) patients. A total of 14 (20%) patients died, but death was directly related to SE in only one of these. Some 10 patients had super-refractory status epilepticus, which was due to CNS infection in 5 (50%) and metabolic encephalopathy in 3 (30%). On multivariate analysis, an unfavourable STESS (p=0.05) and duration of SE before treatment (p=0.01) predicted RSE. Metabolic aetiology (p=0.05), mechanical ventilation (p60 years (p=0.003) were predictors of poor outcomes. RSE was common (42.5%) among patients with SE in a tertiary care center in India. It was associated with high mortality and poor outcomes. Age above 60 years and metabolic aetiology were found to be predictors of poor outcomes.

  2. A Study of Super Refractory Status Epilepticus from India.

    PubMed

    Misra, Usha K; Kalita, Jayantee; Dubey, Deepanshu

    2017-01-01

    Super refractory status epilepticus (SRSE) is an important and recently recognized neurological emergency. In view of paucity of studies on SRSE, we report the frequency, etiology and outcome of SRSE. In a hospital-based observational study during 2013 to 2016, consecutive patients with SRSE [persistence of status epilepticus (SE) for 24 h or more, or recurrence of SE on weaning of intravenous anesthetic] were included. The demographic, clinical, and laboratory data were obtained and the severity of SE was defined using Status Epilepticus Severity Score (STESS). The outcome was defined as control of SE, hospital death, and functional status at the time of discharge. Fourteen (13%) patients developed SRSE. Their median age was 27.5 (2-70) years and four were below 18 years of age. The etiology of SRSE was metabolic encephalopathy and encephalitis in five patients each, cerebral venous sinus thrombosis in one and miscellaneous disorders in three patients. Six (43%) patients died. The patients with SRSE had higher admission STESS ( p  = 0.04), and longer intensive care unit ( p  < 0.01) and hospital ( p  = 0.004) stay compared to non-SRSE group. The patients with treatable etiology had better outcome. SRSE occurred in 13% patients with SE and 43% of them died. The SRSE patients with treatable etiology had a better outcome.

  3. 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.

  4. Refractory status epilepticus and glutamic acid decarboxylase antibodies in adults: presentation, treatment and outcomes.

    PubMed

    Khawaja, Ayaz M; Vines, Brannon L; Miller, David W; Szaflarski, Jerzy P; Amara, Amy W

    2016-03-01

    Glutamic acid decarboxylase antibodies (GAD-Abs) have been implicated in refractory epilepsy. The association with refractory status epilepticus in adults has been rarely described. We discuss our experience in managing three adult patients who presented with refractory status epilepticus associated with GAD-Abs. Case series with retrospective chart and literature review. Three patients without pre-existing epilepsy who presented to our institution with generalized seizures between 2013 and 2014 were identified. Seizures proved refractory to first and second-line therapies and persisted beyond 24 hours. Patient 1 was a 22-year-old female who had elevated serum GAD-Ab titres at 0.49 mmol/l (normal: <0.02) and was treated with multiple immuno- and chemotherapies, with eventual partial seizure control. Patient 2 was a 61-year-old black female whose serum GAD-Ab titre was 0.08 mmol/l. EEG showed persistent generalized periodic discharges despite maximized therapy with anticonvulsants but no immunotherapy, resulting in withdrawal of care and discharge to nursing home. Patient 3 was a 50-year-old black female whose serum GAD-Ab titre was 0.08 mmol/l, and was discovered to have pulmonary sarcoidosis. Treatment with steroids and intravenous immunoglobulin resulted in seizure resolution. Due to the responsiveness to immunotherapy, there may be an association between GAD-Abs and refractory seizures, including refractory status epilepticus. Causation cannot be established since GAD-Abs may be elevated secondary to concurrent autoimmune diseases or formed de novo in response to GAD antigen exposure by neuronal injury. Based on this report and available literature, there may be a role for immuno- and chemotherapy in the management of refractory status epilepticus associated with GAD-Abs.

  5. Preliminary results of the global audit of treatment of refractory status epilepticus.

    PubMed

    Ferlisi, M; Hocker, S; Grade, M; Trinka, E; Shorvon, S

    2015-08-01

    The treatment of refractory and super refractory status epilepticus is a "terra incognita" from the point of view of evidence-based medicine. As randomized or controlled studies that are sufficiently powered are not feasible in relation to the many therapies and treatment approaches available, we carried out an online multinational audit (registry) in which neurologists or intensivists caring for patients with status epilepticus may prospectively enter patients who required general anesthesia to control the status epilepticus (SE). To date, 488 cases from 44 different countries have been collected. Most of the patients had no history of epilepsy and had a cryptogenic etiology. First-line treatment was delayed and not in line with current guidelines. The most widely used anesthetic of first choice was midazolam (59%), followed by propofol and barbiturates. Ketamine was used in most severe cases. Other therapies were administered in 35% of the cases, mainly steroids and immunotherapy. Seizure control was achieved in 74% of the patients. Twenty-two percent of patients died during treatment, and four percent had treatment actively withdrawn because of an anticipated poor outcome. The neurological outcome was good in 36% and poor in 39.3% of cases, while 25% died during hospitalization. Factors that positively influenced outcome were younger age, history of epilepsy, and low number of different anesthetics tried. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015. Published by Elsevier Inc.

  6. Transient bradycardia induced by thiopentone sodium: a unique challenge in the management of refractory status epilepticus

    PubMed Central

    Sharma, Sushma; Nair, Pradeep P; Murgai, Aditya; Selvaraj, Raja J

    2013-01-01

    Thiopentone sodium is one of the important drugs in the armamentarium for terminating refractory status epilepticus, a neurological emergency. We report a case of thiopentone-related bradycardia during the management of the new onset refractory status epilepticus in a young man, which was circumvented by prophylactic insertion of temporary pacemaker while thiopentone infusion was continued. A systematic approach was employed to manage the status epilepticus, including infusion of thiamine and glucose followed by antiepileptic drugs. The patient was ventilated and infused with lorazepam, phenytoin, sodium valproate, levetiracetam and midazolam followed by thiopentone sodium. With the introduction of thiopentone the seizures could be controlled but the patient developed severe bradycardia and junctional rhythm. The bradycardia disappeared when thiopentone was withdrawn and reappeared when the drug was reintroduced. Propofol infusion was tried with no respite in seizures. Later thiopentone sodium was reintroduced after inserting temporary cardiac pacemaker. Seizure was controlled and patient was weaned off the ventilator. PMID:24130206

  7. Transient bradycardia induced by thiopentone sodium: a unique challenge in the management of refractory status epilepticus.

    PubMed

    Sharma, Sushma; Nair, Pradeep P; Murgai, Aditya; Selvaraj, Raja J

    2013-10-15

    Thiopentone sodium is one of the important drugs in the armamentarium for terminating refractory status epilepticus, a neurological emergency. We report a case of thiopentone-related bradycardia during the management of the new onset refractory status epilepticus in a young man, which was circumvented by prophylactic insertion of temporary pacemaker while thiopentone infusion was continued. A systematic approach was employed to manage the status epilepticus, including infusion of thiamine and glucose followed by antiepileptic drugs. The patient was ventilated and infused with lorazepam, phenytoin, sodium valproate, levetiracetam and midazolam followed by thiopentone sodium. With the introduction of thiopentone the seizures could be controlled but the patient developed severe bradycardia and junctional rhythm. The bradycardia disappeared when thiopentone was withdrawn and reappeared when the drug was reintroduced. Propofol infusion was tried with no respite in seizures. Later thiopentone sodium was reintroduced after inserting temporary cardiac pacemaker. Seizure was controlled and patient was weaned off the ventilator.

  8. Management of severe and/or refractory epistaxis.

    PubMed

    García-Cabo, Patricia; Fernández-Vañes, Laura; Pedregal, Daniel; Menéndez Del Castro, Marta; Murias, Eduardo; Vega, Pedro; Llorente, José Luis; Rodrigo, Juan Pablo; López, Fernando

    2018-05-18

    The objective was to determine the results of the treatment of severe and/or refractory epistaxis requiring hospital admission. In addition, the results of arterial ligation versus embolization were compared. Sixty-three patients with severe and/or refractory epistaxis requiring hospital admission between August 2014 and December 2016 were included prospectively. Eleven patients (17%) underwent embolization, 5 (8%) endoscopy ligation and the remaining 47 (75%) underwent conservative treatment with tamponade. The mean age of the patients in which conservative measures were sufficient was 72 years, while the age of those treated with embolization was 71 years and of those who underwent surgery was 53 years. For the patients who underwent conservative treatment or surgery, the average stay was 6 days, compared to 9 days for those who underwent embolization. One patient suffered a hemispheric stroke after embolization. No post-surgical complications were observed. Most cases of severe and/or refractory epistaxis are resolved by conventional tamponade. Endoscopy ligation is associated with a decrease in hospital stay, without serious complications. It is advisable to have all the possible therapeutic options available, for which the presence of interventional radiologists and experienced surgeons is essential to avoid complications and decide the treatment to be performed individually for each patient. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Ketamine infusion for refractory status epilepticus: A case report of cardiac arrest.

    PubMed

    Koffman, Lauren; Yan Yiu, Ho; Farrokh, Salia; Lewin, John; Geocadin, Romergryko; Ziai, Wendy

    2018-01-01

    Refractory status epilepticus (RSE) has a high mortality rate and is often difficult to treat. When traditional therapies fail ketamine may be considered. There are limited reports of adverse cardiac events with the use of ketamine for RSE and no reports of cardiac arrest in this context. Evaluate the occurrence of cardiac arrhythmias associated with the use of ketamine for RSE. Retrospective chart review of nine patients who underwent ketamine infusion for RSE. Etiology of refractory status epilepticus included autoimmune/infectious process (Zeiler et al., 2014), ischemic stroke (Bleck, 2005) and subarachnoid hemorrhage (Bleck, 2005). Of the nine patients who received ketamine, two had documented cardiac events; one remained clinically stable and the other developed multiple arrhythmias, including recurrent episodes of asystole. Once ketamine was discontinued the latter patient stabilized with the addition of anti arrhythmic therapy. Ketamine is utilized to treat refractory status epilepticus, but should be used with caution in patients with subarachnoid hemorrhage, as there may be an increased risk of life threatening arrhythmias and cardiac arrest. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Intravenous ketogenic diet therapy for treatment of the acute stage of super-refractory status epilepticus in a pediatric patient.

    PubMed

    Lin, Jainn-Jim; Lin, Kuang-Lin; Chan, Oi-Wa; Hsia, Shao-Hsuan; Wang, Huei-Shyong

    2015-04-01

    A ketogenic diet has been used successfully to treat intractable epilepsy. However, the role of early intravenous initiation of ketogenic diet in the acute phase of super-refractory status epilepticus is not well-described. An intravenous ketogenic diet was administered to a boy with super-refractory status epilepticus. At 24 hours after intravenous ketogenic diet, moderate ketosis appeared, and thiamylal was successfully weaned at 70 hours after admission. An intravenous ketogenic regimen led to subsequent ketosis and seizure control in a child with super-refractory status epilepticus. Early induction of ketosis may be a novel strategy to effectively treat super-refractory status epilepticus. Although there are few data regarding the early use of intravenous ketogenic diet in the treatment of super-refractory status epilepticus, it may be considered an alternative option. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. A one-year prospective study of refractory status epilepticus in Modena, Italy.

    PubMed

    Giovannini, Giada; Monti, Giulia; Polisi, Michela M; Mirandola, Laura; Marudi, Andrea; Pinelli, Giovanni; Valzania, Franco; Girardis, Massimo; Nichelli, Paolo F; Meletti, Stefano

    2015-08-01

    Refractory status epilepticus (RSE) is a particular critical condition characterized by seizures that continue despite the use of first- and second-line therapies and by high mortality. To date, only one prospective study investigated clinical features and prognostic factors in RSE. In this study, we performed a one-year prospective survey to identify clinical features, outcomes, and variables associated with the development of RSE in the adolescent and adult population of Modena, northern Italy. We observed 83 episodes of SE in 83 patients. In 31% of the cases, third-line therapy (anesthetic drug) was needed. Among this group, 14% resolved and were classified as RSE, while, in 17%, seizures recurred at withdrawal of anesthetics and were classified as super-RSE. The development of RSE/super-RSE was associated with a stuporous/comatose state at presentation and with the absence of a previous history of epilepsy. Refractory status epilepticus/super-refractory status epilepticus showed a worse outcome compared with responsive SE: 54% versus 21% for 30-day mortality; 19% versus 56% for a return to baseline condition. This prospective study confirms stupor/coma at onset as a relevant clinical factor associated with SE refractoriness. We observed a rate of RSE comparable with previous reports, with high mortality and morbidity. Mortality in the observed RSE was higher than in previous studies; this result is probably related to the low rate of a previous epilepsy history in our population that reflects a high incidence of acute symptomatic etiologies, especially the inclusion of patients with postanoxic SE who have a bad prognosis per se. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

  12. 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.

  13. Mortality, morbidity and refractoriness prediction in status epilepticus: Comparison of STESS and EMSE scores.

    PubMed

    Giovannini, Giada; Monti, Giulia; Tondelli, Manuela; Marudi, Andrea; Valzania, Franco; Leitinger, Markus; Trinka, Eugen; Meletti, Stefano

    2017-03-01

    Status epilepticus (SE) is a neurological emergency, characterized by high short-term morbidity and mortality. We evaluated and compared two scores that have been developed to evaluate status epilepticus prognosis: STESS (Status Epilepticus Severity Score) and EMSE (Epidemiology based Mortality score in Status Epilepticus). A prospective observational study was performed on consecutive patients with SE admitted between September 2013 and August 2015. Demographics, clinical variables, STESS-3 and -4, and EMSE-64 scores were calculated for each patient at baseline. SE drug response, 30-day mortality and morbidity were the outcomes measure. 162 episodes of SE were observed: 69% had a STESS ≥3; 34% had a STESS ≥4; 51% patients had an EMSE ≥64. The 30-days mortality was 31.5%: EMSE-64 showed greater negative predictive value (NPV) (97.5%), positive predictive value (PPV) (59.8%) and accuracy in the prediction of death than STESS-3 and STESS-4 (p<0.001). At 30 days, the clinical condition had deteriorated in 59% of the cases: EMSE-64 showed greater NPV (71.3%), PPV (87.8%) and accuracy than STESS-3 and STESS-4 (p<0.001) in the prediction of this outcome. In 23% of all cases, status epilepticus proved refractory to non-anaesthetic treatment. All three scales showed a high NPV (EMSE-64: 87.3%; STESS-4: 89.4%; STESS-3: 87.5%) but a low PPV (EMSE-64: 40.9%; STESS-4: 52.9%; STESS-3: 32%) for the prediction of refractoriness to first and second line drugs. This means that accuracy for the prediction of refractoriness was equally poor for all scales. EMSE-64 appears superior to STESS-3 and STESS-4 in the prediction of 30-days mortality and morbidity. All scales showed poor accuracy in the prediction of response to first and second line antiepileptic drugs. At present, there are no reliable scores capable of predicting treatment responsiveness. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  14. Severe and Refractory Hypertension in a Young Woman

    PubMed Central

    Cuadra, René H; White, William B

    2016-01-01

    Background Refractory hypertension in a young person is an uncommon clinical problem, but one that may be referred to hypertension specialists. Factitious hypertension is fortunately quite rare, but should be considered when evaluating patients who are refractory to numerous classes of antihypertensive therapies and have failed to achieve control despite input from multiple providers. Report of a Case A 19 year old woman was referred to us after failing to achieve blood pressure control by a primary physician and 2 subspecialists in nephrology and hypertension; she also had numerous emergency department visits for symptomatic and severe hypertension. Exhaustive diagnostic testing for secondary causes and witnessed medication dosing in an outpatient setting was unrevealing. Subsequent inpatient admission demonstrated normalization of BPs with small doses of intravenous antihypertensive agents. During the hospitalization, she was observed “pocketing” her oral medications in the buccal folds, and then discarding them in a trash container. Confrontation by psychiatrists and the hypertension specialists led to the admission that she had learned to start and stop beta-blockers and clonidine to induce severe, rebound hypertension. Discussion Factitious and induced hypertension is a rare cause of resistant or refractory hypertension. Nevertheless, hypertension specialists should suspect the diagnosis when there is a history of visits to multiple institutions and physicians, negative secondary workup, absence of overt target organ damage, history of psychiatric illness, and employment in the medical field. PMID:27160032

  15. Early Use of the NMDA Receptor Antagonist Ketamine in Refractory and Superrefractory Status Epilepticus

    PubMed Central

    Zeiler, F. A.

    2015-01-01

    Refractory status epilepticus (RSE) and superrefractory status epilepticus (SRSE) pose a difficult clinical challenge. Multiple cerebral receptor and transporter changes occur with prolonged status epilepticus leading to pharmacoresistance patterns unfavorable for conventional antiepileptics. In particular, n-methyl-d-aspartate (NMDA) receptor upregulation leads to glutamate mediated excitotoxicity. Targeting these NMDA receptors may provide a novel approach to otherwise refractory seizures. Ketamine has been utilized in RSE. Recent systematic review indicates 56.5% and 63.5% cessation in seizures in adults and pediatrics, respectively. No complications were described. We should consider earlier implementation of ketamine or other NMDA receptor antagonists, for RSE. Prospective study of early implementation of ketamine should shed light on the role of such medications in RSE. PMID:25649724

  16. Supra-recommendation Treatment of Super-refractory Status Epilepticus.

    PubMed

    Vyas, Devashish Dhiren; Dash, Gopal Krishna

    2016-06-01

    A 28-year old female was admitted with recurrent seizures following 2 days of febrile illness, after which she developed status epilepticus. Midazolam and later thiopentone infusions were started after failure of regular intravenous antiepileptics. Burst suppression was achieved at doses of 3 mg/kg/hr for midazolam and 6 mg/kg/hr of thiopentone. Adjunctive medications included methylprednisolone, intravenous immunoglobulin and acyclovir. Imaging and biochemical parameters were normal. She required 3 cycles of midazolam and 2 cycles of thiopentone for complete cessation of seizures. She recovered with mild attentional and recent memory deficits on follow up. Treatment of super-refractory status epilepticus requires individualized regimens and may need doses beyond conventional limits. To the best of our knowledge, there is no such reported case from India.

  17. 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

  18. 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.

  19. 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.

  20. Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital.

    PubMed

    Tasker, Robert C; Goodkin, Howard P; Sánchez Fernández, Iván; Chapman, Kevin E; Abend, Nicholas S; Arya, Ravindra; Brenton, James N; Carpenter, Jessica L; Gaillard, William D; Glauser, Tracy A; Goldstein, Joshua; Helseth, Ashley R; Jackson, Michele C; Kapur, Kush; Mikati, Mohamad A; Peariso, Katrina; Wainwright, Mark S; Wilfong, Angus A; Williams, Korwyn; Loddenkemper, Tobias

    2016-10-01

    To describe pediatric patients with convulsive refractory status epilepticus in whom there is intention to use an IV anesthetic for seizure control. Two-year prospective observational study evaluating patients (age range, 1 mo to 21 yr) with refractory status epilepticus not responding to two antiepileptic drug classes and treated with continuous infusion of anesthetic agent. Nine pediatric hospitals in the United States. In a cohort of 111 patients with refractory status epilepticus (median age, 3.7 yr; 50% male), 54 (49%) underwent continuous infusion of anesthetic treatment. The median (interquartile range) ICU length of stay was 10 (3-20) days. Up to four "cycles" of serial anesthetic therapy were used, and seizure termination was achieved in 94% by the second cycle. Seizure duration in controlled patients was 5.9 (1.9-34) hours for the first cycle and longer when a second cycle was required (30 [4-120] hr; p = 0.048). Midazolam was the most frequent first-line anesthetic agent (78%); pentobarbital was the most frequently used second-line agent after midazolam failure (82%). An electroencephalographic endpoint was used in over half of the patients; higher midazolam dosing was used with a burst suppression endpoint. In midazolam nonresponders, transition to a second agent occurred after a median of 1 day. Most patients (94%) experienced seizure termination with these two therapies. Midazolam and pentobarbital remain the mainstay of continuous infusion therapy for refractory status epilepticus in the pediatric patient. The majority of patients experience seizure termination within a median of 30 hours. These data have implications for the design and feasibility of future intervention trials. That is, testing a new anesthetic anticonvulsant after failure of both midazolam and pentobarbital is unlikely to be feasible in a pediatric study, whereas a decision to test an alternative to pentobarbital, after midazolam failure, may be possible in a multicenter

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

    PubMed

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

    2014-07-01

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

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

    PubMed

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

    2018-04-01

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

  3. Perioperative management of massive fat embolism syndrome presenting as refractory status epilepticus

    PubMed Central

    Watson, William; Louro, Jack; Dudaryk, Roman

    2018-01-01

    Fat embolism syndrome (FES) most commonly can occur after trauma in patients with long bone fractures. While the majority of FES cases present as a mild decrease in mental status, some may manifest as seizure activity. We describe a case of a young patient with traumatic fractures who developed FES leading to refractory status epilepticus and simultaneously required damage controlled orthopedic surgery. The role of imaging modalities including magnetic resonance imaging, transcranial Doppler, and transesophageal echocardiography in diagnosis is discussed, and a multidisciplinary approach to successful perioperative management is described.

  4. The ketogenic diet as broad-spectrum treatment for super-refractory pediatric status epilepticus: challenges in implementation in the pediatric and neonatal intensive care units.

    PubMed

    Cobo, Nicole H; Sankar, Raman; Murata, Kristina K; Sewak, Sarika L; Kezele, Michele A; Matsumoto, Joyce H

    2015-02-01

    Refractory status epilepticus carries significant morbidity and mortality. Recent reports have promoted the use of the ketogenic diet as an effective treatment for refractory status epilepticus. We describe our recent experience with instituting the ketogenic diet for 4 critically ill children in refractory status epilepticus, ranging in age from 9 weeks to 13.5 years after failure of traditional treatment. The ketogenic diet allowed these patients to be weaned off continuous infusions of anesthetics without recurrence of status epilepticus, though delayed ketosis and persistently elevated glucose measurements posed special challenges to effective initiation, and none experienced complete seizure cessation. The ease of sustaining myocardial function with fatty acid energy substrates compares favorably over the myocardial toxicity posed by anesthetic doses of barbiturates and contributes to the safety profile of the ketogenic diet. The ketogenic diet can be implemented successfully and safely for the treatment of refractory status epilepticus in pediatric patients. © The Author(s) 2014.

  5. Intravenous levetiracetam terminates refractory status epilepticus in two patients with migrating partial seizures in infancy.

    PubMed

    Cilio, Maria Roberta; Bianchi, Roberto; Balestri, Martina; Onofri, Alfredo; Giovannini, Simona; Di Capua, Matteo; Vigevano, Federico

    2009-09-01

    To evaluate the efficacy and tolerability of intravenous (IV) levetiracetam in refractory status epilepticus of migrating partial seizures in infancy (MPSI). IV levetiracetam was infused in two infants, first as a loading dose of 60mg/kg in 30min, then at 30mg/kg twice a day. Both infants were continuously monitored with video-EEG before, during and after the drug trial. Blood count, liver enzymes, serum creatinine, ammonia and lactate blood levels were performed repeatedly before and after the IV levetiracetam administration. Follow-up was of 16 and 10 months. EEG monitoring allowed the diagnosis of MPSI, showing the typical seizures pattern in both patients. IV levetiracetam was effective in stopping status epilepticus in both infants. Levetiracetam also prevented the recurrence of status epilepticus during follow-up. No adverse reactions were observed during the infusion phase or during follow-up. MPSI is a newly recognized epileptic syndrome characterized by early onset of intractable partial seizures arisingly independently and sequentially from both hemispheres, migrating from one region of the brain to another and from one hemisphere to another. We report the efficacy of intravenous levetiracetam in resolving refractory status epilepticus in two infants with this new epilepsy syndrome.

  6. 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.

  7. Drug-refractory aggression, self-injurious behavior, and severe tantrums in autism spectrum disorders: a chart review study.

    PubMed

    Adler, Benjamin A; Wink, Logan K; Early, Maureen; Shaffer, Rebecca; Minshawi, Noha; McDougle, Christopher J; Erickson, Craig A

    2015-01-01

    Aggression, self-injurious behavior, and severe tantrums are impairing symptoms frequently experienced by individuals with autism spectrum disorders. Despite US Food and Drug Administration approval of two atypical antipsychotics targeting these symptoms in youth with autistic disorder, they remain frequently drug refractory. We define drug-refractory aggression, self-injurious behavior, and severe tantrums in people with autism spectrum disorders as behavioral symptoms requiring medication adjustment despite previous trials of risperidone and aripiprazole or previous trials of three psychotropic drugs targeting the symptom cluster, one of which was risperidone or aripiprazole. We reviewed the medical records of individuals of all ages referred to our clinic for autism spectrum disorder diagnostic evaluation, as well as pharmacotherapy follow-up notes for all people meeting autism spectrum disorder criteria, for drug-refractory symptoms. Among 250 consecutively referred individuals, 135 met autism spectrum disorder and enrollment criteria, and 53 of these individuals met drug-refractory symptom criteria. Factors associated with drug-refractory symptoms included age 12 years or older (p < 0.0001), diagnosis of autistic disorder (p = 0.0139), and presence of intellectual disability (p = 0.0273). This pilot report underscores the significance of drug-refractory aggression, self-injurious behavior, and severe tantrums; suggests the need for future study clarifying factors related to symptom development; and identifies the need for focused treatment study of this impairing symptom domain. © The Author(s) 2014.

  8. Study of Refractory Status Epilepticus from a Tertiary Care Center.

    PubMed

    Kohli, Sahil; Pasangulapati, Suresh Babu; Yoganathan, Sangeetha; Rynjah, Gideon Lyngsyun; Prabhakar, A T; Aaron, Sanjith; Alexander, Mathew; Mathew, Vivek

    2017-01-01

    To determine the proportion of refractory status epilepticus (RSE) and super-RSE (SRSE) among patients with status epilepticus (SE) and to analyze RSE and non-RSE (NRSE) in terms of etiology and predictors for RSE. Patients were identified from discharge summaries database with keywords of SE and records of the portable electroencephalogram (EEG) machine from January 2011 to March 2016. Two hundred and eighteen events were included in the study with 114 (52.3%) males, bimodal age preponderance age <5 years 30%, and second peak in age 15-65 years 52.8%, preexisting seizures were present in 34.4% ( n = 75). Nearly 77.1% had NRSE ( n = 168) and 22.9% had RSE ( n = 50). This included 17 patients with SRSE ( n = 17, 7.8% of all SE). Central nervous system (CNS) infection was a single largest etiological group in SE (69/218, 31.7%). In RSE, autoimmune encephalitis (17/50) and CNS infection (13/50) were the largest groups. De novo seizures ( P = 0.007), low sensorium at admission ( P = 0.001), low albumin at admission ( P = 0.002), and first EEG being abnormal ( P = 0.001) were risk factors on bivariate analysis. An unfavorable status epilepticus severity score (STESS) was predictive for RSE ( P = 0.001). On multivariate analysis, de novo seizures ( P = 0.009) and abnormal EEG at admission ( P = 0.03) were predictive for RSE. Fifty patients had RSE (22.9%), of which 17 went on to become SRSE (7.8%). Unfavorable STESS score was predictive for RSE on bivariate analysis. On multivariate analysis, de novo seizures and abnormal initial EEG were predictors of RSE.

  9. Use of ustekinumab for severe refractory atopic dermatitis in a young teenager.

    PubMed

    Wlodek, C; Hewitt, H; Kennedy, C T

    2016-08-01

    When conventional systemic immunosuppressive treatments fail in the setting of severe eczema, unlike in psoriasis, there are limited treatment options and only anecdotal evidence to help guide clinicians. There is a growing body of evidence for the use of certain biologic agents for moderate to severe eczema. We report the youngest case to date successfully and safely treated with ustekinumab for severe refractory atopic dermatitis. © 2016 British Association of Dermatologists.

  10. Low-dose oral microemulsion ciclosporin for severe, refractory ulcerative colitis.

    PubMed

    de Saussure, P; Soravia, C; Morel, P; Hadengue, A

    2005-08-01

    The optimal modalities of treatment with oral microemulsion ciclosporin in patients with severe, steroid-refractory ulcerative colitis are uncertain. To assess the applicability, in terms of efficacy and tolerability, of a standard oral microemulsion ciclosporin treatment protocol targeting relatively low blood ciclosporin concentrations, in patients with severe, steroid-resistant ulcerative colitis. Patients with a severe attack of ulcerative colitis and no satisfactory response to intravenous corticosteroids were started on oral microemulsion ciclosporin. Dosages were adapted according to a standard protocol, targeting a blood predose ciclosporin concentration (C0) of 100-200 ng/mL. Patients without a clinical response on day 8 were scheduled for colectomy. Sixteen patients were enrolled. A clinical response was observed in 14/16 (88%). The mean clinical activity index scores and concentrations of C-reactive protein on days 0, 4 and 8 were 11.8, 6.7 and 4.1, and 50.3, 19.3 and 9.7 mg/L respectively. The mean C0 (days 0-8) was 149 pg/mL. The mean creatinine clearance rates on days 0 and 8 were 88 and 96 mL/min. One patient had an acute elevation of transaminases that resulted in discontinuing ciclosporin. Even when dosed for a target C0 of 100-200 ng/mL, oral microemulsion ciclosporin for severe, steroid-refractory ulcerative colitis achieves an efficacy similar to that attained with higher, potentially more toxic levels. The oral route should replace intravenous treatment in this clinical setting.

  11. 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.

  12. Factors associated with occurrence and outcome of super-refractory status epilepticus.

    PubMed

    Madžar, Dominik; Knappe, Ruben U; Reindl, Caroline; Giede-Jeppe, Antje; Sprügel, Maximilian I; Beuscher, Vanessa; Gollwitzer, Stephanie; Hamer, Hajo M; Huttner, Hagen B

    2017-11-01

    Super-refractory status epilepticus (SRSE) represents a challenging medical condition with high morbidity and mortality. In this study, we aimed to establish variables related to SRSE development and outcome. We retrospectively screened our databases for refractory SE (RSE) and SRSE episodes between January 2001 and January 2015. Baseline demographics, SE characteristics, and variables reflecting the clinical course were compared in order to identify factors independently associated with SRSE occurrence. Within the SRSE cohort, predictors of in-hospital mortality as well as good functional outcome in survivors to discharge were established through univariate and multivariable analyses. A total of 131 episodes were included, among those 46 (35.1%) meeting the criteria of SRSE. Comparison of RSE and SRSE episodes revealed a lower premorbid mRS score (odds ratio (OR) per mRS point, 0.769; p=0.039) and non-convulsive SE (NCSE) in coma (OR, 4.216; p=0.008) as independent predictors of SRSE. SRSE in-hospital mortality was associated with age (OR, 1.091 per increasing year; p=0.020) and worse premorbid functional status (OR, 1.938 per mRS point; p=0.044). Good functional outcome in survivors was independently related to shorter SRSE duration (OR, 0.714 per day; p=0.038). Better premorbid functional status and NCSE in coma as worst seizure type indicate a role of acute underlying etiologies in the development of SRSE. In-hospital mortality in SRSE is determined by nonmodifiable factors, while functional outcome in survivors depends on seizure duration underscoring the need of achieving rapid seizure termination. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  13. 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

  14. Preoperative therapeutic apheresis for severe medically refractory amiodarone-induced thyrotoxicosis: a case report.

    PubMed

    Yamamoto, Jennifer; Dostmohamed, Hanifa; Schacter, Isanne; Ariano, Robert E; Houston, Donald S; Lewis, Brenda; Knoll, Colleen; Katz, Pamela; Zarychanski, Ryan

    2014-06-01

    Amiodarone is associated with thyroid dysfunction and life-threatening thyrotoxicosis. In medically refractory cases, or where medical therapy is contraindicated, thyroidectomy may be required. To decrease perioperative thyroid storm and to reduce overall surgical risk, apheresis may be considered preoperatively to restore euthyroidism. We report a 46-year-old female with a history of cardiac arrhythmia and tachycardia-induced cardiomyopathy for which she received amiodarone. Months after discontinuation of amiodarone, the patient presented with wide complex tachycardia and symptoms of thyrotoxicosis. Laboratory testing confirmed severe thyrotoxicosis which was subsequently refractory to medical therapy. Total thyroidectomy was required. Following a total of 10 apheresis treatments, thyroid hormone levels were reduced to near normal levels and the patient's symptoms improved. Thyroidectomy was performed without intraoperative or postoperative complication. In the setting of life-threatening, medically refractory amiodarone-induced thyrotoxicosis, therapeutic apheresis can effectively reduce thyroid hormone levels and restore a state of clinical and biochemical euthyroidism. © 2013 Wiley Periodicals, Inc.

  15. 131I therapy for 345 patients with refractory severe hyperthyroidism: Without antithyroid drug pretreatment.

    PubMed

    Ding, Yong; Xing, Jialiu; Fang, Yi; Wang, Yong; Zhang, Youren; Long, Yahong

    2016-02-01

    The aim of this study is to evaluate the safety and long-term results of (131)I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment. From January 2002 to December 2012, 408 patients with refractory severe hyperthyroidism were treated with (131)I alone. Among them, 345 were followed up for 1 to 10 years for physical examination, thyroid function, and thyroid ultrasound. Complete Blood Count (CBC) liver function, electrocardiogram, echocardiogram, and Emission Computed Tomography (ECT) thyroid imaging were performed as indicated. The 345 patients had concomitant conditions including thyrotoxic heart disease, severe liver dysfunction, enlarged thyroid weighing 80 to 400 g, severe cytopenia, and vasculitis. One to two weeks prior to (131)I therapy, all patients were given low-iodine diet. The dose of (131)I therapy was 2.59 to 6.66 MBq (70 to180 µCi) per gram of thyroid with an average of 3.83 ± 0.6 MBq (103.6 ± 16.4 µCi); and the total (131)I activity administrated for the individuals was 111 to 3507.6 MBq (3.0 to 94.8 mCi, mean 444 ± 336.7 MBq (12.0 ± 9.1 mCi)). Out of the 408 patients, 283 were cured, 15 with complete remission, and 47 with incomplete remission. No treatment failure or significant clinical worsening was noted in these patients. Our data indicated that (131)I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment is safe and effective. © 2015 by the Society for Experimental Biology and Medicine.

  16. 131I therapy for 345 patients with refractory severe hyperthyroidism: Without antithyroid drug pretreatment

    PubMed Central

    Xing, Jialiu; Fang, Yi; Wang, Yong; Zhang, Youren; Long, Yahong

    2015-01-01

    The aim of this study is to evaluate the safety and long-term results of 131I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment. From January 2002 to December 2012, 408 patients with refractory severe hyperthyroidism were treated with 131I alone. Among them, 345 were followed up for 1 to 10 years for physical examination, thyroid function, and thyroid ultrasound. Complete Blood Count (CBC) liver function, electrocardiogram, echocardiogram, and Emission Computed Tomography (ECT) thyroid imaging were performed as indicated. The 345 patients had concomitant conditions including thyrotoxic heart disease, severe liver dysfunction, enlarged thyroid weighing 80 to 400 g, severe cytopenia, and vasculitis. One to two weeks prior to 131I therapy, all patients were given low-iodine diet. The dose of 131I therapy was 2.59 to 6.66 MBq (70 to180 µCi) per gram of thyroid with an average of 3.83 ± 0.6 MBq (103.6 ± 16.4 µCi); and the total 131I activity administrated for the individuals was 111 to 3507.6 MBq (3.0 to 94.8 mCi, mean 444 ± 336.7 MBq (12.0 ± 9.1 mCi)). Out of the 408 patients, 283 were cured, 15 with complete remission, and 47 with incomplete remission. No treatment failure or significant clinical worsening was noted in these patients. Our data indicated that 131I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment is safe and effective. PMID:26341470

  17. Induction of burst suppression or coma using intravenous anesthetics in refractory status epilepticus.

    PubMed

    Kang, Bong Su; Jung, Keun-Hwa; Shin, Jeong-Won; Moon, Jang Sup; Byun, Jung-Ick; Lim, Jung-Ah; Moon, Hye Jin; Kim, Young-Soo; Lee, Soon-Tae; Chu, Kon; Lee, Sang Kun

    2015-05-01

    General anesthetic-induced coma therapy has been recommended for the treatment of refractory status epilepticus (RSE). However, the influence of electroencephalographic (EEG) burst suppression (BS) on outcomes still remains unclear. This study investigated the impact of intravenous anesthetic-induced BS on the prognosis of RSE using a retrospective analysis of all consecutive adult patients who received intravenous anesthetic treatment for RSE at the Seoul National University Hospital between January 2006 and June 2011. Twenty-two of the 111 episodes of RSE were enrolled in this study. Of the 22 RSE patients, 12 (54.5%) were women and 18 (81.4%) exhibited generalized convulsive status epilepticus. Sixteen patients (72.7%) were classified as having acute symptomatic etiology, including three patients with anoxic encephalopathy, and others with remote symptomatic etiology. Only two patients (9.1%) had a favorable Status Epilepticus Severity Score (0-2) at admission. All patients received midazolam (MDZ) as a primary intravenous anesthetic drug for RSE treatment; three (13.6%) received MDZ and propofol, and one (4.5%) received MDZ and pentobarbital. The rates of mortality and poor outcome at discharge were 13.6% (n=3) and 54.5% (n=12), respectively. While BS was achieved in six (27.5%) patients, it was not associated with mortality or poor outcome. Induced BS was associated with prolonged hospital stay in subgroup analysis when excluding anoxic encephalopathy. Our results suggest that induction of BS for treating RSE did not affect mortality or outcome at discharge and may lead to an increased length of hospital stay. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Mega-dose phenobarbital therapy for super-refractory status epilepticus.

    PubMed

    Byun, Jung-Ick; Chu, Kon; Sunwoo, Jun-Sang; Moon, Jangsup; Kim, Tae-Joon; Lim, Jung-Ah; Jun, Jin-Sun; Lee, Han Sang; Lee, Woo-Jin; Lee, Doo Young; Jeon, Daejong; Lee, Soon-Tae; Jung, Keun-Hwa; Jung, Ki-Young; Lee, Sang Kun

    2015-12-01

    To evaluate the efficacy and safety of mega-dose phenobarbital (MDPB; enteral or parenteral phenobarbital >10 mg/kg/day) for treating super-refractory status epilepticus (SRSE; continuous or recurrent status epilepticus for ≥24 hours after the onset of continuous anaesthetic treatment) in adult patients. Adult patients with SRSE who were treated with MDPB in our institution from March 2005 to September 2014 were reviewed. We collected data on basic demographics, clinical features, functional status, anticonvulsant treatment, and possible adverse events. SRSE outcome was divided into six categories: successful therapy, initial failure, breakthrough seizures, withdrawal seizures, intolerable side effects, and death during treatment. Ten adult patients with SRSE received MDPB. Median age at seizure onset was 38 years (range: 18-59), and half were male. All patients had no history of seizures and had symptoms suggestive of viral encephalitis. Median duration of status epilepticus was 17.5 days (range: 6-60) and anaesthetics were used for a median of 14.0 days (range: 2-54) before MDPB. Successful control of SRSE was achieved in half of the patients, however, only one of ten patients was able to fully recover at discharge. Median duration of the MDPB was 45.5 days and the maximum serum phenobarbital level reached a median of 151.5 μg/ml. Patients with successful MDPB therapy had normal brain imaging (80% vs. 0%; p=0.048) and better functional outcome at discharge and after three months of follow-up. Infection was the most critical complication, along with cardiorespiratory depression. MDPB is a therapeutic option for control of SRSE when other choices are exhausted.

  19. Efficacy of lacosamide in children and adolescents with drug-resistant epilepsy and refractory status epilepticus: A systematic review.

    PubMed

    Ortiz de la Rosa, Johann Sebastián; Ladino, Lady Diana; Rodríguez, Paula Juliana; Rueda, María Camila; Polanía, Juan Pablo; Castañeda, Angie Catalina

    2018-03-01

    Lacosamide, is one of the newer antiepileptic drug approved for focal drug-resistant epilepsy as an add-on treatment in patients older than 16 years. However, there is growing evidence of its use, safety and efficacy in children. We aim to evaluate efficacy and tolerability of lacosamide in focal and generalized drug-resistant epilepsy and refractory status epilepticus in the pediatric population. We conducted a systematic review on MEDLINE, EMBASE, COCHRANE, Google Scholar and Scielo from January 2008 to January 2017. The primary outcome was the efficacy of lacosamide in children with drug-resistant epilepsy and refractory status epilepticus. Efficacy and adverse events attributed to lacosamide were extracted from each publication and systematically reported. We performed no meta-analyses due to limited available data. Of 175 abstracts identified by the search, 82 were reviewed as full-text. Twenty-six articles fulfilled eligibility criteria and described outcomes in 797 patients (57% male). The majority of studies were retrospective (69%) small series (84%). On average 51% of patients had 50% or greater seizure reduction. The mean seizure freedom rate was 24%. Adverse effects occurred in 18-59% of patients. The main events were dizziness, sedation, gastrointestinal upset, mood and behavioral changes. Half of the patients with Lennox Gastaut syndrome showed 50% or greater seizure reduction, 32% did not response to lacosamide and 17% suffered seizure aggravation. Current evidence shows lacosamide as a good option in pediatric patients with focal drug-resistant epilepsy and refractory status epilepticus as an add-on therapy given its efficacy on seizure control and safety profile. The use of lacosamide in Lennox-Gastaut syndrome shows conflicting data. Large randomized controlled studies in the pediatric population are necessary to substantiate these findings. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  20. Brexanolone as adjunctive therapy in super‐refractory status epilepticus

    PubMed Central

    Claassen, Jan; Wainwright, Mark S.; Husain, Aatif M.; Vaitkevicius, Henrikas; Raines, Shane; Hoffmann, Ethan; Colquhoun, Helen; Doherty, James J.; Kanes, Stephen J.

    2017-01-01

    Objective Super‐refractory status epilepticus (SRSE) is a life‐threatening form of status epilepticus that continues or recurs despite 24 hours or more of anesthetic treatment. We conducted a multicenter, phase 1/2 study in SRSE patients to evaluate the safety and tolerability of brexanolone (USAN; formerly SAGE‐547 Injection), a proprietary, aqueous formulation of the neuroactive steroid, allopregnanolone. Secondary objectives included pharmacokinetic assessment and open‐label evaluation of brexanolone response during and after anesthetic third‐line agent (TLA) weaning. Methods Patients receiving TLAs for SRSE control were eligible for open‐label, 1‐hour brexanolone loading infusions, followed by maintenance infusion. After 48 hours of brexanolone infusion, TLAs were weaned during brexanolone maintenance. After 4 days, the brexanolone dose was tapered. Safety and functional status were assessed over 3 weeks of follow‐up. Results Twenty‐five patients received open‐label study drug. No serious adverse events (SAEs) were attributable to study drug, as determined by the Safety Review Committee. Sixteen patients (64%) experienced ≥1 SAE. Six patient deaths occurred, all deemed related to underlying medical conditions. Twenty‐two patients underwent ≥1 TLA wean attempt. Seventeen (77%) met the response endpoint of weaning successfully off TLAs before tapering brexanolone. Sixteen (73%) were successfully weaned off TLAs within 5 days of initiating brexanolone infusion without anesthetic agent reinstatement in the following 24 hours. Interpretation In an open‐label cohort of limited size, brexanolone demonstrated tolerability among SRSE patients of heterogeneous etiologies and was associated with a high rate of successful TLA weaning. The results suggest the possible development of brexanolone as an adjunctive therapy for SRSE requiring pharmacological coma for seizure control. Ann Neurol 2017;82:342–352 PMID:28779545

  1. Refractory status epilepticus after inadvertent intrathecal injection of tranexamic acid treated by magnesium sulfate.

    PubMed

    Hatch, D M; Atito-Narh, E; Herschmiller, E J; Olufolabi, A J; Owen, M D

    2016-05-01

    We present a case of accidental injection of tranexamic acid during spinal anesthesia for an elective cesarean delivery. Immediately following intrathecal injection of 2mL of solution, the patient complained of severe back pain, followed by muscle spasm and tetany. As there was no evidence of spinal block, the medications given were checked and a 'used' ampoule of tranexamic acid was found on the spinal tray. General anesthesia was induced but muscle spasm and tetany persisted despite administration of a non-depolarizing muscle relaxant. Hemodynamic instability, ventricular tachycardia, and status epilepticus developed, which were refractory to phenytoin, diazepam, and infusions of thiopental, midazolam and amiodarone. Magnesium sulfate was administered postoperatively in the intensive care unit, following which the frequency of seizures decreased, eventually stopping. Unfortunately, on postoperative day three the patient died from cardiopulmonary arrest after an oxygen supply failure that was not associated with the initial event. This report underlines the importance of double-checking medications before injection in order to avoid a drug error. As well, it suggests that magnesium sulfate may be useful in stopping seizures caused by the intrathecal injection of tranexamic acid. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Successful treatment of severe pouchitis with rebamipide refractory to antibiotics and corticosteroids: A case report

    PubMed Central

    Miyata, Mitsuki; Konagaya, Toshihiro; Kakumu, Shiniti; Mori, Takeshi

    2006-01-01

    The antibiotics, metronidazole and ciprofloxacin, are the first-line treatment for pouchitis. Patients who do not respond to antibiotics or conventional medications represent a major challenge to therapy. In this report, we have described a successful treatment of severe refractory pouchitis with a novel agent, rebamipide, known to promote epithelial cell regeneration and angiogenesis. A 27-year-old male with ileo-anal pouch surgery presented with worsening anal pain, diarrhea, and abdominal pain. The patient was diagnosed to have pouchitis and was given metronidazole together with betamethasone enema (3.95 mg/dose). However, despite this intensive therapy, the patient did not improve. On endoscopy, ulceration and inflammation were seen in the ileal pouch together with contact bleeding and mucous discharge. The patient was treated with rebamipide enema (150 mg/dose) twice a day for 8 wk without additional drug therapy. Two weeks after the rebamipide therapy, stool frequency started to decrease and fecal hemoglobin became negative at the 4th wk. At the end of the therapy, endoscopy revealed that ulcers in the ileal pouch had healed with no obvious inflammation. The effect of rebamipide enema was dramatic and was maintained throughout the 11-mo follow-up. The patient continued to be in remission. No adverse effects were observed during the treatment or the follow-up period. The sustained response seen in this case with severe and refractory pouchitis indicates that agents, which promote epithelial cell growth, angiogenesis and mucosal tissue regeneration, are potential therapeutic agents for the treatment of refractory colorectal lesions. PMID:16489687

  3. 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.

  4. Costs, length of stay, and mortality of super-refractory status epilepticus: A population-based study from Germany.

    PubMed

    Strzelczyk, Adam; Ansorge, Sonja; Hapfelmeier, Jana; Bonthapally, Vijayveer; Erder, M Haim; Rosenow, Felix

    2017-09-01

    Super-refractory status epilepticus (SRSE) is a severe condition in which a patient in status epilepticus (SE) for ≥24 h does not respond to first-, second-, or third-line therapy. The economic impact of SRSE treatment remains unclear. A health insurance research database was used for a population-based estimation of SRSE-associated inpatient costs, length of stay, and mortality in Germany. An algorithm using International Classification of Diseases, 10th Edition coding and treatment parameters identified and classified patients in a German statutory health insurance database covering admissions from 2008 to 2013 as having refractory SE (RSE) or SRSE. Admissions data in our study refer to these classifications. Associated patient data included costs, procedures, and demographics. The algorithm identified 2,585 (all type) SE admissions, classified as 1,655 nonrefractory SE (64%), 592 (22.9%) RSE, and 338 (13.1%) SRSE, producing database incidence rates of 15.0 in 100,000, 5.2 in 100,000, and 3.0 in 100,000 per year, respectively. Median cost per admission was €4,063 for nonrefractory SE, €4,581 (p < 0.001) for RSE, and €32,706 (p < 0.001) for SRSE. Median length of stay varied significantly between 8 days (mean = 13.6) in nonrefractory SE, 14 days in RSE, and up to 37 days in SRSE. Discharge mortality increased from 9.6% in nonrefractory SE to 15.0% (p < 0.001) in RSE and 39.9% (p < 0.001) in SRSE. This study evaluated the hospital treatment costs associated with admissions classified by the algorithm as SRSE in Germany. SRSE represented 13% of all SE admissions, but resulted in 56% of all SE-related costs. The lack of approved treatments and limited number of evidence-based treatment guidelines highlight the need for further evaluations of the SRSE burden of illness and the potential for further optimization of treatments for SRSE. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  5. Predictors of outcomes and refractoriness in status epilepticus: A prospective study.

    PubMed

    Atmaca, Murat Mert; Bebek, Nerses; Baykan, Betül; Gökyiğit, Ayşen; Gürses, Candan

    2017-10-01

    The objective of this study was to determine the predictors of outcomes and refractoriness in status epilepticus (SE). This is a prospective study of 59 adult patients with SE who were admitted to the Emergency Department between February 2012 and December 2013. The effects of clinical, demographic, and electrophysiologic features of patients with SE were evaluated. To evaluate outcome in SE, STESS, mSTESS, and EMSE scales were used. Logistic regression analysis showed that being aged ≥65years (p=0.02, OR: 17.68, 95% CI: [1.6-198.4]) for the short term and having potentially fatal etiology (p=0.027, OR: 11.7, 95% CI: [1.3-103]) for the long term were the only independent predictors of poor outcomes; whereas, the presence of periodic epileptiform discharges (PEDs) in EEG was the only independent predictor of refractoriness (p=0.032, OR: 13.7, 95% CI: [1.3-148.5]). The patients with ≥3 Status Epilepticus Severity Score (STESS) did not have poorer outcomes in the short- (p=0.157) and long term (p=0.065). There was no difference between patients with 0-2, 3-4, and ≥4 mSTESS in the short- and long term in terms of outcome (p=0.28 and 0.063, respectively). Also, there was no difference between subgroups (convulsive SE [CSE], nonconvulsive SE [NCSE], and epilepsia partialis continua [EPC]) in terms of STESS and mSTESS. When patients with EPC were excluded, both STESS and mSTESS scores of the patients correlated with poorer long-term outcomes (p=0.025 and 0.017, respectively). The patients with ≥64 points in the Epidemiology-based Mortality in SE-Etiology, age, comorbidity, EEG (EMSE-EACE) score and those with ≥27 points in EMSE-Etiology, age, comorbidity (EMSE-EAC) score did not have poorer outcomes in the short term (p=0.06 and 0.274, respectively) while they had significantly poorer outcome in the long term (p<0.001 and 0.002, respectively). In subgroup analysis, patients with CSE with ≥64 points in EMSE-EACE had significantly poorer outcome in the both

  6. Drug-Refractory Aggression, Self-Injurious Behavior, and Severe Tantrums in Autism Spectrum Disorders: A Chart Review Study

    ERIC Educational Resources Information Center

    Adler, Benjamin A.; Wink, Logan K.; Early, Maureen; Shaffer, Rebecca; Minshawi, Noha; McDougle, Christopher J.; Erickson, Craig A.

    2015-01-01

    Aggression, self-injurious behavior, and severe tantrums are impairing symptoms frequently experienced by individuals with autism spectrum disorders. Despite US Food and Drug Administration approval of two atypical antipsychotics targeting these symptoms in youth with autistic disorder, they remain frequently drug refractory. We define…

  7. Treatment responsive GABA(B)-receptor limbic encephalitis presenting as new-onset super-refractory status epilepticus (NORSE) in a deployed U.S. soldier.

    PubMed

    Hainsworth, Jeffrey Brian; Shishido, Akira; Theeler, Brett James; Carroll, Craig Grason; Fasano, Rebecca Ellen

    2014-12-01

    A 23-year-old, previously healthy, deployed U.S. soldier presented with bilateral temporal lobe seizures recalcitrant to multiple antiepileptic drugs and anti-seizure anaesthetic agents. He received methylprednisolone, intravenous immunoglobulins, plasma exchange, and rituximab for presumed autoimmune encephalitis before achieving seizure freedom. Six weeks after presentation, the aetiology of his refractory seizures was found to be due to autoantibodies targeting the anti-GABA(B)-receptor. This case is noteworthy for being the first reported case of anti-GABA(B)-receptor limbic encephalitis presenting with new-onset refractory status epilepticus (NORSE), a clinical syndrome that often carries a grave prognosis and in which a treatable aetiology is often never discovered. Our case also supports testing for GABA-receptor autoantibodies and the upfront use of multi-modal immunotherapy in patients presenting with limbic encephalitis and new refractory seizures.

  8. 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.

  9. Treatment of Established Status Epilepticus.

    PubMed

    Falco-Walter, Jessica J; Bleck, Thomas

    2016-04-25

    Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE)) is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT). Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus), elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE.

  10. Long-term outcome of refractory status epilepticus in adults: A retrospective population-based study.

    PubMed

    Kantanen, Anne-Mari; Reinikainen, Matti; Parviainen, Ilkka; Kälviäinen, Reetta

    2017-07-01

    Refractory status epilepticus (RSE) is a neurological emergency with significant morbidity and mortality. We aimed to analyze the long-term outcome of intensive care unit (ICU)-treated RSE and super-refractory status epilepticus (SRSE) patients in a population based cohort. A retrospective study of ICU- and anesthesia-treated RSE patients in Kuopio University Hospital's (KUH) special responsibility area hospitals in the central and eastern part of Finland from Jan. 1, 2010 to Dec. 31, 2012 was conducted. KUH's catchment area consists of five hospitals-one university hospital and four central hospitals-and covers a population of 840 000. We included all consecutive adult (16 years or older) RSE patients admitted in the participating ICUs during the 3-year period and excluded patients with postanoxic etiologies. We used a modified Rankin Scale (mRS) as a long-term (1-year) outcome measure: good (mRS 0-3, recovered to baseline function) or poor (mRS 4-6, major functional deficit or death). We identified 75 patients with ICU- and anesthesia-treated RSE, corresponding to an annual incidence of 3.0 (95% confidence interval (CI) 2.4-3.8). 21% of the patients were classified as SRSE, with the annual incidence being 0.6/100 000 (95% CI 0.4-1.0). For RSE, the ICU mortality was 0%, hospital mortality was 7% (95% CI 1.2%-12.8%) (n=5), and one-year mortality was 23% (CI 95% 13.4%-32.5%) (n=17). 48% (n=36) of RSE patients recovered to baseline, and 29% (n=22) showed neurological deficit at 1year. Poor outcome (mRS 4-6) was recorded for 52% (n=39) of the patients. Older age was associated with poorer outcome at 1year (p=0.03). For SRSE, hospital mortality was 6% (n=1) and 1-year mortality was 19% (n=3) (95%CI 0%-38.2%). During 1-year follow-up, nearly 50% of the ICU-treated RSE patients recovered to baseline function, whereas 30% showed new functional defects and 20% died. SRSE does not have a necessarily poorer outcome. The outcome is worse in older patients and in patients with

  11. 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.

  12. Refractory status epilepticus in children with and without prior epilepsy or status epilepticus

    PubMed Central

    Sánchez Fernández, Iván; Jackson, Michele C.; Abend, Nicholas S.; Arya, Ravindra; Brenton, James N.; Carpenter, Jessica L.; Chapman, Kevin E.; Gaillard, William D.; Gaínza-Lein, Marina; Glauser, Tracy A.; Goldstein, Joshua L.; Goodkin, Howard P.; Helseth, Ashley; Kapur, Kush; McDonough, Tiffani L.; Mikati, Mohamad A.; Peariso, Katrina; Riviello, James; Tasker, Robert C.; Topjian, Alexis A.; Wainwright, Mark S.; Wilfong, Angus; Williams, Korwyn

    2017-01-01

    Objective: To compare refractory convulsive status epilepticus (rSE) management and outcome in children with and without a prior diagnosis of epilepsy and with and without a history of status epilepticus (SE). Methods: This was a prospective observational descriptive study performed from June 2011 to May 2016 on pediatric patients (1 month–21 years of age) with rSE. Results: We enrolled 189 participants (53% male) with a median (25th–75th percentile) age of 4.2 (1.3–9.6) years. Eighty-nine (47%) patients had a prior diagnosis of epilepsy. Thirty-four (18%) patients had a history of SE. The time to the first benzodiazepine was similar in participants with and without a diagnosis of epilepsy (15 [5–60] vs 16.5 [5–42.75] minutes, p = 0.858). Patients with a diagnosis of epilepsy received their first non-benzodiazepine (BZD) antiepileptic drug (AED) later (93 [46–190] vs 50.5 [28–116] minutes, p = 0.002) and were less likely to receive at least one continuous infusion (35/89 [39.3%] vs 57/100 [57%], p = 0.03). Compared to patients with no history of SE, patients with a history of SE received their first BZD earlier (8 [3.5–22.3] vs 20 [5–60] minutes, p = 0.0073), although they had a similar time to first non-BZD AED (76.5 [45.3–124] vs 65 [32.5–156] minutes, p = 0.749). Differences were mostly driven by the patients with an out-of-hospital rSE onset. Conclusions: Our study establishes that children with rSE do not receive more timely treatment if they have a prior diagnosis of epilepsy; however, a history of SE is associated with more timely administration of abortive medication. PMID:28011930

  13. Refractory status epilepticus in children with and without prior epilepsy or status epilepticus.

    PubMed

    Sánchez Fernández, Iván; Jackson, Michele C; Abend, Nicholas S; Arya, Ravindra; Brenton, James N; Carpenter, Jessica L; Chapman, Kevin E; Gaillard, William D; Gaínza-Lein, Marina; Glauser, Tracy A; Goldstein, Joshua L; Goodkin, Howard P; Helseth, Ashley; Kapur, Kush; McDonough, Tiffani L; Mikati, Mohamad A; Peariso, Katrina; Riviello, James; Tasker, Robert C; Topjian, Alexis A; Wainwright, Mark S; Wilfong, Angus; Williams, Korwyn; Loddenkemper, Tobias

    2017-01-24

    To compare refractory convulsive status epilepticus (rSE) management and outcome in children with and without a prior diagnosis of epilepsy and with and without a history of status epilepticus (SE). This was a prospective observational descriptive study performed from June 2011 to May 2016 on pediatric patients (1 month-21 years of age) with rSE. We enrolled 189 participants (53% male) with a median (25th-75th percentile) age of 4.2 (1.3-9.6) years. Eighty-nine (47%) patients had a prior diagnosis of epilepsy. Thirty-four (18%) patients had a history of SE. The time to the first benzodiazepine was similar in participants with and without a diagnosis of epilepsy (15 [5-60] vs 16.5 [5-42.75] minutes, p = 0.858). Patients with a diagnosis of epilepsy received their first non-benzodiazepine (BZD) antiepileptic drug (AED) later (93 [46-190] vs 50.5 [28-116] minutes, p = 0.002) and were less likely to receive at least one continuous infusion (35/89 [39.3%] vs 57/100 [57%], p = 0.03). Compared to patients with no history of SE, patients with a history of SE received their first BZD earlier (8 [3.5-22.3] vs 20 [5-60] minutes, p = 0.0073), although they had a similar time to first non-BZD AED (76.5 [45.3-124] vs 65 [32.5-156] minutes, p = 0.749). Differences were mostly driven by the patients with an out-of-hospital rSE onset. Our study establishes that children with rSE do not receive more timely treatment if they have a prior diagnosis of epilepsy; however, a history of SE is associated with more timely administration of abortive medication. © 2016 American Academy of Neurology.

  14. Super-refractory nonconvulsive status epilepticus secondary to fat embolism: A clinical, electrophysiological, and pathological study.

    PubMed

    Fernández-Torre, José L; Burgueño, Paula; Ballesteros, María A; Hernández-Hernández, Miguel A; Villagrá-Terán, Nuria; de Lucas, Enrique Marco

    2015-08-01

    Fat embolism syndrome (FES) is a rare complication of long-bone fractures and joint reconstruction surgery. To the best of our knowledge, we describe the clinical, electrophysiological, neuroimaging, and neuropathological features of the first case of super-refractory nonconvulsive status epilepticus (sr-NCSE) secondary to fat embolism. An 82-year-old woman was transferred to our intensive care unit because of a sudden decrease of consciousness level, right hemiparesis, and acute respiratory failure in the early postoperative period of knee prosthesis surgery. Brain computed tomography (TC) including angio-CT and CT perfusion was normal. An urgent video-electroencephalography (v-EEG) evaluation showed continuous sharp-and slow-wave at 2.0-2.5 Hz in keeping with the diagnosis of generalized NCSE. Epileptiform discharges ceased after the administration of 5mg of intravenous diazepam, and background activity constituted by diffuse theta waves was observed without clinical improvement. Treatment with levetiracetam (1000 mg/day) and sedation with propofol and midazolam were initiated. Moreover, continuous v-EEG monitoring was also started. Despite antiepileptic therapy, epileptiform activity recurred after the interruption of profound sedation, and valproate and lacosamide were added during the ensuing days. Magnetic resonance imaging (MRI) disclosed small scattered foci of acute ischemic infarcts and diffuse petechiae involving the basal ganglia and pons and centrum semiovale in keeping with fat embolism. Super-refractory nonconvulsive status epilepticus remained without control for 2 weeks. Finally, the patient died. The clinical autopsy revealed a bilateral lung fat embolism associated with a hemorrhagic infarction in the left lower lobe. Fatty lesions were also seen in the intestine and pancreas. Scattered microscopic cerebral infarcts associated with fat emboli in the capillaries were noticed, affecting both supra- and infratentorial structures. In addition

  15. Extracorporeal Membrane Oxygenation for Refractory Severe Respiratory Failure in Acute Interstitial Pneumonia.

    PubMed

    Gonçalves-Venade, Gabriela; Lacerda-Príncipe, Nuno; Roncon-Albuquerque, Roberto; Paiva, José Artur

    2018-05-01

    Acute interstitial pneumonia (AIP) is a rare idiopathic interstitial lung disease with rapid progressive respiratory failure and high mortality. In the present report, three cases of AIP complicated by refractory respiratory failure supported with extracorporeal membrane oxygenation (ECMO) are presented. One male and two female patients (ages 27-59) were included. Venovenous ECMO support was provided using miniaturized systems, with two-site femoro-jugular circuit configuration. Despite lung protective ventilation, prone position and neuromuscular blockade, refractory respiratory failure of unknown etiology supervened (ratio of arterial oxygen partial pressure to fractional inspired oxygen 46-130) and ECMO was initiated after 3-7 days of mechanical ventilation. AIP diagnosis was established after exclusion of infectious and noninfectious acute respiratory distress syndrome on the basis of clinical and analytical data, bronchoalveolar lavage analysis and lung imaging, with a confirmatory surgical lung biopsy revealing diffuse alveolar damage of unknown etiology. Immunosuppressive treatment consisted in high-dose corticosteroids and cyclophosphamide in one case. Two patients survived to hospital discharge. ECMO allowed AIP diagnosis and treatment in the presence of refractory respiratory failure, therefore reducing ventilator-induced lung injury and bridging lung recovery in two patients. ECMO referral should be considered in refractory respiratory failure if AIP is suspected. © 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  16. Refractory Convulsive Status Epilepticus in Children: Etiology, Associated Risk Factors and Outcome

    PubMed Central

    BARZEGAR, Mohammad; MAHDAVI, Mohammad; GALEGOLAB BEHBEHANI, Afshin; TABRIZI, Aidin

    2015-01-01

    Objective Refractory status epilepticus (RSE) is a life-threatening disease in children wherein the patient’s convulsive seizures do not respond to adequate initial anticonvulsants. RSE is associated with high rate of mortality and morbidity. This study was aimed to survey the risk factors leading status epilepticus (SE) to RSE in children, and their early outcome. Materials & Methods Patients with SE hospitalized in Tabriz Children’s Hospital, Iran were studied during the years 2007 and 2008 with regard to their clinical profile, etiology, the treatment methods available to them and their outcome upon release from the hospital. Results Among 132 patients with SE, 53 patients (40.15%) suffered from RSE. Acute symptomatic etiology was a risk factor responsible for developing RSE in the patient (P=0.004). Encephalitis was the most common etiology of acute symptomatic SE. There was no significant relationship observed between RSE and the patients’ age, gender, date of initial drug intake and type of seizure. The mortality rate was 8.3% and a new neurological deficit occurred in 25.7% of cases. None of RSE with encephalitis returned to the baseline status. Mortality and morbidity rates were significantly higher in children with RSE than in those with SE (P=0.006). Conclusion Etiology of SE significantly influenced prognosis of it with significant incidence of RSE in acute symptomatic group. Because acute neurological insult such as encephalitis and meningitis are common causes of RSE in children, properly management of them is necessary to avoid permanent brain damage. PMID:26664438

  17. Treatment of Established Status Epilepticus

    PubMed Central

    Falco-Walter, Jessica J.; Bleck, Thomas

    2016-01-01

    Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE)) is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT). Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus), elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE. PMID:27120626

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

    PubMed

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

    2015-02-01

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

  19. Propofol versus thiopental sodium for the treatment of refractory status epilepticus.

    PubMed

    Prabhakar, Hemanshu; Kalaivani, Mani

    2017-02-03

    This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 6, 2015).Failure to respond to antiepileptic drugs in patients with uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is a substantial lack of evidence as to which of the two drugs is better in terms of clinical outcomes. To compare the efficacy, adverse effects, and short- and long-term outcomes of refractory status epilepticus (RSE) treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (16 August 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 16 August 2016), MEDLINE (Ovid, 1946 to 16 August 2016), ClinicalTrials.gov (16 August 2016), and the South Asian Database of Controlled Clinical Trials (16 August 2016). Previously we searched IndMED, but this was not accessible at the time of the latest update. All randomised controlled trials (RCTs) or quasi-RCTs (regardless of blinding) assessing the control of RSE using either thiopental sodium or propofol in patients of any age and gender. Two review authors screened the search results and reviewed the abstracts of relevant and eligible trials before retrieving the full-text publications. One study with a total of 24 participants was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE receiving either propofol or thiopental sodium for the control of seizure activity. This study was terminated early due to recruitment problems. For our primary outcome of total control of seizures after the first course of study drug, there were 6

  20. 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.

  1. 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.

  2. 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.

  3. Medical nutrition therapy is the essential cornerstone for effective treatment of "refractory" severe hypertriglyceridemia regardless of pharmaceutical treatment: Evidence from a Lipid Management Program.

    PubMed

    Rhodes, Katherine S; Weintraub, Martha; Marchlewicz, Elizabeth H; Rubenfire, Melvyn; Brook, Robert D

    2015-01-01

    Patients with refractory severe hypertriglyceridemia are at risk of pancreatitis and cardiovascular disease. The role of individualized nutrition therapy in these patients independent of pharmaceutical treatment has not been documented. To document the effect of nutrition intervention on severe hypertriglyceridemia regardless of medication status or prior nutrition counseling. Outcomes of new patients with triglycerides ≥ 500 mg/dL presenting to a Lipid Management Program over a 6-year period were tracked. Patients received comprehensive laboratory assessment, nutrition assessment, and initiation of an individualized diet intervention before seeing the lipidologist. Clinical and behavioral outcomes were recorded. In all, 168 patients (117 men; mean age, 49.03 ± 11.22 years; body mass index, 32.61 ± 5.85 kg/m(2); 110 (65.5%) on lipid-lowering medications) returned for assessment of nutrition intervention. Triglycerides were reduced from median (interquartile range) 961.5 (611.5-1785.3) to 493.0 (337-736.3) mg/dL (P < .0001 for log transformation of triglycerides). There was no difference in median percentage reduction in triglycerides after nutrition intervention between those not on lipid-lowering medication, on a fibric acid derivative, on other lipid-lowering medication, or on a combination of lipid-lowering medications (P = .376) in a median (interquartile range) of 5 (3-7) weeks. Effect was independent of prior nutrition counseling (P = .260). Reported percentage fat in the diet at second visit correlated with log-transformed triglycerides achieved, independent of initial triglycerides level (r = 0.290; P = .001). Individualized nutrition therapy results in changes in eating behavior and reductions in triglyceride levels in patients with refractory severe hypertriglyceridemia independent of lipid-lowering medication(s) and prior nutrition counseling. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  4. Systematic Review and Meta-Analysis: Infliximab or Cyclosporine as Rescue Therapy in Patients With Severe Ulcerative Colitis Refractory to Steroids.

    PubMed

    Narula, Neeraj; Marshall, John K; Colombel, Jean-Frederic; Leontiadis, Grigorios I; Williams, John G; Muqtadir, Zack; Reinisch, Walter

    2016-04-01

    Acute severe steroid-refractory ulcerative colitis (UC) carries a poor prognosis and requires optimal management. A systematic review and meta-analysis were conducted to assess cyclosporine and infliximab (IFX) as rescue agents in patients with steroid-refractory UC. A literature search identified studies that investigated IFX and cyclosporine in steroid-refractory UC patients. The primary outcome was short-term response to treatment. Secondary outcomes included the rates of colectomy at 3 months and 12 months, adverse drug reactions, post-operative complications in those who received rescue therapy but underwent colectomy subsequently, and mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) are reported. Overall, 16 studies with 1,473 participants were eligible for inclusion. Among three randomized controlled trials, no significant difference was seen with IFX compared with cyclosporine with regard to treatment response and 3- or 12-month colectomy. Among 13 non-randomized studies, IFX was associated with significantly higher rates of treatment response (OR 2.96 (95% CI 2.12-4.14, χ(2)=6.50, I(2)=0%)) and a lower 12-month colectomy rate (OR 0.42 (95% CI 0.22-0.83, χ(2)=30.94, I(2)=71%)), with no significant difference seen in the 3-month colectomy rate (OR 0.53 (95% CI 0.22-1.28, χ(2)=22.73, I(2)=69%)) compared with cyclosporine. There were no significant differences between IFX and cyclosporine in adverse drug-related events, post-operative complications, or mortality. In the management of steroid-refractory severe UC, no definitive difference between IFX and cyclosporine is demonstrated by randomized trials, but non-randomized studies suggest that IFX is associated with better treatment response and lower risk of colectomy at 12 months. Prospective studies comparing dose-optimized IFX with cyclosporine are needed.

  5. 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.

  6. A Case of Severe, Prolonged, Refractory Hypophosphatemia After Zoledronic Acid Administration.

    PubMed

    Clark, Sarah L; Nystrom, Erin M

    2016-04-01

    Zoledronic acid (ZA) administration has been associated with electrolyte abnormalities, including hypocalcemia, hypomagnesemia, hypokalemia, and hypophosphatemia. We describe a case of severe, refractory hypophosphatemia in a patient who received ZA for hypercalcemia of malignancy (HCM). Little data are available that describe the incidence or degree of severity of hypophosphatemia that can occur following ZA administration. In addition, no formal recommendations exist to guide monitoring for or management of electrolyte derangements in the setting of bisphosphonate use. Our patient required daily, high-dose phosphorus replacement beginning day 4 following ZA administration. The average daily dose of phosphorus, including both intravenous and enteral administration, was highest in the first 2 weeks after ZA, averaging 77 mmol/d days 4 through 15, and does not include sources of phosphorus from the patient's nutrition support. Despite this high amount of supplementation, which was well beyond what meets normal daily requirements and the amount expected to treat "usual" hypophosphatemia, the patient did not achieve sustained normal serum phosphorus levels for over 30 days after ZA. ZA is a favorable option for treating HCM because of its longer duration of action, potent serum calcium-lowering effects, and favorable safety profile. The risk of hypophosphatemia with ZA use is reviewed. © The Author(s) 2016.

  7. 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.

  8. 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.

  9. 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.

  10. Efficacy of anti-TNF alpha in severe and/or refractory Behçet's disease: Multicenter study of 124 patients.

    PubMed

    Vallet, H; Riviere, S; Sanna, A; Deroux, A; Moulis, G; Addimanda, O; Salvarani, C; Lambert, M; Bielefeld, P; Seve, P; Sibilia, J; Pasquali, Jl; Fraison, Jb; Marie, I; Perard, L; Bouillet, L; Cohen, F; Sene, D; Schoindre, Y; Lidove, O; Le Hoang, P; Hachulla, E; Fain, O; Mariette, X; Papo, T; Wechsler, B; Bodaghi, B; Rigon, M Resche; Cacoub, P; Saadoun, D

    2015-08-01

    To report the efficacy and safety of anti-TNF agents in patients with severe and/or refractory manifestations of Behçet's disease (BD). We performed a multicenter study of main characteristics and outcomes of anti-TNF alpha treatments [mainly infliximab (62%), and adalimumab (30%)] in 124 BD patients [48% of men; median age of 33.5 (28-40) years]. Overall response (i.e. complete and partial) rate was 90.4%. Clinical responses were observed in 96.3%, 88%, 70%, 77.8%, 92.3% and 66.7% of patients with severe and/or refractory ocular, mucocutaneous, joint, gastro-intestinal manifestations, central nervous system manifestations and cardiovascular manifestations, respectively. No significant difference was found with respect to the efficacy of anti-TNF used as monotherapy or in association with an immunosuppressive agent. The incidence of BD flares/patient/year was significantly lower during anti-TNF treatment (0.2 ± 0.5 vs 1.7 ± 2.4 before the use of anti-TNF, p < 0.0001). The prednisone dose was significantly reduced at 6 and 12 months (p < 0.0001). In multivariate analysis, retinal vasculitis was negatively associated with complete response to anti-TNF (OR = 0.33 [0.12-0.89]; p = 0.03). The efficacy and relapse free survival were similar regardless of the type of anti-TNF agent used. After a median follow-up of 21 [7-36] months, side effects were reported in 28% of patients, including infections (16.3%) and hypersensitivity reactions (4.1%). Serious adverse events were reported in 13% of cases. Anti-TNF alpha therapy is efficient in all severe and refractory BD manifestations. Efficacy appears to be similar regardless of the anti-TNF agent used (infliximab or adalimumab). Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Management of refractory epilepsy.

    PubMed

    Muñana, Karen R

    2013-05-01

    The term refractory epilepsy is utilized in veterinary medicine to describe a condition in which an animal with epilepsy fails to attain satisfactory seizure control or suffers intolerable side effects despite appropriate therapy with conventional antiepileptic drugs. Refractory epilepsy is an important problem in small animal practice as it occurs in approximately one-third of dogs with epilepsy. Consequently, there is much interest in identifying ways to more effectively treat this population of animals. More than a dozen new antiepileptic drugs have been approved for humans over the last 2 decades, and several of these drugs, including gabapentin, zonisamide, levetiracetam, and pregabalin, have been evaluated for the treatment of refractory seizures in veterinary patients. Nonmedical methods to treat poorly controlled epilepsy are also being explored. The 2 alternative forms of therapy that have shown the most promise in humans with epilepsy are electrical stimulation of the brain and dietary modification, both of which have also been evaluated in dogs. This overview summarizes the available data on pharmacologic as well as nonmedical treatment options for dogs and cats with refractory epilepsy. Although many forms of therapy are currently being utilized in clinical practice, our knowledge of the safety and efficacy of these treatments is limited. Additional randomized controlled trials are needed to better evaluate these novel therapies for refractory epilepsy in dogs and cats. © 2013 Elsevier Inc. All rights reserved.

  12. Abatacept in the treatment of severe, longstanding, and refractory uveitis associated with juvenile idiopathic arthritis.

    PubMed

    Tappeiner, Christoph; Miserocchi, Elisabetta; Bodaghi, Bahram; Kotaniemi, Kaisu; Mackensen, Friederike; Gerloni, Valeria; Quartier, Pierre; Lutz, Thomas; Heiligenhaus, Arnd

    2015-04-01

    Abatacept (ABA), a selective T cell costimulation modulator that binds to CD80 and CD86 on antigen-presenting cells, was investigated for its antiinflammatory effect in treating severe chronic uveitis associated with juvenile idiopathic arthritis (JIA). Our retrospective study was conducted by members of the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC). Patients with JIA who are receiving ABA treatment for active uveitis were included. In all patients, uveitis had been refractory to previous topical and systemic corticosteroids, immunosuppressives, and at least 1 tumor necrosis factor-α inhibitor. A standardized protocol was used to document uveitis (MIWGUC) and arthritis. Baseline visit and visits at 3, 6, 9, and 12 months before and after ABA start were evaluated. Primary outcome measure was defined as achievement of uveitis inactivity; secondary outcome measures were tapering of corticosteroid and/or immunosuppressive treatment, and occurrence of complications. In all, 21 patients (16 female) with active uveitis (n = 21) and arthritis (n = 18) were included (mean age 11.8 ± 3.6 yrs). In 7 of 18 patients with active arthritis at baseline, inactivity was achieved following ABA treatment. Uveitis inactivity was achieved in 11 patients, but recurred later in 8 of them, and remained active in another 10 cases. Systemic corticosteroids or immunosuppression were tapered in 3 patients, but uveitis recurred in all of them during further followup. Ocular complications secondary to uveitis were present in 17 patients at baseline, while 3 patients developed new ocular complications during followup. A sustained response to ABA was uncommon in patients with severe and refractory uveitis.

  13. A case of succinic semialdehyde dehydrogenase deficiency with status epilepticus and rapid regression.

    PubMed

    Horino, Asako; Kawawaki, Hisashi; Fukuoka, Masataka; Tsuji, Hitomi; Hattori, Yuka; Inoue, Takeshi; Nukui, Megumi; Kuki, Ichiro; Okazaki, Shin; Tomiwa, Kiyotaka; Hirose, Shinichi

    2016-10-01

    Clinical phenotypic expression of SSADH deficiency is highly heterogeneous, and some infants may develop refractory secondary generalized seizures. A 9-month-old boy manifested partial seizures, developing severe status epilepticus, and conventional antiepileptic drugs were ineffective. Use of ketamine contributed to the control of status epilepticus, achieving a reduction in frequency of partial seizures, and improving EEG findings without apparent complications. Diffusion-weighted images showed hyperintensities in the bilateral basal ganglia and fornix, and multiple T2 hyperintensity lesions were detected. (123)I-iomazenil (IMZ) SPECT revealed a decrease in binding of (123)I-iomazenil predominantly in the left temporal region by the 18th day of hospitalization. However, repeated IMZ-SPECT on the 46th day of hospitalization demonstrated almost no accumulation across a broad region, sparing the left temporal region. The patient showed rapid regression, refractory myoclonus, and severe progressive brain atrophy. IMZ-SPECT findings demonstrated reduced benzodiazepine receptor binding and its dynamic changes in an SSADH-deficient patient. Considering the down regulation of the GABAA receptor, ketamine should be included in pharmacotherapeutic strategies for treatment of refractory status epilepticus in SSADH-deficient patients. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  14. 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.

  15. Can anesthetic treatment worsen outcome in status epilepticus?

    PubMed

    Sutter, Raoul; Kaplan, Peter W

    2015-08-01

    Status epilepticus refractory to first-line and second-line antiepileptic treatments challenges neurologists and intensivists as mortality increases with treatment refractoriness and seizure duration. International guidelines advocate anesthetic drugs, such as continuously administered high-dose midazolam, propofol, and barbiturates, for the induction of therapeutic coma in patients with treatment-refractory status epilepticus. The seizure-suppressing effect of anesthetic drugs is believed to be so strong that some experts recommend using them after benzodiazepines have failed. Although the rationale for the use of anesthetic drugs in patients with treatment-refractory status epilepticus seems clear, the recommendation of their use in treating status epilepticus is based on expert opinions rather than on strong evidence. Randomized trials in this context are lacking, and recent studies provide disturbing results, as the administration of anesthetics was associated with poor outcome independent of possible confounders. This calls for caution in the straightforward use of anesthetics in treating status epilepticus. However, there are still more questions than answers, and current evidence for the adverse effects of anesthetic drugs in patients with status epilepticus remains too limited to advocate a change of treatment algorithms. In this overview, the rationale and the conflicting clinical implications of anesthetic drugs in patients with treatment-refractory status epilepticus are discussed, and remaining questions are elaborated. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

  16. 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

  17. Developing the Pediatric Refractory Epilepsy Questionnaire: a pilot study.

    PubMed

    Purusothaman, Vaishnavi; Ryther, Robin C C; Bertrand, Mary; Harker, Lisa A; Jeffe, Donna B; Wallendorf, Michael; Smyth, Matthew D; Limbrick, David D

    2014-08-01

    Up to 14% of children with epilepsy continue to experience seizures despite having appropriate medical therapy and develop medically refractory epilepsy (MRE). Assessing clinical outcomes and therapeutic efficacy in children with MRE undergoing palliative epilepsy surgery has been challenging because of the lack of a quantitative instrument capable of estimating the clinical status of these patients. The ideal instrument would at once consider seizure control, neurodevelopment, caregiver burden, and quality of life. The purpose of this study was to develop and pilot the Pediatric Refractory Epilepsy Questionnaire (PREQ), a quantitative instrument to assess the severity and individual burden of epilepsy in children with MRE undergoing palliative epilepsy treatments. The caregivers of 25 patients with MRE completed the PREQ and the Quality of Life in Childhood Epilepsy (QOLCE) measure and participated in a semistructured interview. Medical records of the patients were reviewed, an Early Childhood Epilepsy Severity Scale (E-CHESS) score was calculated, and a Global Assessment of Severity of Epilepsy (GASE) score was obtained for each patient. The initial PREQ was modified based on the analysis of responses, association with previously validated scales, comments from caregivers, and expertise of the PREQ panelists. Pediatric Refractory Epilepsy Questionnaire subscale scores were calculated based on clinical paradigm and compared with independent measures of seizure severity and quality of life. Significant correlations were observed between the seizure severity subscale and the GASE score (r=0.55) and between the mood subscale and the well-being score (r=0.61) on the QOLCE. Significant correlations were also observed between the caregiver rating of seizure severity and the GASE score (r=0.53), the social activity score (r=0.57), and the behavior score (r=0.43) on the QOLCE. Correlations between the caregiver rating of quality of life and the quality of life score (r=0

  18. Assessment and Management of Treatment-Refractory Obsessive-Compulsive Disorder in Children

    PubMed Central

    Bloch, Michael H.; Storch, Eric A.

    2015-01-01

    OBJECTIVE To review the assessment and treatment of treatment-refractory pediatric obsessive-compulsive disorder (OCD). METHOD A PubMed search was conducted to identify controlled trials in pediatric OCD. Additionally, practice guidelines for the treatment of adults and children were further reviewed for references in treatment-refractory OCD across the lifespan. RESULTS Pharmacotherapy with selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy are effective treatments for pediatric OCD. Evidence suggests that CBT is additionally effective even in pediatric patients with refractory OCD symptoms. Antipsychotic augmentation, raising SSRI dosage, and several glutamate-modulating agents have some evidence of efficacy in adults with treatment-refractory OCD but have not been studied in pediatric populations. CONCLUSION Several pharmacological treatment options exist for children with refractory OCD symptoms. However, little evidence-based data exist to guide treatment for our most challenging pediatric OCD patients. Further research is needed to evaluate the efficacy/side-effect profile of commonly used interventions in treatment-refractory pediatric OCD. PMID:25791142

  19. Predictors of Outcome of Convulsive Status Epilepticus Among an Egyptian Pediatric Tertiary Hospital.

    PubMed

    Halawa, Eman F; Draz, Iman; Ahmed, Dalia; Shaheen, Hala A

    2015-11-01

    Convulsive status epilepticus is a common neurologic emergency in pediatrics. We aimed to study the etiology, clinical features, and prognostic factors among pediatric patients with convulsive status epilepticus. Seventy patients were included in this cohort study from pediatric emergency department of the specialized Children Hospital of Cairo University. The outcome was evaluated using the Glasgow Outcome Score. Acute symptomatic etiology was the most common cause of convulsive status epilepticus. Refractory convulsive status epilepticus was observed more significantly in cases caused by acute symptomatic etiologies. The outcome was mortality in 26 (37.1%) patients, severe disability in 15 (21.4%), moderate disability in 17 (24.3%), and good recovery in 12 (17.1%) patients. The significant predictor of mortality was lower modified Glasgow Coma Scale score on admission, whereas lower modified Glasgow Coma Scale score on admission and refractory convulsive status epilepticus were the significant predictors for disability and mortality. © The Author(s) 2015.

  20. Determinants and predictors of outcome in super refractory status epilepticus--a developing country perspective.

    PubMed

    Jayalakshmi, Sita; Ruikar, Devashish; Vooturi, Sudhindra; Alladi, Suvarna; Sahu, Sambit; Kaul, Subhash; Mohandas, Surath

    2014-11-01

    Super refractory status epilepticus (SRSE) is a recent entity. There is limited information about the etiology and outcome of SRSE from developing countries. We evaluated determinants and predictors of outcome in patients with convulsive SRSE in Indian population. In this open cohort study, data of patients with convulsive SE admitted in neurointensive care unit (NICU) from 2005 to 2013 was retrospectively analyzed. Regression and survival analysis was done for outcome of patients divided into non refractory SE (NRSE), refractory SE (RSE), and SRSE groups. The primary outcome for analysis was in hospital mortality. Also functional outcome at 6 months was graded according to the Glasgow outcome scale (GOS), and classified as good (GOS 4 and 5) and poor (GOS 1, 2 and 3) outcome groups. Out of 177 patients with SE, 105 (59.3%) had NRSE; 72 (40.7%) had RSE of which 30 (16.9% of 177) were sub-classified as SRSE. SRSE was frequent (39%) in children (p<0.01), elderly (21.7%; p<0.003), and in incident SE (82.1%, p=0.05). Encephalitis was the commonest etiology in RSE (30.9%, p=0.015), SRSE (66.7%, p<0.001) than NRSE (12.3%). Encephalitis (β=8.250 (1.8-37.82); p=0.007) was the determinant of the progression of SE to SRSE. Overall mortality was 19.2%, highest in SRSE (40.0%) followed by RSE (35.7%), both significantly (p<0.001) higher than NRSE (6.7%). Mortality was high in patients with encephalitis than other etiologies (39.1% vs. 12.1%; p=0.001). Acidosis predicted mortality in the entire cohort (β=7.313 (1.6-32.58); p=0.009); however none of the variables predicted mortality in SRSE patients. At 6 months follow up only 33.3% of patients with SRSE were in GOS good outcome group when compared to RSE (33.3% vs. 57.1%; p=0.055), and NRSE (33.3% vs. 79.1%; p<0.0001). SRSE is common in children, elderly, and incident SE. Encephalitis was the determinant of progression of SE to SRSE. None of the variables predicted mortality in SRSE patients. Sixty percent of patients with

  1. Illness identity in young adults with refractory epilepsy.

    PubMed

    Luyckx, Koen; Oris, Leen; Raymaekers, Koen; Rassart, Jessica; Moons, Philip; Verdyck, Ludo; Mijnster, Teus; Mark, Ruth E

    2018-03-01

    Refractory epilepsy is an intrusive condition with important implications for daily functioning in emerging and young adulthood. The present study examined the degree to which refractory epilepsy is integrated in one's identity, and examined how such a sense of illness identity was related to health-related quality of life (HRQOL). A total of 121 18- to 40-year-old patients with refractory epilepsy (56.2% women) completed self-report questionnaires assessing the four illness identity states of acceptance, enrichment, engulfment, and rejection (Illness Identity Questionnaire (IIQ)); HRQOL (Quality of Life in Epilepsy Inventory - 31); and seizure frequency and severity (Liverpool Seizure Severity Scale (LSSS)). Illness identity scores were compared with a sample of 191 patients with a nonneurological chronic disease (congenital heart disease). Hierarchical regression analyses were conducted to assess the predictive value of illness identity for HRQOL when simultaneously controlling for demographic and clinical features. Patients with refractory epilepsy scored higher on rejection and engulfment and lower on acceptance when compared with patients with congenital heart disease. Further, seizure severity and number of medication side-effects were positively related to engulfment and negatively to acceptance. Finally, when simultaneously controlling for various demographic and clinical variables, illness identity significantly predicted HRQOL (with engulfment being the strongest and most consistent predictor). The extent to which patients with refractory epilepsy succeed in integrating their illness into their identity may have important implications for HRQOL. Clinicians should be especially attentive for signs that patients feel engulfed by their epilepsy. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2018-06-15

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

  3. 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.

  4. From intravenous to enteral ketogenic diet in PICU: A potential treatment strategy for refractory status epilepticus.

    PubMed

    Chiusolo, F; Diamanti, A; Bianchi, R; Fusco, L; Elia, M; Capriati, T; Vigevano, F; Picardo, S

    2016-11-01

    Ketogenic diet (KD) has been used to treat refractory status epilepticus (RSE). KD is a high-fat, restricted-carbohydrate regimen that may be administered with different fat to protein and carbohydrate ratios (3:1 and 4:1 fat to protein and carbohydrate ratios). Other ketogenic regimens have a lower fat and higher protein and carbohydrate ratio to improve taste and thus compliance to treatment. We describe a case of RSE treated with intravenous KD in the Pediatric Intensive Care Unit (PICU). An 8-year-old boy was referred to the PICU because of continuous tonic-clonic and myoclonic generalized seizures despite several antiepileptic treatments. After admission he was intubated and treated with intravenous thiopental followed by ketamine. Seizures continued with frequent myoclonic jerks localized on the face and upper arms. EEG showed seizure activity with spikes on rhythmic continuous waves. Thus we decided to begin KD. The concomitant ileus contraindicated KD by the enteral route and we therefore began IV KD. The ketogenic regimen consisted of conventional intravenous fat emulsion, plus dextrose and amino-acid hyperalimentation in a 2:1 then 3:1 fat to protein and carbohydrate ratio. Exclusive IV ketogenic treatment, well tolerated, was maintained for 3 days; peristalsis then reappeared so KD was continued by the enteral route at 3:1 ratio. Finally, after 8 days and no seizure improvement, KD was deemed unsuccessful and was discontinued. Our experience indicates that IV KD may be considered as a temporary "bridge" towards enteral KD in patients with partial or total intestinal failure who need to start KD. It allows a prompt initiation of KD, when indicated for the treatment of severe diseases such as RSE. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  5. Pediatric intensive care treatment of uncontrolled status epilepticus.

    PubMed

    Wilkes, Ryan; Tasker, Robert C

    2013-04-01

    The critically ill mechanically ventilated child with ongoing seizures that are refractory to any treatment presents a distinct challenge in pediatric neurocritical care. The evidence base from randomized controlled trials on which anti-epileptic drug (AED) strategy should be used is inadequate. This review of refractory and super-refractory status epilepticus summarizes recent pediatric case series regarding definitions, the second-tier AED therapies once initial anticonvulsants have failed, and the experience of high-dose midazolam, barbiturate anesthesia, and volatile anesthetics for uncontrolled status epilepticus. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Heterozygous M1V variant of ELA-2 gene mutation associated with G-CSF refractory severe congenital neutropenia.

    PubMed

    Setty, Bhuvana A; Yeager, Nicholas D; Bajwa, Rajinder P

    2011-09-01

    Severe congenital neutropenia is an autosomal recessive disorder characterized by maturation arrest at the promyelocyte/myelocyte phase in the bone marrow, absolute neutrophil count <0.5 × 10(9) /L and recurrent bacterial infections. Homozygous mutations of either HAX-1 or ELA-2 have been described. We report the case of a premature male infant with congenital neutropenia, associated with multiple infections, refractory to treatment with granulocyte colony stimulating factor who subsequently underwent matched sibling donor stem-cell transplant. He was found to be heterozygous for the M1V variant of the ELA-2 gene that we postulate to be causative for his severe neutropenia Copyright © 2011 Wiley-Liss, Inc.

  7. Two Cases of Refractory Cardiogenic Shock Secondary to Bupropion Successfully Treated with Veno-Arterial Extracorporeal Membrane Oxygenation.

    PubMed

    Heise, C William; Skolnik, Aaron B; Raschke, Robert A; Owen-Reece, Huw; Graeme, Kimberlie A

    2016-09-01

    Bupropion inhibits the uptake of dopamine and norepinephrine. Clinical effects in overdose include seizure, status epilepticus, tachycardia, arrhythmias, and cardiogenic shock. We report two cases of severe bupropion toxicity resulting in refractory cardiogenic shock, cardiac arrest, and repeated seizures treated successfully. Patients with cardiovascular failure related to poisoning may particularly benefit from extracorporeal membrane oxygenation (ECMO). These are the first cases of bupropion toxicity treated with veno-arterial EMCO (VA-ECMO) in which bupropion toxicity is supported by confirmatory testing. Both cases demonstrate the effectiveness of VA-ECMO in poisoned patients with severe cardiogenic shock or cardiopulmonary failure.

  8. 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.

  9. Infraslow status epilepticus: A new form of subclinical status epilepticus recorded in a child with Sturge-Weber syndrome.

    PubMed

    Bello-Espinosa, Luis E

    2015-08-01

    Analysis of infraslow EEG activity (ISA) has shown potential in the evaluation of patients with epilepsy and in the differentiation between focal and generalized epilepsies. Infraslow EEG activity analysis may also provide insights into the pathophysiology of refractory clinical and subclinical status epilepticus. The purpose of this report is to describe a girl with Sturge-Weber syndrome (SWS) who presented with a 96-h refractory encephalopathy and nonischemic hemiparesis and who was identified to have infraslow status epilepticus (ISSE), which successfully resolved after midazolam administration. The continuous EEG recording of a 5-year-old girl with known structural epilepsy due to Sturge-Weber syndrome is presented. The patient presented to the ED with acute confusion, eye deviation, and right hemiparesis similar to two previous admissions. Despite administration of lorazepam, fosphenytoin, phenobarbital, and valproic loads, the patient showed no improvement in the clinical condition after 48 h. The continuous video-EEG monitoring (VEM) showed continuous severe diffuse nonrhythmic asymmetric slowing but no apparent ictal activity on continuous conventional EEG recording settings. As brain CT, CTA, CTV, and complete MRI scans including DWI obtained within 72 h of presentation failed to demonstrate any ischemic changes, analysis of the EEG infraslow (ISA) activity was undertaken using LFF: 0.01 Hz and HFF: of 0.1 Hz, respectively. Continuous subclinical unilateral rhythmic ictal ISA was identified. This was only evident on the left hemisphere which correlated with the structural changes due to SWS. A trial of continuous 120 to 240 μg/kg/h of IV midazolam resulted in immediate resolution of the contralateral hemiparesis and encephalopathy. Continuous prolonged rhythmic ictal infraslow activity (ISA) can cause super-refractory subclinical focal status epilepticus. This has not been previously reported, and we propose that this be called infraslow status

  10. 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.

  11. Rapid clozapine titration in treatment-refractory bipolar disorder.

    PubMed

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

    2014-09-01

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

  12. Understanding refractory failures

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

    Bases, G.J.

    2006-01-15

    Compared to most pieces of a power plant, refractory costs very little to install. Yet, if improperly manufactured, specified, stored, mixed installed, cured, or dried, refractory may cause problems that can significantly decrease a plant's operating efficiency and flexibility. Like Rodney Dangerfield, refractory design and installation deserve more respect. 4 photos.

  13. Cytomegalovirus reactivation in patients with refractory checkpoint inhibitor-induced colitis.

    PubMed

    Franklin, Cindy; Rooms, Isabelle; Fiedler, Melanie; Reis, Henning; Milsch, Laura; Herz, Saskia; Livingstone, Elisabeth; Zimmer, Lisa; Schmid, Kurt Werner; Dittmer, Ulf; Schadendorf, Dirk; Schilling, Bastian

    2017-11-01

    Immune checkpoint inhibitors can cause severe immune-related adverse events, with immune-related diarrhea and colitis (irColitis) being among the most frequent ones. While the majority of patients with irColitis respond well to corticosteroid treatment ± other immunomodulatory drugs such as infliximab, some patients do not show resolution of their symptoms. In the present study, we analysed the frequency of therapy-refractory irColitis, the underlying cause, and useful diagnostic approaches. Between 2006 and 2016, 370 patients with metastatic malignant melanoma were treated with checkpoint inhibitors at the Department of Dermatology at the University Hospital Essen. All patients were identified for whom diarrhea and/or colitis was documented in the digital patient records. Patients who did not respond to standard immunosuppressive therapy within 2 weeks were classified as refractory. Demographic and clinical data of all patients were collected. We identified 41 patients with irColitis, the majority occurring during treatment with ipilimumab. Amongst these, 5 (12.2%) were refractory to standard immunomodulatory treatment with corticosteroids and infliximab. Therapy-refractory cases tended to show more severe inflammation in colonic biopsies (p = 0.04). In all therapy-refractory cases cytomegalovirus (CMV) was detectable. CMV-DNA in colonic biopsies and in plasma was significantly more often detectable in therapy-refractory cases (in colonic biopsies p = 0.005, in plasma: p = 0.002). Presence of serum CMV IgM and positive immunohistochemical stainings of colon biopsies for CMV were also associated with refractory colitis (p=0.021; p = 0.053). This report on CMV reactivation during management of checkpoint inhibitor-induced colitis emphasises the need for repetitive diagnostic measures in treatment-refractory irColitis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Status epilepticus due to acute encephalitis: NORSE does not necessarily mean worse.

    PubMed

    Holzer, Franz Josef; Rossetti, Andrea O

    2018-06-25

    Status epilepticus (SE), refractory status epilepticus (RSE) and superrefractory status epilepticus (SRSE) are very severe medical conditions with high mortality and a potentially poor outcome in several surviving patients. Although SE, RSE and SRSE are primarily neurological affections, these patients will be admitted to an intensive care unit (ICU) for critical care, most often mechanical ventilation and general anesthesia. When a patient enters RSE or even SRSE, his/her stay in the ICU may become longer and neurologists and ICU specialists will have to agree on whether or not it is appropriate to continue critical care. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

    NASA Technical Reports Server (NTRS)

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

    2009-01-01

    Ceramics can be defmed as a material consisting of hard brittle properties produced from inorganic and nonmetallic minerals made by firing at high temperatures. These materials are compounds between metallic and nonmetallic elements and are either totally ionic, or predominately ionic but having some covalent character. This definition allows for a large range of materials, not all applicable to refractory applications. As this report is focused on potential ceramic materials for high temperature, aggressive exposure applications, the ceramics reviewed as part of this report will focus on refractory ceramics specifically designed and used for these applications. Ceramic materials consist of a wide variety of products. Callister (2000) 1 characterized ceramic materials into six classifications: glasses, clay products, refractories, cements, abrasives, and advanced ceramics. Figure 1 shows this classification system. This review will focus mainly on refractory ceramics and cements as in general, the other classifications are neither applicable nor economical for use in large structures such as the flame trench. Although much work has been done in advanced ceramics over the past decade or so, these materials are likely cost prohibitive and would have to be fabricated off-site, transported to the NASA facilities, and installed, which make these even less feasible. Although the authors reviewed the literature on advanced ceramic refractories 2 center dot 3 center dot 4 center dot 5 center dot 6 center dot 7 center dot 8 center dot 9 center dot 10 center dot 11 center dot 12 after the review it was concluded that these materials should not be ' the focus of this report. A review is in progress on materials and systems for prefabricated refractory ceramic panels, but this review is focusing more on typical refractory materials for prefabricated systems, which could make the system more economically feasible. Refractory ceramics are used for a wide variety of applications

  16. Refractory celiac disease and EATL patients show severe malnutrition and malabsorption at diagnosis.

    PubMed

    Wierdsma, Nicolette J; Nijeboer, Petula; de van der Schueren, Marian A E; Berkenpas, Marijke; van Bodegraven, Ad A; Mulder, Chris J J

    2016-06-01

    Refractory celiac disease type II (RCDII) and EATL (Enteropathy Associated T-cell Lymphoma) are (pre)malignant complications of celiac disease (CD). Data on malnutrition and intestinal absorption is lacking in these patients. Therefore, the aim of the study is to comprehensively assess nutritional status and intestinal absorption capacity of patients with RCDII and EATL, compared with data of newly diagnosed CD patients. Observational study in tertiary care setting in RCDII (n = 24, 63.8 ± 8.2 y), EATL (n = 25, 62.3 ± 5.7 y) and CD patients (n = 43, 45.6 ± 14.8 y). At diagnosis, anthropometry (BMI, unintentional weight loss, fat-free mass index (FFMI), handgrip strength (HGS), nutritional intake, fecal losses and Resting Energy Expenditure (REE)) were assessed. Low BMI (<18.5) was more often observed in RCDII patients than in CD or EATL patients (in 33%, 12% and 12%, respectively, p = 0.029). EATL patients more frequently had unintentional weight loss (>10%) than CD or RCDII patients (in 58%, 19% and 39% of patients, respectively; p = 0.005/0.082). Energy malabsorption (<85%) was detected in 44% and 33% of RCDII and EATL patients, vs 21.6% in CD (NS). Fecal energy losses were higher in RCDII than in CD patients (589 ± 451 vs 277 ± 137 kcal/d, p = 0.017). REE was underestimated by predicted-REE with>10% in 60% of RCDII, 89% of EATL, and 38% of CD patients (p = 0.006). Low FFMI and HGS were detected in one third and two thirds of all patients, respectively. The nutritional status of patients with RCDII and EATL is inferior compared with untreated naïve CD patients at presentation. Both malabsorption as well as hypermetabolism contribute to malnutrition. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. 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.

  18. Diagnostic yield of capsule endoscopy in refractory celiac disease.

    PubMed

    Barret, Maximilien; Malamut, Georgia; Rahmi, Gabriel; Samaha, Elia; Edery, Joël; Verkarre, Virginie; Macintyre, Elizabeth; Lenain, Emilie; Chatellier, Gilles; Cerf-Bensussan, Nadine; Cellier, Christophe

    2012-10-01

    Capsule endoscopy (CE) allows for the assessment of the small bowel in numerous intestinal diseases, including celiac disease (CD). The main advantage of CE is the complete visualization of the intestinal mucosal surface. The objective of this study was to investigate whether CE can predict the severity of CD and detect complications. We retrospectively studied the medical files of 9 patients with symptomatic CD, 11 patients with refractory celiac disease type I (RCDI) and 18 patients with refractory celiac disease type II (RCDII), and 45 patients without CD who were investigated both CE and upper endoscopy or enteroscopy. The type of CD was diagnosed on the basis of a centralized histological review, flow cytometry analysis of intraepithelial lymphocytes, and the analysis of T-cell receptor rearrangement by multiplex polymerase chain reaction. A total of 47 CEs (10, 11, and 26 CEs in the symptomatic CD, RCDI, and RCDII groups, respectively) from the 38 celiac patients and 47 CEs from the 45 nonceliac patients were retrospectively reviewed. Villous atrophy, numerous, or distally located ulcers were more frequent in celiac patients than in controls. Among celiac patients, CE was of acceptable quality in 96% of cases and was complete in 62% of cases. The concordance of CE with histology for villous atrophy was better than that of optic endoscopy (κ coefficient =0.45 vs. 0.24, P<0.001). Extensive mucosal damage on CE was associated with low serum albumin (P=0.003) and the RCDII form (P=0.02). Three cases of overt lymphoma were detected by CE during the follow-up. CE findings have a satisfactory concordance with histology and nutritional status in patients with symptomatic or refractory CD. Moreover, CE may predict the type of RCD and allows for the early detection of overt lymphoma.

  19. 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.

  20. Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies.

    PubMed

    Petit-Pedrol, Mar; Armangue, Thaís; Peng, Xiaoyu; Bataller, Luis; Cellucci, Tania; Davis, Rebecca; McCracken, Lindsey; Martinez-Hernandez, Eugenia; Mason, Warren P; Kruer, Michael C; Ritacco, David G; Grisold, Wolfgang; Meaney, Brandon F; Alcalá, Carmen; Sillevis-Smitt, Peter; Titulaer, Maarten J; Balice-Gordon, Rita; Graus, Francesc; Dalmau, Josep

    2014-03-01

    and limbic involvement), and two had opsoclonus-myoclonus. Overall, 12 of 15 patients for whom treatment and outcome were assessable had full (three patients) or partial (nine patients) response to immunotherapy or symptomatic treatment, and three died. Patients' antibodies caused a selective reduction of GABAA receptor clusters at synapses, but not along dendrites, without altering NMDA receptors and gephyrin (a protein that anchors the GABAA receptor). High titres of serum and CSF GABAA receptor antibodies are associated with a severe form of encephalitis with seizures, refractory status epilepticus, or both. The antibodies cause a selective reduction of synaptic GABAA receptors. The disorder often occurs with GABAergic and other coexisting autoimmune disorders and is potentially treatable. The National Institutes of Health, the McKnight Neuroscience of Brain Disorders, the Fondo de Investigaciones Sanitarias, Fundació la Marató de TV3, the Netherlands Organisation for Scientific Research (Veni-incentive), the Dutch Epilepsy Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Identification of platelet refractoriness in oncohematologic patients

    PubMed Central

    Ferreira, Aline Aparecida; Zulli, Roberto; Soares, Sheila; de Castro, Vagner; Moraes-Souza, Helio

    2011-01-01

    OBJECTIVES: To identify the occurrence and the causes of platelet refractoriness in oncohematologic patients. INTRODUCTION: Platelet refractoriness (unsatisfactory post-transfusion platelet increment) is a severe problem that impairs the treatment of oncohematologic patients and is not routinely investigated in most Brazilian services. METHODS: Forty-four episodes of platelet concentrate transfusion were evaluated in 16 patients according to the following parameters: corrected count increment, clinical conditions and detection of anti-platelet antibodies by the platelet immunofluorescence test (PIFT) and panel reactive antibodies against human leukocyte antigen class I (PRA-HLA). RESULTS: Of the 16 patients evaluated (median age: 53 years), nine (56%) were women, seven of them with a history of pregnancy. An unsatisfactory increment was observed in 43% of the transfusion events, being more frequent in transfusions of random platelet concentrates (54%). Platelet refractoriness was confirmed in three patients (19%), who presented immunologic and non-immunologic causes. Alloantibodies were identified in eight patients (50%) by the PIFT and in three (19%) by the PRA-HLA. Among alloimmunized patients, nine (64%) had a history of transfusion, and three as a result of pregnancy (43%). Of the former, two were refractory (29%). No significant differences were observed, probably as a result of the small sample size. CONCLUSION: The high rate of unsatisfactory platelet increment, refractoriness and alloimmunization observed support the need to set up protocols for the investigation of this complication in all chronically transfused patients, a fundamental requirement for the guarantee of adequate management. PMID:21437433

  2. Improved refractory performance through partnership

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

    Linck, F.E.; Peters, D.

    1995-12-31

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

  3. Review and update of the Hong Kong Epilepsy Guideline on status epilepticus.

    PubMed

    Fung, E Lw; Fung, B Bh

    2017-02-01

    Convulsive status epilepticus is the most extreme form of seizure. It is a medical and neurological emergency that requires prompt and appropriate treatment. Treatment of convulsive status epilepticus is usually divided into stages/steps. The International League Against Epilepsy has released a new definition of status epilepticus that may help to unify the definition in future studies. Over the last few years new information has become available regarding its management. The Rapid Anticonvulsant Medication Prior to Arrival Trial demonstrated non-inferiority of intramuscular midazolam in early status epilepticus compared with intravenous lorazepam. Valproate and levetiracetam have also emerged as possible alternatives to phenytoin in established status epilepticus. The potential role of lacosamide in this stage of status epilepticus remains to be defined. The ongoing Established Status Epilepticus Treatment Trial may help to determine the most effective treatment for benzodiazepine-resistant status epilepticus. Management of refractory status epilepticus and super-refractory status epilepticus remains mostly non-evidence-based. Increasing recognition of a possible autoimmune aetiology has led to the use of immune-modulation in super-refractory status epilepticus. Ketamine is also increasingly used in this challenging condition. There are also reports of potential use of a ketogenic diet and magnesium.

  4. [Severe pulmonary embolism revealed by status epilepticus].

    PubMed

    Allou, N; Coolen-Allou, N; Delmas, B; Cordier, C; Allyn, J

    2016-12-01

    High-risk pulmonary embolism (PE) is associated with high mortality rate (>50%). In some cases, diagnosis of PE remains a challenge with atypical presentations like in this case report with a PE revealed by status epilepticus. We report the case of a 40-year-old man without prior disease, hospitalized in ICU for status epilepticus. All paraclinical examinations at admission did not show any significant abnormalities (laboratory tests, cardiologic and neurological investigations). On day 1, he presented a sudden circulatory collapse and echocardiography showed right intra-auricular thrombus. He was treated by thrombolysis and arteriovenous extracorporeal membrane oxygenation. After stabilization, computed tomography showed severe bilateral PE. He developed multi-organ failure and died 4days after admission. Pulmonary embolism revealed by status epilepticus has rarely been reported and is associated with poor prognosis. Physicians should be aware and think of the possibility of PE in patients with status epilepticus without any history or risk factors of seizure and normal neurological investigations. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Role of levetiracetam in refractory seizures due to a rare progressive myoclonic epilepsy: Lafora body disease

    PubMed Central

    Hashmi, Mubashira; Saleem, Feroza; Mustafa, Muhammad Shahid; Sheerani, Mughis; Ehtesham, Zeeshan; Siddiqui, Khurram

    2010-01-01

    Lafora disease is one of the rare, most fatal progressive myoclonic epilepsies reported. We present a case of a teenager with intractable seizures and progressive mental decline, diagnosed as Lafora body disease on axillary skin biopsy. He was admitted with status epilepticus with refractory myoclonic and generalised tonic clonic seizures. Despite on maximum doses of multiple antiepileptic drugs and infusions of propofol and midazolam, his seizures were refractory to all forms of medical therapy tried. Levetiracetam (LEV), a pyrrolidine derivative, was introduced; he showed a prompt response and was weaned off successfully from infusions of anticonvulsants and mechanical ventilation within 48 h of introduction of LEV, followed by an almost seizure-free status. PMID:22791845

  6. Refractory Wear Mechanisms in the Nonferrous Metal Industry: Testing and Modeling Results

    NASA Astrophysics Data System (ADS)

    Gregurek, D.; Ressler, A.; Reiter, V.; Franzkowiak, A.; Spanring, A.; Prietl, T.

    2013-11-01

    Nonferrous pyrometallurgical processes today operate at a high intensity requiring the best standards for the furnace refractory systems. From one plant to another, there is a range of process conditions such as temperature, slag chemistry, and feed types, and each of these parameters can influence refractory life. It is generally understood that process changes at plants can impact refractory life. The ability to test and understand refractory responses to a wide range of furnace operating conditions is therefore important. The RHI Technology Centre in Leoben, Austria is well equipped with laboratory and pilot plant facilities to evaluate refractory suitability over the range of conditions encountered in modern nonferrous pyrometallurgical systems. This article describes refractory testing at the RHI Technology Centre of the impact of two metallurgical slags on a number of different RHI test bricks. The slags were a fayalite slag and a calcium ferrite slag supplied by two smelter plants. High-temperature corrosion tests were carried out in a 250-mm-diameter induction furnace and a 165-mm-diameter short rotary kiln; each unit was lined with a number of refractory bricks and tested against attack by the particular slag. After testing, the refractory bricks were subjected to several laboratory tests to determine the extent of corrosion. Optimal refractory choices for the customers' plants were developed based on the test results.

  7. A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study.

    PubMed

    Chevallier, P; Labopin, M; Turlure, P; Prebet, T; Pigneux, A; Hunault, M; Filanovsky, K; Cornillet-Lefebvre, P; Luquet, I; Lode, L; Richebourg, S; Blanchet, O; Gachard, N; Vey, N; Ifrah, N; Milpied, N; Harousseau, J-L; Bene, M-C; Mohty, M; Delaunay, J

    2011-06-01

    A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy+Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36±4%, respectively. Disease status (relapse <12 months, including refractory patients), FLT3-ITD-positive status and high-risk cytogenetics were the three strongest independent adverse prognostic factors for OS and EFS in this series. We then defined three subgroups with striking different outcomes at 2 years: no adverse factor (favourable, N=36): OS 58%, EFS 45%; one adverse factor (intermediate, N=54): OS 37%, EFS 31%; two or three adverse factors (poor, N=43): OS 12%, EFS 12% (P<10(-4), P=0.001). This new simplified Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.

  8. Factors associated with treatment delays in pediatric refractory convulsive status epilepticus.

    PubMed

    Sánchez Fernández, I; Gaínza-Lein, M; Abend, N S; Anderson, A E; Arya, R; Brenton, J N; Carpenter, J L; Chapman, K E; Clark, J; Gaillard, W D; Glauser, T A; Goldstein, J L; Goodkin, H P; Helseth, A R; Jackson, M C; Kapur, K; Lai, Y-C; McDonough, T L; Mikati, M A; Nayak, A; Peariso, K; Riviello, J J; Tasker, R C; Tchapyjnikov, D; Topjian, A A; Wainwright, M S; Wilfong, A; Williams, K; Loddenkemper, T

    2018-05-08

    To identify factors associated with treatment delays in pediatric patients with convulsive refractory status epilepticus (rSE). This prospective, observational study was performed from June 2011 to March 2017 on pediatric patients (1 month to 21 years of age) with rSE. We evaluated potential factors associated with increased treatment delays in a Cox proportional hazards model. We studied 219 patients (53% males) with a median (25th-75th percentiles [p 25 -p 75 ]) age of 3.9 (1.2-9.5) years in whom rSE started out of hospital (141 [64.4%]) or in hospital (78 [35.6%]). The median (p 25 -p 75 ) time from seizure onset to treatment was 16 (5-45) minutes to first benzodiazepine (BZD), 63 (33-146) minutes to first non-BZD antiepileptic drug (AED), and 170 (107-539) minutes to first continuous infusion. Factors associated with more delays to administration of the first BZD were intermittent rSE (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.14-2.09; p = 0.0467) and out-of-hospital rSE onset (HR 1.5, 95% CI 1.11-2.04; p = 0.0467). Factors associated with more delays to administration of the first non-BZD AED were intermittent rSE (HR 1.78, 95% CI 1.32-2.4; p = 0.001) and out-of-hospital rSE onset (HR 2.25, 95% CI 1.67-3.02; p < 0.0001). None of the studied factors were associated with a delayed administration of continuous infusion. Intermittent rSE and out-of-hospital rSE onset are independently associated with longer delays to administration of the first BZD and the first non-BZD AED in pediatric rSE. These factors identify potential targets for intervention to reduce time to treatment. © 2018 American Academy of Neurology.

  9. Management of Status Epilepticus in Children

    PubMed Central

    Smith, Douglas M.; McGinnis, Emily L.; Walleigh, Diana J.; Abend, Nicholas S.

    2016-01-01

    Status epilepticus is a common pediatric neurological emergency. Management includes prompt administration of appropriately selected anti-seizure medications, identification and treatment of seizure precipitant(s), as well as identification and management of associated systemic complications. This review discusses the definitions, classification, epidemiology and management of status epilepticus and refractory status epilepticus in children. PMID:27089373

  10. Clinical features and course of refractory anemia with ring sideroblasts associated with marked thrombocytosis

    PubMed Central

    Broseus, Julien; Florensa, Lourdes; Zipperer, Esther; Schnittger, Susanne; Malcovati, Luca; Richebourg, Steven; Lippert, Eric; Cermak, Jaroslav; Evans, Jyoti; Mounier, Morgane; Raya, José Maria; Bailly, François; Gattermann, Norbert; Haferlach, Torsten; Garand, Richard; Allou, Kaoutar; Besses, Carlos; Germing, Ulrich; Haferlach, Claudia; Travaglino, Erica; Luno, Elisa; Pinan, Maria Angeles; Arenillas, Leonor; Rozman, Maria; Perez Sirvent, Maria Luz; Favre, Bernardine; Guy, Julien; Alonso, Esther; Ahwij, Nuhri; Jerez, Andrés; Hermouet, Sylvie; Maynadié, Marc; Cazzola, Mario; Girodon, François

    2012-01-01

    Background Refractory anemia with ring sideroblasts associated with marked thrombocytosis was proposed as a provisional entity in the 2001 World Health Organization classification of myeloid neoplasms and also in the 2008 version, but its existence as a single entity is contested. We wish to define the clinical features of this rare myelodysplastic/myeloproliferative neoplasm and to compare its clinical outcome with that of refractory anemia with ring sideroblasts and essential thrombocythemia. Design and Methods We conducted a collaborative retrospective study across Europe. Our database included 200 patients diagnosed with refractory anemia with ring sideroblasts and marked thrombocytosis. For each of these patients, each patient diagnosed with refractory anemia with ring sideroblasts was matched for age and sex. At the same time, a cohort of 454 patients with essential thrombocythemia was used to compare outcomes of the two diseases. Results In patients with refractory anemia with ring sideroblasts and marked thrombocytosis, depending on the Janus Kinase 2 V617F mutational status (positive or negative) or platelet threshold (over or below 600×109/L), no difference in survival was noted. However, these patients had shorter overall survival and leukemia-free survival with a lower risk of thrombotic complications than did patients with essential thrombocythemia (P<0.001) but better survival (P<0.001) and a higher risk of thrombosis (P=0.039) than patients with refractory anemia with ring sideroblasts. Conclusions The clinical course of refractory anemia with ring sideroblasts and marked thrombocytosis is better than that of refractory anemia with ring sideroblasts and worse than that of essential thrombocythemia. The higher risk of thrombotic events in this disorder suggests that anti-platelet therapy might be considered in this subset of patients. From a clinical point of view, it appears to be important to consider refractory anemia with ring sideroblasts and

  11. Levofloxacin for the treatment of severe refractory BK virus-associated hemorrhagic cystitis in hematopoietic stem cell transplantation recipients: A report of three cases.

    PubMed

    Toptas, Tayfur; Kaygusuz-Atagunduz, Isik; Kani, Haluk Tarik; Adiguzel, Cafer; Firatli-Tuglular, Tulin

    2014-10-01

    BK-virus (BKV) is an important etiological agent for late-onset hemorrhagic cystitis (HC) in patients undergoing hematopoietic stem cell transplantation. Late-onset HC causes significant morbidity among these patients. Therapeutic approaches remain predominantly symptomatic. Several treatment options have been used with variable success rates. Cidofovir has the highest specificity against BKV; however, its lack of availability in the majority of countries, high costs and potential nephrotoxic effects limit its use. The present study reports three cases of severe and prolonged BKV-associated HC (BKHC). HC was resolved in all three of the patients using oral levofloxacin. Thus, levofloxacin may be an effective treatment modality for achieving complete clinical and molecular response in patients with refractory, severe BKHC.

  12. Immunomodulatory therapy in refractory/recurrent ovarian cancer.

    PubMed

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

    2015-04-01

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

  13. 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

  14. Refractory Cardiogenic Shock During Tramadol Poisoning: A Case Report.

    PubMed

    Belin, Nicolas; Clairet, Anne-Laure; Chocron, Sidney; Capellier, Gilles; Piton, Gaël

    2017-04-01

    Tramadol is a weak opioid analgesic indicated for the treatment of moderate to severe pain. Tramadol intoxication can be lethal, and this drug is frequently involved in voluntary overdose. Classically, tramadol intoxication is associated with neurological and respiratory side effects. In contrast, cardiac effects are poorly documented in the literature. We report a case of severe tramadol intoxication, with plasma concentration 20 times the toxic threshold, complicated by refractory cardiogenic shock, successfully treated by extra corporeal life support (ECLS) with a favorable cardiac outcome and ECLS weaning at day 10. Seizure, clonus, and nonreactive mydriasis were present during 4 days, and complete awakening was delayed to day 15. Poisoning caused by high doses of tramadol can lead to refractory cardiogenic shock, and ECLS can be considered as effective rescue therapy in this context.

  15. Levofloxacin for the treatment of severe refractory BK virus-associated hemorrhagic cystitis in hematopoietic stem cell transplantation recipients: A report of three cases

    PubMed Central

    TOPTAS, TAYFUR; KAYGUSUZ-ATAGUNDUZ, ISIK; KANI, HALUK TARIK; ADIGUZEL, CAFER; FIRATLI-TUGLULAR, TULIN

    2014-01-01

    BK-virus (BKV) is an important etiological agent for late-onset hemorrhagic cystitis (HC) in patients undergoing hematopoietic stem cell transplantation. Late-onset HC causes significant morbidity among these patients. Therapeutic approaches remain predominantly symptomatic. Several treatment options have been used with variable success rates. Cidofovir has the highest specificity against BKV; however, its lack of availability in the majority of countries, high costs and potential nephrotoxic effects limit its use. The present study reports three cases of severe and prolonged BKV-associated HC (BKHC). HC was resolved in all three of the patients using oral levofloxacin. Thus, levofloxacin may be an effective treatment modality for achieving complete clinical and molecular response in patients with refractory, severe BKHC. PMID:25202408

  16. 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.

  17. [Surgical management of refractory dysphagia and aspiration].

    PubMed

    Wang, Jian; Li, Wuyi; Liu, Jianhan; Xu, Chunxiao; Yang, Dahai; Huo, Hong; Tian, Xu; Zhang, Zhuhua; Chen, Yu

    2015-02-01

    To explore the methods and results of surgical management for refractory dysphagia and aspiration. The clinical data of 24 refractory dysphagia and aspiration patients who accepted surgical management were retrospectively analysed. Twenty-four refractory dysphagia and aspiration patients accepted 26 operations between 2001 and 2014. Of the 26 operations, 17 were cricopharyngeal myectomy (CPM), 6 were scarectomy, 3 were laryngeal-tracheal separation. No severe complications occurred. Assessments of dysphagia were completed in 18 operations before and after operation. Aspiration scores of videofluoroscopic swallowing study (VFSS) were 4.50 [4.00;7.00] vs 2.00 [1.00; 3.25], P = 0.000; swallow dysfunction scroes of VFSS were 5.00 [4.00; 12.00] vs 1.00 [1.50; 10.00], P = 0.001; aspiration scores of fibroptic endoscopic evaluation of swallowing (FEES) were 4.00 [5.00; 7.00] vs 2.00 [1.75; 3.00], P = 0.000. But the surgical results for post radiotherapy dysphagia were not successful (n = 5): aspiration scores of VFSS were 7.00 [6.50; 8.00] vs 6.00 [2.00; 7.50], P = 0.109;swallow dysfunction scroes of VFSS were 12.00 [10.50; 12.00] vs 12.00 [7.50; 12.00], P = 0.180;aspiration scores of FEES were 7.00 [6.50; 8.00] vs 6.00 [2.00; 7.50], P = 0.109. Surgical management was effective for refractory dysphagia and aspiration, but the surgical indication selection should be strict.

  18. Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus.

    PubMed

    Arya, Ravindra; Peariso, Katrina; Gaínza-Lein, Marina; Harvey, Jessica; Bergin, Ann; Brenton, J Nicholas; Burrows, Brian T; Glauser, Tracy; Goodkin, Howard P; Lai, Yi-Chen; Mikati, Mohamad A; Fernández, Iván Sánchez; Tchapyjnikov, Dmitry; Wilfong, Angus A; Williams, Korwyn; Loddenkemper, Tobias

    2018-04-27

    To describe the efficacy and safety of ketogenic diet (KD) for convulsive refractory status epilepticus (RSE). RSE patients treated with KD at the 6/11 participating institutions of the pediatric Status Epilepticus Research Group from January-2011 to December-2016 were included. Patients receiving KD prior to the index RSE episode were excluded. RSE was defined as failure of ≥2 anti-seizure medications, including at least one non-benzodiazepine drug. Ketosis was defined as serum beta-hydroxybutyrate levels >20 mg/dl (1.9 mmol/l). Outcomes included proportion of patients with electrographic (EEG) seizure resolution within 7 days of starting KD, defined as absence of seizures and ≥50% suppression below 10 μV on longitudinal bipolar montage (suppression-burst ratio ≥50%); time to start KD after onset of RSE; time to achieve ketosis after starting KD; and the proportion of patients weaned off continuous infusions 2 weeks after KD initiation. Treatment-emergent adverse effects (TEAEs) were also recorded. Fourteen patients received KD for treatment of RSE (median age 4.7 years, interquartile range [IQR] 5.6). KD was started via enteral route in 11/14 (78.6%) patients. KD was initiated a median of 13 days (IQR 12.5) after the onset of RSE, at 4:1 ratio in 8/14 (57.1%) patients. Ketosis was achieved within a median of 2 days (IQR 2.0) after starting KD. EEG seizure resolution was achieved within 7 days of starting KD in 10/14 (71.4%) patients. Also, 11/14 (78.6%) patients were weaned off their continuous infusions within 2 weeks of starting KD. TEAEs, potentially attributable to KD, occurred in 3/14 (21.4%) patients, including gastro-intestinal paresis and hypertriglyceridemia. Three month outcomes were available for 12/14 (85.7%) patients, with 4 patients being seizure-free, and 3 others with decreased seizure frequency compared to pre-RSE baseline. This series suggests efficacy and safety of KD for treatment of pediatric RSE. Copyright © 2018

  19. Use of Recombinant Factor VIIa in a Pediatric Patient With Initial Presentation of Refractory Acute Immune Thrombocytopenic Purpura and Severe Bleeding

    PubMed Central

    Gurion, Reut; Siu, Anita; Weiss, Aaron R.; Masterson, Margaret

    2012-01-01

    Severe bleeding in acute immune thrombocytopenic purpura (ITP) is rare but can cause significant complications to the patient. Here we report the case of a pediatric patient with acute ITP and hematuria refractory to anti-D immune globulin, high dose intravenous immunoglobulin G, and high dose steroids. Her hematuria was successfully treated with recombinant factor VIIa (rFVIIa). While further investigation on the use of rFVIIa in ITP is warranted, this case report contributes to the pediatric literature for its use during the course of an initial presentation of ITP with hemorrhagic complications. PMID:23258971

  20. Engineering Antimicrobials that are Refractory to Resistance Development.

    USDA-ARS?s Scientific Manuscript database

    Multi-drug resistant pathogens are a serious problem in modern health care and there is a need for novel antimicrobials that are refractory to resistance development. Several US government agencies (FDA, CDC and NIH) recommend avoiding the use of broad range antimicrobials, a practice that is known...

  1. Electromyographic indices, orofacial myofunctional status and temporomandibular disorders severity: A correlation study.

    PubMed

    De Felício, Cláudia Maria; Ferreira, Cláudia Lúcia Pimenta; Medeiros, Ana Paula Magalhães; Rodrigues Da Silva, Marco Antonio M; Tartaglia, Gianluca M; Sforza, Chiarella

    2012-04-01

    This study examined whether there is an association between surface electromyography (EMG) of masticatory muscles, orofacial myofunction status and temporomandibular disorder (TMD) severity scores. Forty-two women with TMD (mean 30 years, SD 8) and 18 healthy women (mean 26 years, SD 6) were examined. According to the Research Diagnostic Criteria for TMD (RDC/TMD), all patients had myogenous disorders plus disk displacements with reduction. Surface EMG of masseter and temporal muscles was performed during maximum teeth clenching either on cotton rolls or in intercuspal position. Standardized EMG indices were obtained. Validated protocols were used to determine the perception severity of TMD and to assess orofacial myofunctional status. TMD patients showed more asymmetry between right and left muscle pairs, and more unbalanced contractile activities of contralateral masseter and temporal muscles (p<0.05, t-test), worse orofacial myofunction status and higher TMD severity scores (p<0.05, Mann-Whitney test) than healthy subjects. Spearman coefficient revealed significant correlations between EMG indices, orofacial myofunctional status and TMD severity (p<0.05). In conclusion, these methods will provide useful information for TMD diagnosis and future therapeutic planning. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Refractory metals for ARPS AMTEC cells

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

    Svedberg, R.C.; Sievers, R.C.

    1998-07-01

    Alkali Metal Thermal-to-Electric Converter (AMTEC) cells for the Advanced Radioisotope Power Systems (ARPS) program are being developed with refractory metals and alloys as the basic structural materials. AMTEC cell efficiency increases with cell operating temperature. For space applications, long term reliability and high efficiency are essential and refractory metals were selected because of their high temperature strength, low vapor pressure, and compatibility with sodium. However, refractory metals are sensitive to oxygen, nitrogen and hydrogen contamination and refractory metal cells cannot be processed in air. Because of this sensitivity, new manufacturing and processing techniques are being developed. In addition to structuralmore » elements, development of other refractory metal components for the AMTEC cells, such as the artery and evaporator wicks, pinchoff tubes and feedthroughs are required. Changes in cell fabrication techniques and processing procedures being implemented to manufacture refractory metal cells are discussed.« less

  3. Propofol versus thiopental sodium for the treatment of refractory status epilepticus.

    PubMed

    Prabhakar, Hemanshu; Bindra, Ashish; Singh, Gyaninder Pal; Kalaivani, Mani

    2012-08-15

    Failure to respond to antiepileptic drugs in uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome. To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (10 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library 2012), and MEDLINE (1946 to May week 1, 2012). We also searched (10 May 2012) ClinicalTrials.gov, The South Asian Database of Controlled Clinical Trials, and IndMED (a bibliographic database of Indian Medical Journals). All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol. Two review authors screened the search results and reviewed abstracts of relevant and eligible trials before retrieving the full text publications. One study was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE and receiving either propofol or thiopental sodium for the control of seizure activity (Rossetti 2011). This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. There was no evidence of a difference between the drugs with respect to the outcome measures such as control of seizure activity and functional outcome at three months. There is lack of robust and randomised controlled evidence that can clarify the efficacy of propofol and thiopental sodium over each other in the treatment of RSE

  4. 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

  5. A new appraisal of iodine refractory thyroid cancer.

    PubMed

    Vaisman, Fernanda; Carvalho, Denise P; Vaisman, Mario

    2015-12-01

    Thyroid cancer incidence is increasing all over the world - mostly due to an increase in the detection of small tumors that were previously undetected. A small percentage of these tumors lose the ability to uptake and/or to respond to radioiodine (RAI) therapy, especially in metastatic patients. There are several new therapeutic options that have emerged in the last 5 years to treat RAI refractory thyroid cancer patients, however, it is very important to properly identify RAI refractory patients and to clarify those appropriate for these treatments. In this review, we discuss the RAI refractory definitions and the criteria that have been suggested based on RAI uptake in the post therapy scan, as well as the response after RAI therapy and the possible molecular mechanisms involved in this process. We offer a review of the therapeutic options available at the moment and the therapeutic considerations based on a patient's individualized personal characteristics, primary tumor histology, tumor burden and location and velocity of lesion growth. © 2015 Society for Endocrinology.

  6. Efficacy and tolerability of levetiracetam for pediatric refractory epilepsy.

    PubMed

    Muramatsu, Kazuhiro; Sawaura, Noriko; Ogata, Tomomi; Makioka, Nishiki; Tomita, Keiko; Motojima, Toshino; Ida, Kuniko; Hazama, Kyoko; Arakawa, Hirokazu

    2017-03-01

    Levetiracetam has a high tolerability and is effective against various seizure types and epilepsy syndromes. However, no study has specifically evaluated the efficacy of levetiracetam in children with refractory epilepsy based on magnetic resonance imaging (MRI) findings and the presence of intellectual disability (ID). We retrospectively evaluated levetiracetam efficacy and safety in 49 pediatric patients who met the following inclusion criteria: (1) diagnosis of refractory epilepsy with first-line antiepileptic (AED) treatment ⩾2years, (2) younger than 20years old, and (3) received oral levetiracetam treatment for ⩾6months. We assessed the relationships of these outcomes with MRI findings and ID status. Eighteen (37%) patients achieved a ⩾50% reduction in seizure frequency, and the majority (78%) had no remarkable side effects. Twenty-two (45%) patients had previously been treated with more than seven antiepileptic drugs prior to levetiracetam. Among 18 patients who achieved a ⩾50% reduction in seizure frequency, 13 and 5 had negative and positive MRI findings, and 9 and 9 had and did not have ID, respectively. Our findings suggest that even for intractable pediatric cases with symptomatic etiology (i.e., MRI lesion and ID), levetiracetam has favorable efficacy for refractory epilepsy with tolerable adverse effects. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  7. Extracorporeal membrane oxygenation for refractory septic shock in adults.

    PubMed

    Park, Taek Kyu; Yang, Jeong Hoon; Jeon, Kyeongman; Choi, Seung-Hyuk; Choi, Jin-Ho; Gwon, Hyeon-Cheol; Chung, Chi Ryang; Park, Chi Min; Cho, Yang Hyun; Sung, Kiick; Suh, Gee Young

    2015-02-01

    The role of extracorporeal membrane oxygenation (ECMO) remains controversial in adult patients with refractory septic shock. We sought to describe the clinical outcomes of adult patients supported by ECMO during septic shock refractory to conventional treatment. We analysed consecutive adult patients with refractory septic shock, assisted by an ECMO system between January 2005 and December 2013 in a single-centre registry. The primary outcome was survival to hospital discharge. A total of 32 patients (21 males) received ECMO support for refractory septic shock. Of these, 14 patients (43.8%) had undergone cardiopulmonary resuscitation (CPR) and 7 patients (21.9%) did not achieve the return of spontaneous circulation until initiation of ECMO flow. ECMO was weaned off successfully in 13 patients (40.6%) and 7 patients (21.9%) survived to hospital discharge. The survivors had lower peak lactate (4.5 vs 15.1 mmol/l, P = 0.03), lower Sepsis-related Organ Failure Assessment day 3 score (15 vs 18, P = 0.01) and higher peak troponin I (32.8 vs 3.7 ng/ml, P = 0.02) than the non-survivors. None of the patients (31.3%) in whom ECMO was initiated more than 30.5 h after onset of septic shock, survived. In multivariable-adjusted models, CPR [adjusted hazard ratio (HR), 4.61; 95% confidence interval (CI), 1.55-13.69; P = 0.006] was an independent predictor of in-hospital mortality after ECMO in patients with refractory septic shock. Higher peak troponin I > 15 ng/ml (adjusted HR, 0.34; 95% CI, 0.12-0.97; P = 0.04) was associated with a lower risk of in-hospital mortality. Survival to hospital discharge remained low in adult patients with refractory septic shock despite ECMO support. Our findings suggest that implantation of ECMO during refractory septic shock could be considered in patients with severe myocardial injury but should be avoided in patients who have received CPR. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio

  8. Synthesis of refractory materials

    DOEpatents

    Holt, Joseph B.

    1984-01-01

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

  9. Synthesis of refractory materials

    DOEpatents

    Holt, J.B.

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

  10. 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.

  11. Infection-Related Death among Persons with Refractory Juvenile Idiopathic Arthritis

    PubMed Central

    Lane, Jonathan P.; Wood, Mark; Friswell, Mark; Flood, Terence J.; Foster, Helen E.

    2016-01-01

    Severe infections are emerging as major risk factors for death among children with juvenile idiopathic arthritis (JIA). In particular, children with refractory JIA treated with long-term, multiple, and often combined immunosuppressive and antiinflammatory agents, including the new biological disease-modifying antirheumatic drugs (DMARDs), are at increased risk for severe infections and death. We investigated 4 persons with JIA who died during 1994–2013, three of overwhelming central venous catheter–related bacterial sepsis caused by coagulase-negative Staphylococus or α-hemolytic Streptococcus infection and 1 of disseminated adenovirus and Epstein-Barr virus infection). All 4 had active JIA refractory to long-term therapy with multiple and combined conventional and biological DMARDs. Two died while receiving high-dose systemic corticosteroids, methotrexate, and after recent exposure to anti–tumor necrosis factor-α biological DMARDs, and 2 during hematopoietic stem cell transplantation procedure. Reporting all cases of severe infections and especially deaths in these children is of paramount importance for accurate surveillance. PMID:27648582

  12. 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.

  13. Identifying risk factors for refractory febrile neutropenia in patients with lung cancer.

    PubMed

    Fujita, Masaki; Tokunaga, Shoji; Ikegame, Satoshi; Harada, Eiji; Matsumoto, Takemasa; Uchino, Junji; Watanabe, Kentaro; Nakanishi, Yoichi

    2012-02-01

    Information about the development of febrile neutropenia in patients with solid tumors remains insufficient. In this study, we tried to identify the risk factors for refractory febrile neutropenia in patients with lung cancer. A total of 59 neutropenic fever episodes associated with anti-tumor chemotherapy for lung cancer were retrospectively analyzed. We compared patient characteristics according to their initial response to treatment with antibiotics. For 34 of 59 (58%) episodes a response to initial antibiotics was obtained whereas 25 of 59 (42%) were refractory to treatment. Multivariate analysis demonstrated independent risk factors for refractory febrile neutropenia with lung cancer. These risk factors were the severity of febrile neutropenia (odds ratio (OR) 6.11; 95% confidence interval (CI) 1.85-20.14) and C-reactive protein more than 10 mg/dl (OR 4.39; 95% CI 1.22-15.74). These factors could predict outcome for patients with lung cancer who develop refractory febrile neutropenia.

  14. Epilepsy surgery in a liver-transplanted girl with temporal lobe epilepsy and hippocampal sclerosis following PRES with status epilepticus.

    PubMed

    Dilena, Robertino; Nebbia, Gabriella; Fiorica, Lorenzo; Farallo, Marcello; Degrassi, Irene; Gozzo, Francesca; Pelliccia, Veronica; Barbieri, Sergio; Cossu, Massimo; Tassi, Laura

    2016-07-01

    Posterior reversible encephalopathy syndrome (PRES) with status epilepticus may occur after liver transplant. This may rarely lead to refractory epilepsy and hippocampal sclerosis (HS). We report the first case of epilepsy surgery in a liver-transplanted patient with refractory temporal lobe epilepsy. A 3-year-old girl underwent liver transplant for congenital biliary atresia. Four days after transplant she manifested PRES with status epilepticus, but she recovered within a couple of weeks. At the age of 5 years she started presenting complex partial seizures, that became refractory to antiepileptic drugs (AED), worsening psychosocial performances. The pre-surgical work-up identified a left HS and temporal pole alterations. A left antero-mesial temporal lobectomy was performed, leading to epilepsy remission and allowing AED withdrawal. Drug-resistant temporal lobe epilepsy and HS may occur as sequelae of PRES with status epilepticus related to liver transplant and cyclosporine use. In this setting early epilepsy surgery may reduce the time of chronic exposure to AED and severe illness due to repeated seizures. This option might have additional advantages in the subgroup of epileptic patients with liver transplant, preserving the liver from the potential damage due to multiple AED trials and their interaction with commonly used immunosuppressant drugs. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  15. Depression but Not Symptom Severity is Associated With Work and School Absenteeism in Refractory Chronic Constipation.

    PubMed

    Staller, Kyle; Barshop, Kenneth; Kuo, Braden; Ananthakrishnan, Ashwin N

    We sought to determine the patient characteristics associated with increased absenteeism and Emergency Department (ED) utilization among patients with constipation. Chronic constipation is associated with significant direct and indirect economic costs. There has been limited study of the predictors of direct and indirect costs in a population with refractory constipation. We conducted a cross-sectional cohort study of patients with chronic constipation who presented to a tertiary care center for anorectal manometry. We used standardized instruments to assess disease severity, quality of life, somatization, and psychiatric comorbidities. We used multivariable logistic regression to determine the predictors of work and school absenteeism as well as ED visits for constipation. There were 148 consecutive patients enrolled (87% female, mean age 43) of whom 32 (21.6%) had high absenteeism and 36 (24.3%) visited the ED for constipation in the past year. Patients with high absenteeism and ED visits were more likely to be depressed (56.3% vs. 18.5%, P<0.0001 for high absenteeism; 47.2% vs. 19.6%, P<0.01 for ED visits). After multivariable adjustment and sensitivity analyses, only depression (OR, 4.41; P<0.01) was associated with increased absenteeism while there was a trend toward an association between depression and ED visits (OR, 2.57; P=0.067). Symptom severity was not associated with high absenteeism or ED utilization. Among patients with chronic constipation, depression is a stronger predictor of absenteeism than symptom severity. Depression may drive a portion of the indirect costs of chronic constipation.

  16. 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.

  17. Less Common Etiologies of Status Epilepticus

    PubMed Central

    Bleck, Thomas P

    2010-01-01

    Status epilepticus is treated as a neurologic emergency and only later are the potential etiologies assessed. While sometimes the cause for status epilepticus is apparent (e.g., antiepileptic drug withdrawal), all too often it is not identified, even after extensive diagnostic testing has been performed. With emphasis on the less-common etiologies, this review will cover various probable and known causes of status epilepticus among adults, children, and those patients with refractory epilepsy. PMID:20231917

  18. 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

  19. Classical management of refractory adult immune (idiopathic) thrombocytopenic purpura.

    PubMed

    McMillan, R

    2002-03-01

    Treatment of chronic immune (idiopathic) thrombocytopenic purpura with corticosteroids and/or splenectomy results in safe platelet counts in over 70% of patients without additional treatment. Therapy of patients who are refractory to these two treatments may be difficult. The treatment approach to refractory ITP patients, described in this report, is arbitrarily divided into four levels: levels 1 through 3 represent treatments with increasing side effects; level 4 therapy may be tried when the others have failed. Patients undergoing these treatments may require concomitant intravenous gammaglobulin, high-dose corticosteroids or platelets, to maintain the platelet count in the setting of mucosal bleeding or severe thrombocytopenia. Copyright 2002, Elsevier Science Ltd. All rights reserved.

  20. Refractoriness in Sustained Visuo-Manual Control: Is the Refractory Duration Intrinsic or Does It Depend on External System Properties?

    PubMed Central

    van de Kamp, Cornelis; Gawthrop, Peter J.; Gollee, Henrik; Loram, Ian D.

    2013-01-01

    Researchers have previously adopted the double stimulus paradigm to study refractoriness in human neuromotor control. Currently, refractoriness, such as the Psychological Refractory Period (PRP) has only been quantified in discrete movement conditions. Whether refractoriness and the associated serial ballistic hypothesis generalises to sustained control tasks has remained open for more than sixty years. Recently, a method of analysis has been presented that quantifies refractoriness in sustained control tasks and discriminates intermittent (serial ballistic) from continuous control. Following our recent demonstration that continuous control of an unstable second order system (i.e. balancing a ‘virtual’ inverted pendulum through a joystick interface) is unnecessary, we ask whether refractoriness of substantial duration (∼200 ms) is evident in sustained visual-manual control of external systems. We ask whether the refractory duration (i) is physiologically intrinsic, (ii) depends upon system properties like the order (0, 1st, and 2nd) or stability, (iii) depends upon target jump direction (reversal, same direction). Thirteen participants used discrete movements (zero order system) as well as more sustained control activity (1st and 2nd order systems) to track unpredictable step-sequence targets. Results show a substantial refractory duration that depends upon system order (250, 350 and 550 ms for 0, 1st and 2nd order respectively, n = 13, p<0.05), but not stability. In sustained control refractoriness was only found when the target reverses direction. In the presence of time varying actuators, systems and constraints, we propose that central refractoriness is an appropriate control mechanism for accommodating online optimization delays within the neural circuitry including the more variable processing times of higher order (complex) input-output relations. PMID:23300430

  1. 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.

  2. 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

  3. SINTERED REFRACTORY MASS

    DOEpatents

    Williams, A.E.

    1955-09-01

    A method is given for joining sintered masses of refractory compounds. It consists in maintaining the masses in contact with each other by application of a moderate pressure, while they are at sintering temperature. The sintered masses are subjected to am applied pressure of about 1/2 to 1 ton per square inch of the surface in contact for about 10 minutes, and the temperature employed may be fropn about 1400 deg C to 2000 deg C. Refractory oxides to which the invention may be applied are beryllia, alumina, thoria, and magnesia.

  4. New-Onset Status Epilepticus in Pediatric Patients: Causes, Characteristics, and Outcomes.

    PubMed

    Jafarpour, Saba; Hodgeman, Ryan M; De Marchi Capeletto, Carolina; de Lima, Mateus Torres Avelar; Kapur, Kush; Tasker, Robert C; Loddenkemper, Tobias

    2018-03-01

    Many pediatric patients presenting with status epilepticus have no history of seizures. We retrospectively analyzed the clinical characteristics of patients aged one month to 21 years who presented during six consecutive years with convulsive status epilepticus and without a history of seizures. New-onset refractory status epilepticus was defined as status epilepticus refractory to two lines of treatment, without an identified cause in the first 48 hours. Of 460 patients with status epilepticus, 79 (17.2%) presented with new-onset status epilepticus, including four (0.9%) with new-onset refractory status epilepticus. Of those patients, 54.4% were female, and the median age was 3.5 years (IQR: 1.08 to 6.75). The median seizure duration was 20 minutes (IQR: 10 to 40 minutes). Etiology was unknown in 36.7%, symptomatic in 30.3%, provoked in 16.5%, and provoked with an existing symptomatic etiology in 16.5%. Patients were followed for a median duration of 63 months (IQR: 21 to 97). The mortality rate was 3.8%. Of 55 patients who were developmentally normal at baseline, 29.1% had a significant cognitive impairment at the last follow-up, and 20% had academic difficulties or behavioral problems. Patients with symptomatic etiology had greater odds of having cognitive and behavioral problems compared with patients with unknown etiology (odds ratio = 3.83, P = 0.012). Patients with new-onset status epilepticus are at risk for recurrent seizures, recurrent status epilepticus, death, and subsequent cognitive-behavioral impairment. Specific monitoring and care interventions might be required in this high-risk population. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Propofol versus thiopental sodium for the treatment of refractory status epilepticus (Review).

    PubMed

    Prabhakar, Hemanshu; Bindra, Ashish; Singh, Gyaninder Pal; Kalaivani, Mani

    2013-07-01

    Failure to respond to antiepileptic drugs in uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome. To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (10 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library 2012), and MEDLINE (1946 to May week 1, 2012). We also searched (10 May 2012) ClinicalTrials.gov, The South Asian Database of Controlled Clinical Trials, and IndMED (a bibliographic database of Indian Medical Journals). All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol. Two review authors screened the search results and reviewed abstracts of relevant and eligible trials before retrieving the full text publications. One study was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE and receiving either propofol or thiopental sodium for the control of seizure activity (Rossetti 2011). This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. There was no evidence of a difference between the drugs with respect to the outcome measures such as control of seizure activity and functional outcome at three months. There is lack of robust and randomised controlled evidence that can clarify the efficacy of propofol and thiopental sodium over each other in the treatment of RSE. There

  6. Cyclosporine treatment of steroid-refractory ulcerative colitis during pregnancy.

    PubMed

    Branche, Julien; Cortot, Antoine; Bourreille, Arnaud; Coffin, Benoît; de Vos, Martine; de Saussure, Philippe; Seksik, Philippe; Marteau, Philippe; Lemann, Marc; Colombel, Jean-Frédéric

    2009-07-01

    Cyclosporine is considered a safe and effective treatment of severe steroid-refractory ulcerative colitis (UC). However, few data are available concerning its safety profile in pregnant women. We report here the experience of 5 GETAID centers. In a retrospective study data on patients with severe UC treated with cyclosporine during pregnancy were extracted from medical records of consecutive patients treated between 2001 and 2007. Eight patients (median age 30.5 years old) were identified. At the time of flare-up the median duration of pregnancy was 11.5 weeks of gestation (range 4-25). Seven patients had pancolitis. All patients had more than 3 commonly used clinical and biological severity criteria. Three patients had severe endoscopic lesions and 5 patients had not. All patients received intravenous corticosteroids for at least 7 days before introduction of cyclosporine. Two patients received azathioprine during treatment with cyclosporine. No severe infections or other complications due to treatment were observed. Treatment was effective in 7/8 patients. One patient received infliximab due to cyclosporine therapy failure with a good outcome. No colectomy was performed during pregnancy. Seven pregnancies were conducted to term, but 1 in utero death occurred due to maternal absence of S-protein. Two newborns were premature, including 1 case of hypotrophy. No malformations were observed. In our experience, treatment with cyclosporine for steroid-refractory UC during pregnancy can be considered safe and effective.

  7. Refractory Gastrointestinal Bleeding: Role of Angiographic Intervention

    PubMed Central

    2013-01-01

    Although endoscopic hemostasis remains initial treatment modality for nonvariceal gastrointestinal (GI) bleeding, severe bleeding despite endoscopic management occurs in 5% to 10% of the patients, requiring surgery or transcatheter arterial embolization (TAE). TAE is now considered the first-line therapy for massive GI bleeding refractory to endoscopic management. GI endoscopists need to be familiar with indications, principles, outcomes, and complications of TAE, as well as embolic materials available. PMID:24143308

  8. Prediction of treatment refractoriness in ulcerative colitis and Crohn's disease--do we have reliable markers?

    PubMed

    Gelbmann, C M

    2000-05-01

    Treatment refractoriness is a severe problem in the management of patients with ulcerative colitis and Crohn's disease. Despite some promising new therapeutic approaches, corticosteroids are still the preferential primary treatment for moderate to severe Crohn's disease and of severe ulcerative colitis. However, clinical response to corticosteroids varies, and many patients are resistant to such treatment. Since corticosteroids have frequent and even severe side effects, and toxicity increases with chronic steroid intake, factors predictive of response to such treatment would be very helpful for decisions on further management of these patients. At least in severe attacks of ulcerative colitis, the consensus seems to be that a high frequency of bowel movements as well as a high C-reactive protein and low serum albumin recorded after a few days of intensive medical treatment are important signs for early prediction of treatment failure in the majority of the patients. In Crohn's disease thus far, data on predictive factors are conflicting. No reliable marker with sufficient predictive value for treatment refractoriness could be identified. This might be due to the tremendous heterogeneity of Crohn's disease with many clinical phenotypes, which requires subgroup analysis with sufficient numbers of patients. Corticosteroids as well as other immunomodulating and immunosuppressive medications interfere with the immune system, which plays a central role in the mediation of intestinal inflammation. Treatment refractoriness might have its origin in specific immunological peculiarities eventually reflected in abnormal immunological, biochemical, and clinical parameters. Further exploration of those parameters to predict treatment refractoriness in patients with ulcerative colitis or Crohn's disease is of great clinical importance for safe and efficient management of patients.

  9. Elevated VGKC-Complex Antibodies in a Boy with Fever-Induced Refractory Epileptic Encephalopathy in School-Age Children (FIRES)

    ERIC Educational Resources Information Center

    Illingworth, Marjorie A.; Hanrahan, Donncha; Anderson, Claire E.; O'Kane, Kathryn; Anderson, Jennifer; Casey, Maureen; de Sousa, Carlos; Cross, J. Helen; Wright, Sukvhir; Dale, Russell C.; Vincent, Angela; Kurian, Manju A.

    2011-01-01

    Fever-induced refractory epileptic encephalopathy in school-age children (FIRES) is a clinically recognized epileptic encephalopathy of unknown aetiology. Presentation in previously healthy children is characterized by febrile status epilepticus. A pharmacoresistant epilepsy ensues, occurring in parallel with dramatic cognitive decline and…

  10. [Extracorporeal photochemotherapy in therapy-refractory subacute lupus].

    PubMed

    Richard, M A; Saadallah, S; Lefevre, P; Poullin, P; Buscaylet, S; Grob, J J

    2002-01-01

    Extracorporeal photopheresis is a leukapheresis therapy that uses psoralen and ultraviolet A irradiation. We report the case of a woman with a refractory sub acute lupus which dramatically but transitionally responded to extracorporeal photopheresis. This women, born in 1960, developed erythematous and squamous patches located on face and neckline, associated with hyperpigmented and atrophic lesions on the arms and shoulders. Investigations confirmed the diagnosis of subacute lupus without systemic disease. All lesions progressed, despite all conventional therapies leading to major aesthetic prejudice. Extracorporeal photopheresis was initiated, and after two months, all lesions, including atrophic and healing lesions had regressed, but laboratory abnormalities did not change. Extracorporeal photopheresis was well tolerated. However, treatment was discontinued nine months later, since the cutaneous lesions relapsed. Extracorporeal photopheresis could be efficient in the treatment of cutaneous autoimmune diseases through several immunomodulatory mechanisms. Extracorporeal photopheresis is a potent alternative agent in the therapy of refractory dermatological diseases

  11. Relationship between cataract severity and socioeconomic status.

    PubMed

    Wesolosky, Jason D; Rudnisky, Christopher J

    2013-12-01

    To determine the relationship between cataract severity and socioeconomic status (SES). Retrospective, observational case series. A total of 1350 eyes underwent phacoemulsification cataract extraction by a single surgeon using an Alcon Infiniti system. Cataract severity was measured using phaco time in seconds. SES was measured using area-level aggregate census data: median income, education, proportion of common-law couples, and employment rate. Preoperative best corrected visual acuity was obtained and converted to logarithm of the minimum angle of resolution values. For patients undergoing bilateral surgery, the generalized estimating equation was used to account for the correlation between eyes. Univariate analyses were performed using simple regression, and multivariate analyses were performed to account for variables with significant relationships (p < 0.05) on univariate testing. Sensitivity analyses were performed to assess the effect of including patient age in the controlled analyses. Multivariate analyses demonstrated that cataracts were more severe when the median income was lower (p = 0.001) and the proportion of common-law couples living in a patient's community (p = 0.012) and the unemployment rate (p = 0.002) were higher. These associations persisted even when controlling for patient age. Patients of lower SES have more severe cataracts. Copyright © 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  12. 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

  13. 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

  14. The association between periodontal disease and seizure severity in refractory epilepsy patients.

    PubMed

    Costa, Andre L F; Yasuda, Clarissa Lin; Shibasaki, Wendel; Nahás-Scocate, Ana Carla Raphaelli; de Freitas, Claudio Fróes; Carvalho, Paulo Eduardo Guedes; Cendes, Fernando

    2014-03-01

    Periodontal diseases are common in most populations and affect people at all socioeconomic levels. Evidence suggests that patients with epilepsy actually have higher risks of dental disease and increased oral health needs, but the frequency and consequences of poor controlled seizures on dental and periodontal health have not been reported before. We aimed to assess the impact of seizure frequency on periodontal status and oral hygiene in a sample of epilepsy patients. One hundred and nine consecutive patients treated for epilepsy at the outpatient clinic of our University Hospital were invited to take part in an oral examination to determine their periodontal disease status, together with a control group. In addition, seizure frequency and use of medication were documented. In logistic regression model, patients were significantly more susceptible to bad oral hygiene, gingivitis and periodontitis that controls (p<0.001); seizure frequency was significantly related to bad oral hygiene (p=0.010), gingivitis (p<0.001) and periodontitis (p<0.001). Tooth brushing habits and presence of caries were associated with oral health in patients group. Our study found a significant positive correlation between periodontal disease and seizure severity. Epilepsy patients need to focus more on their oral health and quality of oral hygiene. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  15. Stem cell transplantation as rescue therapy for refractory Crohn's disease: a sytematic review.

    PubMed

    Labidi, Asma; Serghini, Meriem; Ben Mustapha, Nadia; Fekih, Monia; Boubaker, Jalel; Filali, Azza

    2014-11-01

    Crohn's disease is a chronic relapsing- remitting affection. It has a strong immunologic component which represent the target of standard therapies including immunosppressants and biological therapies. However, many patients remain refracory or intolerant to these therapies. The aim of this review is to determine the effects of stem cell transplantation in patients with refractory Crohn's disease. Systematic review of observational studies, clinical trials and case reports that focused on the effectiveness and safety of stem cell transplantation in patients with refractory Crohn's disease. Hematopoietic stem cell transplantation seems to be efficient in maintaining clinical and endoscopic remission in patients with Crohn's disease refractory or intolerant to current therapies. However, it has been associated to high morbidity and mortality due to chemotherapy. Mesenchymal stem cell transplantation could induce remission in patients with fistulising refractory Crohns disease with no severe side effects. Its impact on luminal Crohns disease is still controversial. Stem cell transplantation seems to hold promising in patients with refractory Crohn's disease. However, because of the high morbidity and mortality related to chemotherapy, hematopoietic stem cell transplantation should be used as last resort to control this disease. Effectiveness of mesenchymal stem cell transplantation in luminal Crohn's disease has yet to be proven.

  16. Successful treatment of refractory demodicosis and transient papules with a single dose of fluralaner in a dog with uncontrolled severe endocrine disease.

    PubMed

    Morita, Tatsushi; Momota, Yutaka; Mori, Akihiro; Oda, Hitomi; Ike, Kazunori; Sako, Toshinori

    2018-04-27

    A 12-year-old female Shih-Tzu with hyperadrenocorticism and hypothyroidism developed concurrent refractory generalized demodicosis that did not respond to doramectin treatment. Although amitraz treatment was effective, the dog developed severe diabetes, which resulted in the cessation of amitraz and trilostane. Attempts to control the diabetes were unsuccessful, and its hyperadrenocorticism was left untreated, leading to the recurrence of demodicosis. However, demodicosis went into complete remission with a single dose of fluralaner. Transient erythematous papules appeared on the trunk three days after the administration of fluralaner, but no other adverse reactions were noted. We demonstrated that fluralaner is a potent treatment for demodicosis, and skin eruptions are possible after the first dose of the drug.

  17. Management of refractory anti-phospholipid syndrome.

    PubMed

    Scoble, Tina; Wijetilleka, Sonali; Khamashta, Munther A

    2011-09-01

    Anti-phospholipid syndrome (APS) is an autoimmune prothrombotic disorder characterised by the predisposition to venous and/or arterial thrombosis and obstetric morbidity. Management of APS centres on attenuating the procoagulant state whilst balancing the risks of anticoagulant therapy. Cases of recurrent thromboses and obstetric complications occur despite optimum therapy. Alternative therapies for refractory cases are subject to disparity among clinicians due to the current lack of clinical evidence present. This review aims to address the current management strategies for refractory thrombotic and obstetric cases and future therapeutic interventions. The role and current clinical evidence of using long term low molecular weight heparin (LMWH) as an alternative to warfarin therapy for refractory thromboses is evaluated. Potential alternatives for thromboses including statins, hydroxychloroquine, Rituximab are reviewed as well as the additional avenues to target in the future as the pathogenic mechanisms of APS are unveiled. The optimal management for refractory obstetric APS cases is subject to controversy. This review focuses and assesses the current evidence for the uses of low dose prednisolone, intravenous immunoglobulin and hydroxycholoroquine in obstetric cases. The treatment modalities for the management of refractory APS require further clinical evidence. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2013-10-01

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

  19. Optimization of the Technological Synthesis of Refractory Compounds

    NASA Astrophysics Data System (ADS)

    Gaidar, S. M.; Karelina, M. Yu.; Prikhod'ko, V. M.; Volkov, A. A.

    2017-12-01

    The results of experimental studies, which are related to the regulation of the fractional composition of refractory compounds by roll milling in using controlled roll opening and unbalanced peripheral speeds of rollers, are reported. The content of prepared fine, middle, and coarse fractions is within 50-80%; in this case, the milling time of synthesis products is less than the time of ball milling by an order of magnitude. The application of roll milling for refining the products of self-propagating high-temperature synthesis can be most efficient in using together with heat-generating reactor to solve the main problem of self-propagating synthesis (SHS), which is a problem for recent several decades (the problem is the creation of intense automated production of refractory compounds in using continuous manufacturing cycle within a energotechnological system with the recovery of a great quantity of heat released during SHS).

  20. REFRACTORY COATING FOR GRAPHITE MOLDS

    DOEpatents

    Stoddard, S.D.

    1958-06-24

    Refractory coating for graphite molds used in the casting of uranium is described. The coating is an alumino-silicate refractory composition which may be used as a mold surface in solid form or as a coating applied to the graphite mold. The composition consists of a mixture of ball clay, kaolin, alumina cement, alumina, water, sodium silicate, and sodium carbonate.

  1. Efficacy of Pregabalin in Childhood Refractory Partial Seizure

    PubMed Central

    Zamani, Gholamreza; Tavasoli, Alireza; Zare-Shahabadi, Ameneh; Rezaei, Nima; Ahmadvand, Alireza

    2014-01-01

    Objective: About one third of partial seizures are refractory to treatment. Several anticonvulsant drugs have entered the market in recent decades but concerns about intolerance, drug interactions, and the safety of the drug are notable. One of these new anticonvulsants is pregabalin, a safe drug with almost no interaction with other antiepileptic drugs. Methods: In this open label clinical trial study, pregabalin was used for evaluation of its efficacy on reducing seizure frequency in 29 children suffering from refractory partial seizures. Average daily and weekly seizure frequency of the patients was recorded during a 6-week period (baseline period). Then, during a period of 2 weeks (titration period), pregabalin was started with a dose of 25-75 mg/d, using method of flexible dose, and was brought to maximum dose of drug that was intended in this study (450 mg/d) based on clinical response of the patients and seizure frequency. Then the patients were given the drug for 12 weeks and the average frequency of daily and weekly seizures were recorded again (treatment period). Findings : Reduction in seizure frequency in this study was 36% and the responder rate or number of patients who gained more than 50% reduction in seizure frequency was 51.7%. Conclusion: This study showed that pregabalin can be used with safety and an acceptable efficacy in treatment of childhood refractory partial seizures. PMID:25793053

  2. Refractory lining for electrochemical cell

    DOEpatents

    Blander, Milton; Cook, Glenn M.

    1987-01-01

    Apparatus for processing a metallic fluid containing iron oxide, container for a molten metal including an electrically conductive refractory disposed for contact with the molten metal which contains iron oxide, an electrolyte in the form of a basic slag on top of the molten metal, an electrode in the container in contcat with the slag electrically separated from the refractory, and means for establishing a voltage across the refractory and the electrode to reduce iron oxide to iron at the surface of the refractory in contact with the iron oxide containing fluid. A process is disclosed for refining an iron product containing not more than about 10% by weight oxygen and not more than about 10% by weight sulfur, comprising providing an electrolyte of a slag containing one or more of calcium oxide, magnesium oxide, silica or alumina, providing a cathode of the iron product in contact with the electrolyte, providing an anode in contact with the electrolyte electrically separated from the cathode, and operating an electrochemical cell formed by the anode, the cathode and the electrolyte to separate oxygen or sulfur present in the iron product therefrom.

  3. Does semiology of status epilepticus have an impact on treatment response and outcome?

    PubMed

    Baysal-Kirac, Leyla; Feddersen, Berend; Einhellig, Marion; Rémi, Jan; Noachtar, Soheyl

    2018-06-01

    This study investigated whether there is an association between semiology of status epilepticus (SE) and response to treatment and outcome. Two hundred ninety-eight consecutive adult patients (160 females, 138 males) with SE at the University of Munich Hospital were prospectively enrolled. Mean age was 63.2±17.5 (18-97) years. Patient demographics, SE semiology and electroencephalography (EEG) findings, etiology, duration of SE, treatment, and outcome measures were investigated. Status epilepticus semiology was classified according to a semiological status classification. Patient's short-term outcome was determined by Glasgow Outcome Scale (GOS). The most frequent SE type was nonconvulsive SE (NCSE) (39.2%), mostly associated with cerebrovascular etiology (46.6%). A potentially fatal etiology was found in 34.8% of the patients. More than half (60.7%) of the patients had poor short-term outcome (GOS≤3) with an overall mortality of 12.4%. SE was refractory to treatment in 21.5% of the patients. Older age, potentially fatal etiology, systemic infections, NCSE in coma, refractory SE, treatment with anesthetics, long SE duration (>24h), low Glasgow Coma Scale (GCS) (≤8) at onset, and high Status Epilepticus Severity Score (STESS-3) (≥3) were associated with poor short-term outcome and death (p<0.05). Potentially fatal etiology and low GCS were the strongest predictors of poor outcome (Exp [b]: 4.74 and 4.10 respectively, p<0.05). Status epilepticus semiology has no independent association with outcome, but potentially fatal etiology and low GCS were strong predictive factors for poor short-term outcome of SE. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Exogenous ACE2 Expression Allows Refractory Cell Lines To Support Severe Acute Respiratory Syndrome Coronavirus Replication

    PubMed Central

    Mossel, Eric C.; Huang, Cheng; Narayanan, Krishna; Makino, Shinji; Tesh, Robert B.; Peters, C. J.

    2005-01-01

    Of 30 cell lines and primary cells examined, productive severe acute respiratory syndrome coronavirus (Urbani strain) (SARS-CoV) infection after low-multiplicity inoculation was detected in only six: three African green monkey kidney epithelial cell lines (Vero, Vero E6, and MA104), a human colon epithelial line (CaCo-2), a porcine kidney epithelial line [PK(15)], and mink lung epithelial cells (Mv 1 Lu). SARS-CoV produced a lytic infection in Vero, Vero E6, and MA104 cells, but there was no visible cytopathic effect in Caco-2, Mv 1 Lu, or PK(15) cells. Multistep growth kinetics were identical in Vero E6 and MA104 cells, with maximum titer reached 24 h postinoculation (hpi). Virus titer was maximal 96 hpi in CaCo-2 cells, and virus was continually produced from infected CaCo-2 cells for at least 6 weeks after infection. CaCo-2 was the only human cell type of 13 tested that supported efficient SARS-CoV replication. Expression of the SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2), resulted in SARS-CoV replication in all refractory cell lines examined. Titers achieved were variable and dependent upon the method of ACE2 expression. PMID:15731278

  5. Treatment of Generalized Convulsive Status Epilepticus in Pediatric Patients

    PubMed Central

    Alford, Elizabeth L.; Wheless, James W.

    2015-01-01

    Generalized convulsive status epilepticus (GCSE) is one of the most common neurologic emergencies and can be associated with significant morbidity and mortality if not treated promptly and aggressively. Management of GCSE is staged and generally involves the use of life support measures, identification and management of underlying causes, and rapid initiation of anticonvulsants. The purpose of this article is to review and evaluate published reports regarding the treatment of impending, established, refractory, and super-refractory GCSE in pediatric patients. PMID:26380568

  6. 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.

  7. 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.

  8. Refractory Materials for Flame Deflector Protection System Corrosion Control: Similar Industries and/or Launch Facilities Survey

    NASA Technical Reports Server (NTRS)

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

    2009-01-01

    A trade study and litera ture survey of refractory materials (fi rebrick. refractory concrete. and si licone and epoxy ablatives) were conducted to identify candidate replacement materials for Launch Complexes 39A and 398 at Kennedy Space Center (KSC). In addition, site vis its and in terviews with industry expens and vendors of refractory materials were conducted. As a result of the si te visits and interviews, several products were identified for launch applications. Firebrick is costly to procure and install and was not used in the si tes studied. Refractory concrete is gunnable. adheres well. and costs less 10 install. Martyte. a ceramic fi lled epoxy. can protect structural stccl but is costly. difficullto apply. and incompatible with silicone ablatives. Havanex, a phenolic ablative material, is easy to apply but is costly and requires frequent replacement. Silicone ablatives are ineJ[pensive, easy to apply. and perl'onn well outside of direct rocket impingement areas. but refractory concrete and epoxy ablatives provide better protection against direcl rocket exhaust. None of the prodUCIS in this trade study can be considered a panacea for these KSC launch complexes. but the refractory products. individually or in combination, may be considered for use provided the appropriate testing requirements and specifications are met.

  9. Refractory hypoglycaemia in a dog infected with Trypanosoma congolense

    PubMed Central

    Deschamps, Jack-Yves; Desquesnes, Marc; Dorso, Laetitia; Ravel, Sophie; Bossard, Géraldine; Charbonneau, Morgane; Garand, Annabelle; Roux, Françoise A.

    2016-01-01

    A 20 kg German shepherd dog was presented to a French veterinary teaching hospital for seizures and hyperthermia. The dog had returned 1 month previously from a six-month stay in Senegal and sub-Saharan Africa. Biochemistry and haematology showed severe hypoglycaemia (0.12 g/L), anaemia and thrombocytopenia. Despite administration of large amounts of glucose (30 mL of 30% glucose IV and 10 mL of 70% sucrose by gavage tube hourly), 26 consecutive blood glucose measurements were below 0.25 g/L (except one). Routine cytological examination of blood smears revealed numerous free extracytoplasmic protozoa consistent with Trypanosoma congolense. PCR confirmed a Trypanosoma congolense forest-type infection. Treatment consisted of six injections of pentamidine at 48-hour intervals. Trypanosomes had disappeared from the blood smears four days following the first injection. Clinical improvement was correlated with the normalization of laboratory values. The infection relapsed twice and the dog was treated again; clinical signs and parasites disappeared and the dog was considered cured; however, 6 years after this incident, serological examination by ELISA T. congolense was positive. The status of this dog (infected or non-infected) remains unclear. Hypoglycaemia was the most notable clinical feature in this case. It was spectacular in its severity and in its refractory nature; glucose administration seemed only to feed the trypanosomes, indicating that treatment of hypoglycaemia may in fact have been detrimental. PMID:26795063

  10. Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer

    PubMed Central

    Sayal, Karen; Gounaris, Ioannis; Basu, Bristi; Freeman, Sue; Moyle, Penny; Hosking, Karen; Iddawela, Mahesh; Jimenez-Linan, Mercedes; Abraham, Jean; Brenton, James; Hatcher, Helen; Earl, Helena; Parkinson, Christine

    2015-01-01

    Objective Primary platinum-resistant epithelial ovarian cancer (EOC) is an area of unmet medical need. There is limited evidence from small studies that platinum-based combinations can overcome “resistance” in a proportion of patients. We investigated the efficacy and toxicity of platinum-based combination chemotherapy in the platinum-resistant and platinum-refractory setting. Methods Epirubicin, cisplatin, and capecitabine (ECX) combination chemotherapy was used at our institution for the treatment of relapsed EOC. From the institutional database, we identified all patients with primary platinum-refractory or platinum-resistant relapse treated with ECX as second-line therapy between 2001 and 2012. We extracted demographic, clinical, treatment, and toxicity data and outcomes. We used logistic and Cox regression models to identify predictors of response and survival respectively. Results Thirty-four 34 patients (8 refractory, 26 resistant) were treated with ECX. Response Evaluation Criteria In Solid Tumors (RECIST) response rate was 45%, median progression-free survival (PFS) was 6.4 months, and overall survival (OS) was 10.6 months. Platinum-resistant patients had better outcomes than did platinum-refractory patients (response rate, 54% vs 0%, P = 0.047; PFS 7.2 vs 1.8 months, P < 0.0001; OS 14.4 vs 3 months, P < 0.001). In regression models, time to progression after first-line treatment and platinum-refractory status were the strongest predictors of response and PFS or OS, respectively. Patients with time to progression after first-line treatment longer than 3 months showed PFS and OS of 7.9 and 14.7 months, respectively. Toxicity was manageable, with only 13% of cycles administered at reduced doses. Conclusions Epirubicin, cisplatin, and capecitabine seems to be active in platinum-resistant relapsed EOC with manageable toxicity. Further prospective investigation of platinum-anthracycline combinations is warranted in patients who relapse 3 to 6 months after

  11. Successful management of refractory cases of canine demodicosis with homeopathy medicine Graphitis.

    PubMed

    Ranjan, Rakesh; Dua, Kirti; Turkar, Sujata; Singh, Harkirat; Singla, L D

    2014-12-01

    Canine demodicosis is a refractory skin disease caused by excessive proliferation of mite Demodex canis. Despite availability of several treatment options, the disease poses a great challenge to clinicians for its long term management as some drugs may be ineffective or toxic. Present report describes successful treatment of two refractory cases of canine demodicosis using homeopathy medicine. After oral administration of Graphitis 200 C two drops once daily for 2 months, complete cure from the disease was observed. No adverse health effects of the medication were recorded during the treatment. Thus, it may be concluded that homeopathy medicine may be used safely for long-term management of canine demodicosis.

  12. 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.

  13. Properties of Refractory Concrete in Tension and Compression

    NASA Technical Reports Server (NTRS)

    Sampson, Jeffrey

    2009-01-01

    Refractory concrete on the LC-39A Flame Deflector has been damaged during multiple Space Shuttle launches (e.g. STS-124, STS-126, STS-119, and STS-125, STS-127). These events have prompted a better understanding of the system via an analytical model of the Flame Deflector assembly to include the Fondu Fyre refractory concrete. This model requires test data inputs of the refractory concrete's mechanical properties, which include stress versus strain curves in tension and compression, modulus of elasticity, and Poisson's ratio. Sections of Fondu Fyre refractory concrete removed from the LC-39A Flame Deflector were provided for this testing.

  14. Traditional and Alternative Therapies for Refractory Angina.

    PubMed

    Kocyigit, Duygu; Gurses, Kadri Murat; Yalcin, Muhammed Ulvi; Tokgozoglu, Lale

    2017-01-01

    Refractory angina (RFA) is an unfavourable condition that is characterized with persistent angina due to reversible myocardial ischemia in patients with coronary artery disease that remains uncontrollable despite an optimal combination of pharmacological agents and revascularization. Despite significant advances in revascularization techniques and agents used in pharmacological therapy, there is still a significant population suffering from RFA and the global prevalence is even increasing. Anti- anginal treatment and secondary risk-factor modification are the traditional approaches for this group of patients. Furthermore, now there is still a large number of alternative treatment options. In order to review traditional and alternative treatment strategies in patients with RFA, we searched Pubmed for articles in English using the search terms "pharmacological therapy, refractory angina", "alternative therapy, refractory angina" between inception to June 2016. We also went through separately for each alternative treatment modality on Pubmed. To identify further articles, we handsearched related citations in review articles and commentaries. We also included data from the European Society of Cardiology (2013), and the Canadian Society of Cardiology/ Canadian Pain Society (2012) guidelines. Data show that besides traditional pharmacological agents, such as nitrates, beta- blockers or calcium channel blockers, novel antiischemic drugs and if symptoms persist, several non- invasive and/ or invasive alternative strategies may be considered. Impact of some pharmacological agents, such as rho- kinase inhibitors, and novel alternative treatment modalities, such as coronary sinus reducers, stem cell therapy, gene and protein therapy, on outcomes are still under investigation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Review of status and potential of tungsten-wire: Superalloy composites for advanced gas turbine engine blades

    NASA Technical Reports Server (NTRS)

    Signorelli, R. A.

    1972-01-01

    The current status of development of refractory-wire-superalloy composites and the potential for their application to turbine blades in land-based power generation and advanced aircraft engines are reviewed. The data indicate that refractory-wire-superalloy composites have application as turbine blades at temperatures of 2200 F and above.

  16. Use of a pediatric oxygenator integrated in a veno-venous hemofiltration circuit to remove CO2: a case report in a severe burn patient with refractory hypercapnia.

    PubMed

    Rousseau, Anne-Françoise; Damas, Pierre; Renwart, Ludovic; Amand, Théo; Erpicum, Marie; Morimont, Philippe; Dubois, Bernard; Massion, Paul B

    2014-11-01

    Acute respiratory distress syndrome management is currently based on lung protective ventilation. Such strategy may lead to hypercapnic acidosis. We report a case of refractory hypercapnia in a severe burn adult, treated with simplified veno-venous extracorporeal carbon dioxide removal technique. We integrated a pediatric oxygenator in a continuous veno-venous hemofiltration circuit. This technique, used during at least 96h, was feasible, sure and efficient with carbon dioxide removal rate up to 32%. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

  17. Modification of surface properties of copper-refractory metal alloys

    DOEpatents

    Verhoeven, John D.; Gibson, Edwin D.

    1993-10-12

    The surface properties of copper-refractory metal (CU-RF) alloy bodies are modified by heat treatments which cause the refractory metal to form a coating on the exterior surfaces of the alloy body. The alloys have a copper matrix with particles or dendrites of the refractory metal dispersed therein, which may be niobium, vanadium, tantalum, chromium, molybdenum, or tungsten. The surface properties of the bodies are changed from those of copper to that of the refractory metal.

  18. 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.

  19. 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.

  20. Oral Alitretinoin in the Treatment of Severe Refractory Chronic Hand Eczema in the Spanish National Health System: Description and Analysis of Current Clinical Practice.

    PubMed

    Urrutia, S; Roustan, G; Plazas, M J; Armengol, S; Paz, S; Lizan, L

    2016-03-01

    Hand eczema affects nearly 10% of the population. The condition becomes severe and chronic in 5% to 7% of cases and is refractory to topical corticosteroids in 2% to 4%. This study aimed to describe the current use of oral alitretinoin in treating Spanish national health system patients with hand eczema that is refractory to potent topical corticosteroids. Observational, descriptive, exploratory, cross-sectional study based on the retrospective analysis of records for patients with hand eczema treated with alitretinoin in the Spanish national health system. We reviewed the records for 62 patients in 13 hospitals in 5 different administrative areas (autonomous communities) of Spain. Alitretinoin was usually used at a dosage of 30mg/d. In most cases the physician judged the clinical response to be satisfactory after a single cycle. The recorded adverse effects were foreseeable and of the type reported for systemic retinoids. The dermatologists agreed that the clinical benefits achieved with alitretinoin favored adherence to treatment and an early return to work. The results show that oral alitretinoin is being used according to established recommendations and that response is good, with few adverse effects. The dermatologists agreed that the benefits favored adherence and improved the patients' health related quality of life. Copyright © 2015 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

  1. The management of Convulsive Refractory Status Epilepticus in adults in the UK: No consistency in practice and little access to continuous EEG monitoring.

    PubMed

    Patel, Mitesh; Bagary, Manny; McCorry, Dougall

    2015-01-01

    Convulsive Status Epilepticus (CSE) is a common neurological emergency with patients presenting with prolonged epileptic activity. Sub-optimal management is coupled with high morbidity and mortality. Continuous electroencephalogram (EEG) monitoring is considered essential by the National Institute for Health and Care Excellence (NICE) in the management of Convulsive Refractory Status Epilepticus (CRSE). The aim of this research was to determine current clinical practice in the management of CRSE amongst adults in intensive care units (ICU) in the UK and establish if the use of a standardised protocol requires re-enforcement within trusts. 75 randomly selected UK NHS Trusts were contacted and asked to complete a questionnaire in addition to providing their protocol for CRSE management in ICU. 55 (73%) trusts responded. While 31 (56% of responders) had a protocol available in ICU for early stages of CSE, just 21 (38%) trusts had specific guidelines if CRSE occurred. Only 23 (42%) trusts involved neurologists at any stage of management and just 18 (33%) have access to continuous EEG monitoring. This study identifies significant inconsistency in the management of CSE in ICU's across the UK. A minority of ICU units have a protocol for CRSE or access to continuous EEG monitoring despite it being considered fundamental for management and supported by NICE guidance. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  2. 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.

  3. Refractory Degradation by Slag Attack in Coal Gasification

    DTIC Science & Technology

    2009-02-01

    REFRACTORY DEGRADATION BY SLAG ATTACK IN COAL GASIFICATION Jinichiro Nakano 1,2 , Sridhar Seetharaman 1,2 , James Bennett 3 , Kyei-Sing...and two synthetic slags (coal and petcoke). Pulverized slag samples were placed at specific microstructure locations on refractory substrates and...heated to 1500 ºC at log(Po2) = -9, using a high-speed heating chamber. Cross-sections of the slag /refractory interface indicated unique slag

  4. Does Narcolepsy Symptom Severity Vary According to HLA-DQB1*0602 Allele Status?

    PubMed Central

    Watson, Nathaniel F.; Ton, Thanh G.N.; Koepsell, Thomas D.; Gersuk, Vivian H.; Longstreth, W.T.

    2010-01-01

    Study Objectives: To investigate associations between HLA-DQB1*0602 allele status and measures of narcolepsy symptom severity. Design: Cross-sectional study of population-based narcolepsy patients. Setting: King County, Washington. Participants: All prevalent cases (n = 279) of physician-diagnosed narcolepsy ascertained from 2001-2005. Interventions: N/A Measurements: Narcolepsy diagnosis was based on cataplexy status, diagnostic sleep study results, and chart review. The number of HLA-DQB1 alleles was determined from buccal genomic DNA. Symptom severity instruments included the Epworth Sleepiness Scale (ESS), the Ullanlinna Narcolepsy Scale (UNS), age of symptom onset, subjective sleep latency and duration, and various clinical sleep parameters. We used linear regression adjusted for African American race and an extended chi-square test of trend to assess relationships across ordered groups defined by allele number (0, 1, or 2). Results: Narcolepsy patients were 63% female and 82% Caucasian, with a mean age of 47.6 years (SD = 17.1). One hundred forty-one (51%) patients had no DQB1*0602 alleles; 117 (42%) had one; and 21 (7%) had two. In the complete narcolepsy sample after adjustment for African American race, we observed a linear relationship between HLA-DQB1*0602 frequency and sleepiness as defined by the ESS (P < 0.01), narcolepsy severity as defined by UNS (P < 0.001), age of symptom onset (P < 0.05), and sleep latency (P < 0.001). In univariate analyses, HLA-DQB1*0602 frequency was also associated with napping (P < 0.05) and increased car and work accidents or near accidents (both P < 0.01). Habitual sleep duration was not associated with HLA status. These race-adjusted associations remained for the ESS (P < 0.05), UNS (P < 0.01), and sleep latency (P < 0.001) when restricting to narcolepsy with cataplexy. Conclusions: Narcolepsy symptom severity varies in a linear manner according to HLA-DQB1*0602 allele status. These findings support the notion that HLA

  5. 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.

  6. Propofol versus thiopental sodium for the treatment of refractory status epilepticus.

    PubMed

    Prabhakar, Hemanshu; Kalaivani, Mani

    2015-06-25

    This is an updated version of the original Cochrane review published in Issue 8, 2012.Failure to respond to antiepileptic drugs in patients with uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is a substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome. To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (26 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 2, February 2015) and MEDLINE (1946 to 26 March 2015). We also searched ClinicalTrials.gov (26 March 2015), the South Asian Database of Controlled Clinical Trials and IndMED (a bibliographic database of Indian Medical Journals). All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol in patients of any age and gender. Two review authors screened the search results and reviewed the abstracts of relevant and eligible trials before retrieving the full-text publications. One study with a total of 24 participants was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE receiving either propofol or thiopental sodium for the control of seizure activity. This study cannot be considered of high methodological quality. This study was terminated early due to recruitment problems. This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. Days of mechanical ventilation were more in patients

  7. Distinguishing in-hospital and out-of-hospital status epilepticus: clinical implications from a 10-year cohort study.

    PubMed

    Sutter, R; Semmlack, S; Spiegel, R; Tisljar, K; Rüegg, S; Marsch, S

    2017-09-01

    The aim was to determine differences of clinical, treatment and outcome characteristics between patients with in-hospital and out-of-hospital status epilepticus (SE). From 2005 to 2014, clinical data were assessed in adults with SE treated in an academic medical care centre. Clinical characteristics, treatment and outcomes were compared between patients with in-hospital and out-of-hospital SE. Amongst 352 patients, 213 were admitted with SE and 139 developed in-hospital SE. Patients with in-hospital SE had more acute/fatal aetiologies (60% vs. 35%, P < 0.001), fewer previous seizures (33% vs. 50%, P = 0.002), a higher median Charlson Comorbidity Index (3 vs. 2, P < 0.001), longer median SE duration (1 vs. 0.5 days, P = 0.001), more refractory SE (52% vs. 39%, P = 0.022), less return to functional baseline (38% vs. 54%, P = 0.006) and increased mortality (29% vs. 19%, P = 0.001). Whilst in multivariable analyses an increasing Status Epilepticus Severity Score (STESS) was an independent predictor for death in both groups, increased Charlson Comorbidity Index and treatment refractory SE were associated with death only in patients with in-hospital SE. Continuous anaesthesia for refractory SE was associated with increased mortality only in patients with out-of-hospital SE. The area under the receiver operating curve was 0.717 for prediction of death by STESS in patients with in-hospital SE and 0.811 in patients with out-of-hospital SE. Patients with in-hospital SE had more fatal aetiologies and comorbidities, refractory SE, less return to functional baseline, and increased mortality compared to patients with out-of-hospital SE. Whilst the STESS was a robust predictor for death in both groups, the association between continuous anaesthesia and death was limited to out-of-hospital SE. © 2017 EAN.

  8. 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

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

    PubMed Central

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

    2016-01-01

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

  10. 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.

  11. Medical versus surgical treatment for refractory or recurrent peptic ulcer.

    PubMed

    Gurusamy, Kurinchi Selvan; Pallari, Elena

    2016-03-29

    Refractory peptic ulcers are ulcers in the stomach or duodenum that do not heal after eight to 12 weeks of medical treatment or those that are associated with complications despite medical treatment. Recurrent peptic ulcers are peptic ulcers that recur after healing of the ulcer. Given the number of deaths due to peptic ulcer-related complications and the long-term complications of medical treatment (increased incidence of fracture), it is unclear whether medical or surgical intervention is the better treatment option in people with recurrent or refractory peptic ulcers. To assess the benefits and harms of medical versus surgical treatment for people with recurrent or refractory peptic ulcer. We searched the specialised register of the Cochrane Upper GI and Pancreatic Diseases group, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and trials registers until September 2015 to identify randomised trials and non-randomised studies, using search strategies. We also searched the references of included studies to identify further studies. We considered randomised controlled trials and non-randomised studies comparing medical treatment with surgical treatment in people with refractory or recurrent peptic ulcer, irrespective of language, blinding, or publication status for inclusion in the review. Two review authors independently identified trials and extracted data. We planned to calculate the risk ratio, mean difference, standardised mean difference, or hazard ratio with 95% confidence intervals using both fixed-effect and random-effects models with Review Manager 5 based on intention-to-treat analysis. We included only one non-randomised study published 30 years ago in the review. This study included 77 participants who had gastric ulcer and in whom medical therapy (histamine H2 receptor blockers, antacids, and diet) had failed after an average duration of treatment of 29 months. The

  12. A case of refractory chronic neutrophilic pustular folliculitis treated with adalimumab.

    PubMed

    Sand, Freja Laerke; Thomsen, Simon Francis

    2015-01-01

    Neutrophilic folliculitis is an often overlooked chronic condition characterized by a monomorphic eruption of "sterile" papulopustules. Neutrophilic folliculitis is often refractory to conventional treatment with topical and systemic antibiotics or isotretinoin. We report a case of severe pustular neutrophilic folliculitis successfully treated with the tumor necrosis factor-alpha inhibitor adalimumab. © 2014 Wiley Periodicals, Inc.

  13. Recent status scores for version 6 of the Addiction Severity Index (ASI-6).

    PubMed

    Cacciola, John S; Alterman, Arthur I; Habing, Brian; McLellan, A Thomas

    2011-09-01

    To describe the derivation of recent status scores (RSSs) for version 6 of the Addiction Severity Index (ASI-6). 118 ASI-6 recent status items were subjected to nonparametric item response theory (NIRT) analyses followed by confirmatory factor analysis (CFA). Generalizability and concurrent validity of the derived scores were determined. A total of 607 recent admissions to variety of substance abuse treatment programs constituted the derivation sample; a subset (n = 252) comprised the validity sample. The ASI-6 interview and a validity battery of primarily self-report questionnaires that included at least one measure corresponding to each of the seven ASI domains were administered. Nine summary scales describing recent status that achieved or approached both high scalability and reliability were derived; one scale for each of six areas (medical, employment/finances, alcohol, drug, legal, psychiatric) and three scales for the family/social area. Intercorrelations among the RSSs also supported the multi-dimensionality of the ASI-6. Concurrent validity analyses yielded strong evidence supporting the validity of six of the RSSs (medical, alcohol, drug, employment, family/social problems, psychiatric). Evidence was weaker for the legal, family/social support and child problems RSSs. Generalizability analyses of the scales to males versus females and whites versus blacks supported the comparability of the findings, with slight exceptions. The psychometric analyses to derive Addiction Severity Index version 6 recent status scores support the multi-dimensionality of the Addiction Severity Index version 6 (i.e. the relative independence of different life functioning areas), consistent with research on earlier editions of the instrument. In general, the Addiction Severity Index version 6 scales demonstrate acceptable scalability, reliability and concurrent validity. While questions remain about the generalizability of some scales to population subgroups, the overall findings

  14. Fully covered self-expanding metallic stent placement for benign refractory esophageal strictures.

    PubMed

    Kahalekar, Vinit; Gupta, Deepak Trilokinath; Bhatt, Pratin; Shukla, Akash; Bhatia, Shobna

    2017-05-01

    Treatment options for benign refractory esophageal stricture are limited. We retrospectively analyzed data of 11 patients who underwent fully covered self-expanding metallic stent (FC-SEMS) placement for refractory benign esophageal stricture at our institute. Refractory benign esophageal stricture was defined as inability to dilate a stricture to a diameter of 14 mm after a minimum of five sessions at 2-week intervals or inability to maintain diameter of 14 mm for at least 4 weeks. Eleven patients with refractory benign esophageal stricture (corrosive-6, peptic-3, and post-sclerotherapy-2) underwent FC-SEMS placement. The stent was removed after 4-6 weeks as per manufacturer's recommendation. Patients were followed up for 1 year. Three patients with peptic strictures [length of stricture 2, 3, and 3 cm] and two patients with post-sclerotherapy stricture [length 2 and 1.5 cm] had complete response. Two of 6 patients with corrosive stricture (10 cm, 12 cm) developed recurrence of symptoms within 1 month of stent removal, and two after 2 months (8 cm, 3 cm). One patient with corrosive stricture (6 cm) had recurrence after 6 months, and responded to single session of dilatation. One patient with corrosive stricture was asymptomatic for last 12 months. Four stents were migrated. Four patients developed severe retrosternal pain following stent placement, which was managed with analgesics. There were no serious adverse events after placement of stent and removal of stent. Fully covered SEMS is safe and effective for refractory benign non-corrosive esophageal strictures.

  15. Cyclodiode photocoagulation for refractory glaucoma after penetrating keratoplasty.

    PubMed

    Shah, P; Lee, G A; Kirwan, J K; Bunce, C; Bloom, P A; Ficker, L A; Khaw, P T

    2001-11-01

    This study analyzes the results of intraocular pressure (IOP) reduction by contact diode cycloablation (cyclodiode) in cases of refractory glaucoma after penetrating keratoplasty. Retrospective noncomparative, interventional case series. Twenty-eight eyes in 28 patients attending the Moorfields Eye Hospital. Cyclodiode (40 applications x 1.5 W x 1.5 seconds over 270-300 degrees ) was used to control the IOP in refractory glaucoma after penetrating keratoplasty. Postoperative IOP, graft status, visual acuity, and number of antiglaucoma medications were recorded after cyclodiode treatment. Cyclodiode resulted in a reduction of IOP from a median of 33 mmHg (interquartile range [28, 40.5]) to a median of 15 mmHg (interquartile range [12, 20.5]). Most patients had a significant lowering in IOP with a median reduction of 16 mmHg (interquartile range [12, 25]; P < 0.0001). IOPs of 6 to 21 mmHg were achieved in 22 patients (79%). Sixteen patients (57%) required more than one treatment with cyclodiode to control the IOP, with three patients (11%) requiring three treatments and two patients (7%) requiring four treatments. Visual acuity improved (> two Snellen lines of acuity) in three patients (11%) and remained the same (+/- one Snellen line) in 17 patients (61%). The mean number of antiglaucoma medications before cycloablation was 2.6 and was 1.8 after treatment (P < 0.001). Of the 19 patients (68%) with originally clear grafts, three grafts (16%) developed opacification. One patient (4%), with a history of nanophthalmos and recurrent uveal effusion, had delayed hypotony (IOP < 6 mmHg) occurring 46 months after the diode treatment. All patients had at least 6 months follow-up. These patients have often undergone multiple previous complicated ocular interventions and are often not suitable for filtration surgery. Reduction of IOP with maintenance of visual acuity and a good safety profile was achieved in most patients in this study but may require multiple treatments. We

  16. 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.

  17. 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.

  18. Development of a patient decision aid for people with refractory angina: protocol for a three-phase pilot study

    PubMed Central

    2014-01-01

    Background Refractory angina is a severe chronic disease, defined as angina which cannot be controlled by usual treatments for heart disease. This disease is frightening, debilitating, and difficult to manage. Many people suffering refractory have inadequate pain relief, continually revisit emergency departments for help, undergo repeated cardiac investigations, and struggle with obtaining appropriate care. There is no clear framework to help people understand the risks and benefits of available treatment options in Canada. Some treatments for refractory angina are invasive, while others are not covered by provincial health insurance plans. Effective care for refractory angina sufferers in Canada is critically underdeveloped; it is important that healthcare professionals and refractory angina sufferers alike understand the treatment options and their implications. This proposal builds on the recent Canadian practice guidelines for the management of refractory angina. We propose to develop a decision support tool in order to help people suffering from refractory angina make well-informed decisions about their healthcare and reduce their uncertainty about treatment options. Methods This project will be conducted in three phases: a) development of the support tool with input from clinical experts, the Canadian refractory angina guidelines, and people living with refractory angina, b) pilot testing of the usability of the tool, and c) formal preliminary evaluation of the effectiveness of the support tool to help people make informed decisions about treatment options. Discussion A decision support tool for refractory angina is needed and the available data suggest that by developing such a tool, we may be able to help refractory angina sufferers better understand their condition and the effectiveness of available treatment options (in their respective clinical settings) as well as their implications (e.g. risks vs. benefits). By virtue of this tool, we may also be able

  19. Treatment of Convulsive Status Epilepticus.

    PubMed

    Grover, Eric H; Nazzal, Yara; Hirsch, Lawrence J

    2016-03-01

    Convulsive status epilepticus (CSE) is a medical emergency with an associated high mortality and morbidity. It is defined as a convulsive seizure lasting more than 5 min or consecutive seizures without recovery of consciousness. Successful management of CSE depends on rapid administration of adequate doses of anti-epileptic drugs (AEDs). The exact choice of AED is less important than rapid treatment and early consideration of reversible etiologies. Current guidelines recommend the use of benzodiazepines (BNZ) as first-line treatment in CSE. Midazolam is effective and safe in the pre-hospital or home setting when administered intramuscularly (best evidence), buccally, or nasally (the latter two possibly faster acting than intramuscular (IM) but with lower levels of evidence). Regular use of home rescue medications such as nasal/buccal midazolam by patients and caregivers for prolonged seizures and seizure clusters may prevent SE, prevent emergency room visits, improve quality of life, and lower health care costs. Traditionally, phenytoin is the preferred second-line agent in treating CSE, but it is limited by hypotension, potential arrhythmias, allergies, drug interactions, and problems from extravasation. Intravenous valproate is an effective and safe alternative to phenytoin. Valproate is loaded intravenously rapidly and more safely than phenytoin, has broad-spectrum efficacy, and fewer acute side effects. Levetiracetam and lacosamide are well tolerated intravenous (IV) AEDs with fewer interactions, allergies, and contraindications, making them potentially attractive as second- or third-line agents in treating CSE. However, data are limited on their efficacy in CSE. Ketamine is probably effective in treating refractory CSE (RCSE), and may warrant earlier use; this requires further study. CSE should be treated aggressively and quickly, with confirmation of treatment success with epileptiform electroencephalographic (EEG), as a transition to non-convulsive status

  20. The Pluripotent Stem-Cell Marker Alkaline Phosphatase is Highly Expressed in Refractory Glioblastoma with DNA Hypomethylation.

    PubMed

    Iwadate, Yasuo; Suganami, Akiko; Tamura, Yutaka; Matsutani, Tomoo; Hirono, Seiichiro; Shinozaki, Natsuki; Hiwasa, Takaki; Takiguchi, Masaki; Saeki, Naokatsu

    2017-02-01

    Hypomethylation of genomic DNA induces stem-cell properties in cancer cells and contributes to the treatment resistance of various malignancies. To examine the correlation between the methylation status of stem-cell-related genes and the treatment outcomes in patients with glioblastoma (GBM). The genome-wide DNA methylation status was determined using HumanMethylation450 BeadChips, and the methylation status was compared between a group of patients with good prognosis (survival > 4 yr) and a group with poor prognosis (survival < 1 yr). Immunohistochemistry for proteins translated from hypomethylated genes, including alkaline phosphatase (ALPL), CD133, and CD44, was performed in 70 GBMs and 60 oligodendroglial tumors. The genomic DNA in refractory GBM was more hypomethylated than in GBM from patients with relatively long survival (P = .0111). Stem-cell-related genes including ALPL, CD133, and CD44 were also significantly hypomethylated. A validation study using immunohistochemistry showed that DNA hypomethylation was strongly correlated with high protein expression of ALPL, CD133, and CD44. GBM patients with short survival showed high expression of these stem-cell markers. Multivariate analysis confirmed that co-expression of ALPL + CD133 or ALPL + CD44 was a strong predictor of short survival. Anaplastic oligodendroglial tumors without isocitrate dehydrogenase 1 mutation were significantly correlated with high ALPL expression and poor survival. Accumulation of stem-cell properties due to aberrant DNA hypomethylation is associated with the refractory nature of GBM. Copyright © 2017 by the Congress of Neurological Surgeons

  1. Hypothermia for Neuroprotection in Convulsive Status Epilepticus.

    PubMed

    Legriel, Stephane; Lemiale, Virginie; Schenck, Maleka; Chelly, Jonathan; Laurent, Virginie; Daviaud, Fabrice; Srairi, Mohamed; Hamdi, Aicha; Geri, Guillaume; Rossignol, Thomas; Hilly-Ginoux, Julia; Boisramé-Helms, Julie; Louart, Benjamin; Malissin, Isabelle; Mongardon, Nicolas; Planquette, Benjamin; Thirion, Marina; Merceron, Sybille; Canet, Emmanuel; Pico, Fernando; Tran-Dinh, Yves-Roger; Bedos, Jean-Pierre; Azoulay, Elie; Resche-Rigon, Matthieu; Cariou, Alain

    2016-12-22

    Convulsive status epilepticus often results in permanent neurologic impairment. We evaluated the effect of induced hypothermia on neurologic outcomes in patients with convulsive status epilepticus. In a multicenter trial, we randomly assigned 270 critically ill patients with convulsive status epilepticus who were receiving mechanical ventilation to hypothermia (32 to 34°C for 24 hours) in addition to standard care or to standard care alone; 268 patients were included in the analysis. The primary outcome was a good functional outcome at 90 days, defined as a Glasgow Outcome Scale (GOS) score of 5 (range, 1 to 5, with 1 representing death and 5 representing no or minimal neurologic deficit). The main secondary outcomes were mortality at 90 days, progression to electroencephalographically (EEG) confirmed status epilepticus, refractory status epilepticus on day 1, "super-refractory" status epilepticus (resistant to general anesthesia), and functional sequelae on day 90. A GOS score of 5 occurred in 67 of 138 patients (49%) in the hypothermia group and in 56 of 130 (43%) in the control group (adjusted common odds ratio, 1.22; 95% confidence interval [CI], 0.75 to 1.99; P=0.43). The rate of progression to EEG-confirmed status epilepticus on the first day was lower in the hypothermia group than in the control group (11% vs. 22%; odds ratio, 0.40; 95% CI, 0.20 to 0.79; P=0.009), but there were no significant differences between groups in the other secondary outcomes. Adverse events were more frequent in the hypothermia group than in the control group. In this trial, induced hypothermia added to standard care was not associated with significantly better 90-day outcomes than standard care alone in patients with convulsive status epilepticus. (Funded by the French Ministry of Health; HYBERNATUS ClinicalTrials.gov number, NCT01359332 .).

  2. Chronic, refractory CRPS involving 3 limbs: a case report.

    PubMed

    Zyluk, A

    2013-06-01

    We report the case of a 26-year-old woman with CRPS involving consecutively 3 extremities during 8 years. None of the treatments used was effective and each CRPS episode resulted in persistence and chronification of the disease. We suggest that this patient presents a specific subtype of the disease, called "chronic, refractory CRPS" which is extremely severe, disabling and resistant to treatment. © Georg Thieme Verlag KG Stuttgart · New York.

  3. Selective T cell-depleted haploidentical hematopoietic stem cell transplantation for relapsed/refractory neuroblastoma.

    PubMed

    Liu, Anthony P Y; Lee, Pamela P W; Kwok, Janette S Y; Leung, Rock Y Y; Chiang, Alan K S; Ha, Shau-Yin; Cheuk, Daniel K L; Chan, Godfrey C F

    2018-06-19

    Relapsed/refractory NB carries a bleak outcome, warranting novel treatment options. HaploHSCT induces a graft-versus-NB effect via natural killer cell alloreactivity. Review of patients with relapsed/refractory NB who underwent haploHSCT with ex vivo T-cell depletion in our unit from 2013 through 2018. Ten patients were identified (male=5; median age at haploHSCT=6.45 y, range: 3.49-11.02 y). Indications were relapsed in 7 and refractoriness in 3; disease status at haploHSCT was CR in 2, PR in 6, and PD in 2. All patients received peripheral blood stem cell grafts after ex vivo T-cell depletion (CD3/CD19-depletion=1; TCR-αβ/CD19-depletion=4; CD3/CD45RA-depletion=4; and TCR-αβ/CD45RA-depletion=1). Conditioning regimens were fludarabine-based. Neutrophils engrafted on median D + 10 (range: D + 9 to +13), and platelets engrafted (≥20 × 10 9 /L) on median D + 8 (range: D + 5 to D + 14). Early T- and NK-cell recovery were evident. Of the 10 patients, acute rejection developed in 1 (who died of PD despite rescue HSCT), and 1 died of sepsis before engraftment; 8 experienced full donor-chimerism post-HSCT. Among the 8, 6 experienced CR, 1 died of PD, and 1 died of pulmonary hypertensive crisis before evaluation. At publication, 4 were in remission (2.8, 7.4, 28.5, and 58.9 months). No significant GvHD occurred. HaploHSCT with selective ex vivo T-cell depletion may be a safe and useful salvage strategy for relapsed/refractory NB. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. 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.

  5. Nutritional status deteriorates as the severity of diabetic foot ulcers increases and independently associates with prognosis.

    PubMed

    Zhang, Shan-Shan; Tang, Zheng-Yi; Fang, Ping; Qian, Hong-Jie; Xu, Lei; Ning, Guang

    2013-01-01

    The prognosis for diabetic foot ulcers (DFUs) remains poor. Nutritional status has not been identified as one of the factors affecting the outcome of DFUs. Therefore, indicators correlated with nutritional status and outcome were analyzed to investigate their relationship. A total of 192 hospitalized patients with Wagner grade 1-5 ulcers and 60 patients with Wagner grade 0 ulcers (all had type 2 diabetes) were assessed by the following: subjective global assessment (SGA), anthropometric measurements, biochemical indicators and physical examinations to evaluate nutritional status, severity of infection and complications. Patient outcome was recorded as healing of the ulcer and the patients were followed up for 6 months or until the wound was healed. The percentage of malnutrition was 62.0% in the DFU patients. The SGA was closely correlated with infection (r=0.64), outcome (r=0.37) and BMI (r=-0.36), all P<0.001. The risk of poor outcome increased with malnutrition [odds ratio (OR), 10.6, P<0.001]. The nutritional status of the DFU patients was independently correlated with the severity of infection and outcome (both P<0.001) and Wagner grades and nutritional status (SGA) were independent risk factors for patient outcome (both P<0.001). Nutritional status deteriorated as the severity of the DFU increased, and malnutrition was a predictor of poor prognosis.

  6. Non-CI refractory lithophile abundances in bulk planetary materials

    NASA Astrophysics Data System (ADS)

    Dauphas, N.

    2015-12-01

    Refractory inclusions in meteorites show evidence for fractionation of refractory lithophile elements relative to one another. For bulk planetary materials, it is most often assumed that refractory lithophile elements (e.g., Ca, Al, Ti, REEs) are in proportions similar to CI carbonaceous chondrites, which is taken to be a proxy for solar composition. A diagnostic feature of REE patterns in refractory inclusions in meteorites is the presence of thulium anomalies, arising from the fact that this heavy REE is more volatile than the highly refractory HREEs surrounding it (Tm/Tm* is defined relative to either Er-Yb or Er-Lu). Tm anomalies thus represent an excellent diagnostic tool to test the assumption that refractory lithophile elements have uniform relative abundances at a bulk planetary scale. Prior to this work, high precision Tm measurements were lacking because it is mono-isotopic and as such is not amenable to high-precision single spike measurements. We have developed a multi-collector REE abundance measurement technique to measure all REEs at high precision, including the mono-isotopic ones. This technique was used to revise the abundance of CI and PAAS REE abundances (Pourmand et al. 2012) and the CI composition agrees well with an independent study (Barrat et al. 2012). The same technique was applied to measure REE patterns in 41 chondrites as well as terrestrial rocks (Dauphas and Pourmand, 2015). Our results reveal the presence of Tm anomalies of about -4.5 % in terrestrial rocks, enstatite and ordinary chondrites, relative to carbonaceous chondrites including CIs. This demonstrates that the assumption that refractory lithophile elements are in constant proportions among planetary bodies is unwarranted. It also shows that carbonaceous chondrites cannot be a major constituent of the Earth. The presence of Tm anomalies in meteorites and terrestrial rocks suggests that either (i) the material in the inner part of the solar system was formed from a gas

  7. Changing physiological status predicts severe injury and need for specialized trauma center resources.

    PubMed

    Talbert, Steven

    2009-01-01

    This study evaluated the association between changing physiological status (delta data) with severe injury (SI) or need for trauma center resources (TCR). Prehospital and emergency department arrival weighted RTS (RTSw) were computed for patients with complete records entered into the registry from 2002 to 2004 (n = 23,753). Physiological change was classified as unchanged, deteriorated, or improved (PreRTSw vs EDRTSw). Performance of delta data was evaluated using standard epidemiological approaches and multiple logistic regression. Deterioration status predicted SI (operating room [OR] = 1.38) and TCR (OR = 2.09). Improved status predicted TCR (OR = 1.27). Delta data independently predicted both SI and TCR.

  8. Refractory ceramic fibers

    Integrated Risk Information System (IRIS)

    Refractory ceramic fibers ; CASRN Not found Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcino

  9. Impact of the severity of vasomotor symptoms on health status, resource use, and productivity.

    PubMed

    Whiteley, Jennifer; Wagner, Jan-Samuel; Bushmakin, Andrew; Kopenhafer, Lewis; Dibonaventura, Marco; Racketa, Jill

    2013-05-01

    The current study characterizes health-related quality of life, work productivity, and resource use among postmenopausal women by severity of vasomotor symptoms (VMS). Participants were selected from the 2010 US National Health and Wellness Survey. Women aged 40 to 75 years who did not report a history of menstrual bleeding or spotting for 1 year were eligible for analysis (N = 3,267). Cohorts of women with no VMS (n = 1,740), mild VMS (n = 931), moderate VMS (n = 462), and severe VMS (n = 134) were compared after controlling for demographic and health characteristics. Outcome measures were assessed using linear models and included health status, work productivity within the past 7 days, and healthcare resource use within the past 6 months. The mean age of women experiencing severe VMS was 57.92 years. After demographic and health characteristics had been controlled for, women experiencing severe and moderate VMS reported significantly lower mean health status scores compared with women with no symptoms (P < 0.0001). The mean number of menopause symptom-related physician visits was significantly greater among women with severe, moderate, or mild symptoms than among women with no symptoms (P < 0.0001). Among employed women experiencing VMS, women with severe and moderate symptoms had adjusted presenteeism of 24.28% and 14.3%, versus 4.33% in women with mild symptoms (P < 0.001), and activities of daily living impairment of 31.66% and 17.06%, versus 6.16% in women with mild symptoms (P < 0.0001). In postmenopausal women, a greater severity of VMS is significantly associated with lower levels of health status and work productivity, and greater healthcare resource use.

  10. Refractory thermowell for continuous high temperature measurement of molten metal

    DOEpatents

    Thiesen, Todd J.

    1992-01-01

    An apparatus for the continuous high temperature measurement of materials in vessels lined with rammed or cast refractory materials. A refractory housing member is integral with the refractory lining of the vessel and contains a plurality of high temperature sensing means, such as thermocouples. A face of the housing is flush with the refractory lining and contacts the high temperature material contained in the vessel. Continuous temperature measurement is achieved by a means which is coupled to the thermocouples for indicating the temperature.

  11. Pembrolizumab for Refractory Metastatic Myxofibrosarcoma: A Case Report.

    PubMed

    Song, Haa-Na; Kang, Min Gyu; Park, Jeong Rang; Hwang, Jin-Yong; Kang, Jung Hun; Lee, Won Seop; Lee, Gyeong-Won

    2018-01-22

    Myxofibrosarcoma is a rare tumor, refractory to cytotoxic chemotherapy and radiotherapy. Pembrolizumab is an innovative immunotherapy drug consisting of programmed death ligand receptor-1 (PD-L1) antibody proven to be useful for numerous types of cancer cells. A patient had been diagnosed with metastatic myxofibrosarcoma, refractory to radiotherapy and conventional cytotoxic chemotherapy. The patient achieved a partial response during palliative chemotherapy with pembrolizumab for 14 cycles. To the best of our knowledge, this is the first case report demonstrating the efficacy of pembrolizumab for refractory myxofibrosarcoma.

  12. Diagnosis and management of refractory celiac disease: a systematic review.

    PubMed

    Labidi, Asma; Serghini, Meriem; Karoui, Sami; Boubaker, Jalel; Filali, Azza

    2013-01-01

    Refractory celiac disease is defined by persisting malabsorptive symptoms in spite of a strict gluten free diet for at least 6 to 12 months. Alternatives to gluten free diet seem to be still controversial. To describe the clinical and epidemiologic aspects of refractory celiac disease, and to identify therapeutic options in this condition. Systematic review and critical analysis of observational studies, clinical trials and case reports that focused on diagnosis and management of refractory celiac disease. Refractory celiac disease can be classified as type 1 or type 2 according to the phenotype of intraepithelial lymphocytes. Great complications such as enteropathy-associated T-cell lymphoma may occur in a subgroup of these patients mainly in refractory celiac disease type 2. Curative therapies are still lacking. Refractory celiac disease remains a diagnosis of exclusion. Its prognosis remains still dismal by the absence yet of curative therapies. However, some new treatments seem to hold promise during few cohort-studies.

  13. 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.).

  14. Perioperative Care of a Patient with Refractory Idiopathic Thrombocytopenic Purpura Undergoing Total Knee Arthroplasty

    PubMed Central

    Gudimetla, Veera; Stewart, Andrew; Luscombe, Karen L; Charalambous, Charalambos P

    2012-01-01

    Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder leading to low platelet count and an increased risk of bleeding. Major joint replacement surgery in a patient with ITP can be associated with severe postoperative bleeding. We present our experience of perioperative management in a patient with severe refractory chronic idiopathic thrombocytopenic purpura who successfully underwent a cemented total knee replacement. PMID:23269964

  15. Non-pharmacological treatment options for refractory epilepsy: an overview of human treatment modalities and their potential utility in dogs.

    PubMed

    Martlé, Valentine; Van Ham, Luc; Raedt, Robrecht; Vonck, Kristl; Boon, Paul; Bhatti, Sofie

    2014-03-01

    Refractory epilepsy is a common disorder both in humans and dogs and treatment protocols are difficult to optimise. In humans, different non-pharmacological treatment modalities currently available include surgery, the ketogenic diet and neurostimulation. Surgery leads to freedom from seizures in 50-75% of patients, but requires strict patient selection. The ketogenic diet is indicated in severe childhood epilepsies, but efficacy is limited and long-term compliance can be problematic. In the past decade, various types of neurostimulation have emerged as promising treatment modalities for humans with refractory epilepsy. Currently, none of these treatment options are used in routine daily clinical practice to treat dogs with the condition. Since many dogs with poorly controlled seizures do not survive, the search for alternative treatment options for canine refractory epilepsy should be prioritised. This review provides an overview of non-pharmacological treatment options for human refractory epilepsy. The current knowledge and limitations of these treatments in canine refractory epilepsy is also discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Current Standard and Investigational Approaches to the Management of Hormone-Refractory Prostate Cancer

    PubMed Central

    Mendiratta, Prateek; Armstrong, Andrew J; George, Daniel J

    2007-01-01

    Prostate cancer is a common cause of death in men and remains incurable in the metastatic setting. In 2004, 2 landmark trials using docetaxel-based chemotherapy, TAX 327 and SWOG 99-16, showed a survival benefit for the first time in metastatic, hormone-refractory prostate cancer. Current research suggests that several distinct mechanisms of androgen-refractory disease may converge in patients with disease progression on androgen deprivation therapy. These findings have identified several potential targets for therapeutic intervention. Current standard and investigational treatment options for this disease are discussed, including chemotherapy and rapidly evolving therapies in phase II/III trials involving antiangiogenic therapies, signal transduction inhibitors, immunomodulatory agents, and nuclear receptor targets. In light of a growing array of treatment options and an increasingly chronic natural history, this review supports a multidisciplinary care approach to these patients, including medical oncologists, urologists, and radiation oncologists, to optimize survival and quality of life. PMID:17387372

  17. 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

  18. Ethnic Background, Socioeconomic Status, and Problem Severity as Dropout Risk Factors in Psychotherapy with Youth

    ERIC Educational Resources Information Center

    de Haan, Anna M.; Boon, Albert E.; Vermeiren, Robert R. J. M.; Hoeve, Machteld; de Jong, Joop T. V. M.

    2015-01-01

    Background: Dropout from child and adolescent psychotherapy is a common phenomenon which can have negative consequences for the individual later in life. It is therefore important to gain insight on dropout risk factors. Objective: Several potential risk factors [ethnic minority status, a lower socioeconomic status (SES), and higher problem…

  19. Refractoriness to immunochemotherapy in follicular lymphoma: Predictive factors and outcome.

    PubMed

    Sorigue, Marc; Mercadal, Santiago; Alonso, Sara; Fernández-Álvarez, Ruben; García, Olga; Moreno, Miriam; Pomares, Helena; Alcoceba, Miguel; González-García, Esther; Motlló, Cristina; González-Barca, Eva; Martin, Alejandro; Sureda, Anna; Caballero, Dolores; Ribera, Josep-María; Sancho, Juan-Manuel

    2017-12-01

    Follicular lymphoma is characterized by a good response to immunochemotherapy (ICT). However, a small percentage of patients responds poorly to treatment and seems to have a worse outcome. This study attempted to identify the predictive factors and outcome of refractoriness to first-line ICT. All patients diagnosed with stage II to IV follicular lymphoma between 2002 and 2014 and treated with first-line ICT in 4 Spanish institutions were analyzed. Those with no response or progression or relapse within 6 months of first-line response assessment were considered ICT refractory. Three hundred forty-three patients were included (median age 58 years, 48% male), of whom 53 (15%) were ICT refractory. On multivariate analysis, high-risk follicular lymphoma international prognostic index (FLIPI) score, B symptoms, and elevated β2-microglobulin were correlated with refractoriness, and refractoriness, high-risk FLIPI score, and β2-microglobulin were correlated with overall survival (OS). Compared with ICT-sensitive, ICT-refractory patients had a higher incidence of histological transformation (5-year cumulative incidence 25% [14%-39%] vs. 6% [3%-10%], P < .001), a higher rate of refractoriness to second-line therapy (16/33 [48%] vs. 13/57 [23%], P = .01), and a lower OS (5-year OS probability 38% [95% CI 23%-53%] vs. 87% [82%-92%%], P < .001). In conclusion, refractoriness to ICT was seen in 15% of patients and was predicted by high-FLIPI scores, B symptoms, and elevated serum β2-micrglobulin. Immunochemotherapy-refractory patients had a worse prognosis than ICT-sensitive patients, and current treatment options for this subgroup are not satisfactory. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Reaction Behaviors of Al-Killed Medium-Manganese Steel with Different Refractories

    NASA Astrophysics Data System (ADS)

    Kong, Lingzhong; Deng, Zhiyin; Zhu, Miaoyong

    2018-03-01

    In order to understand the reaction mechanism between medium-manganese steel and different refractories, some laboratory experiments were carried out at 1873 K (1600 °C). Three types of refractory plates (Al2O3, MgO, and MgO·Al2O3) were used. The results show that Mn in liquid medium-manganese steel does not react easily with the Al2O3 refractory, but can react with the MgO refractory to generate a (Mn, Mg)O layer at the boundary between the refractory plate and liquid steel. After the formation of (Mn, Mg)O, a layer of (Mn, Mg)O·Al2O3 spinel is also formed at the edge of the MgO refractory. Similar to the MgO refractory, the dissolved Mn can react with the MgO·Al2O3 refractory as well, and a layer of (Mn, Mg)O·Al2O3 was also detected after reaction. It was found that the formation of (Mn, Mg)O·Al2O3 at the edge of the refractory is a source of (Mn, Mg)O·Al2O3 inclusions in liquid steel. The flush-off of the (Mn, Mg)O·Al2O3 layer would result in the formation of (Mn, Mg)O·Al2O3 inclusions.

  1. Reaction Behaviors of Al-Killed Medium-Manganese Steel with Different Refractories

    NASA Astrophysics Data System (ADS)

    Kong, Lingzhong; Deng, Zhiyin; Zhu, Miaoyong

    2018-06-01

    In order to understand the reaction mechanism between medium-manganese steel and different refractories, some laboratory experiments were carried out at 1873 K (1600 °C). Three types of refractory plates (Al2O3, MgO, and MgO·Al2O3) were used. The results show that Mn in liquid medium-manganese steel does not react easily with the Al2O3 refractory, but can react with the MgO refractory to generate a (Mn, Mg)O layer at the boundary between the refractory plate and liquid steel. After the formation of (Mn, Mg)O, a layer of (Mn, Mg)O·Al2O3 spinel is also formed at the edge of the MgO refractory. Similar to the MgO refractory, the dissolved Mn can react with the MgO·Al2O3 refractory as well, and a layer of (Mn, Mg)O·Al2O3 was also detected after reaction. It was found that the formation of (Mn, Mg)O·Al2O3 at the edge of the refractory is a source of (Mn, Mg)O·Al2O3 inclusions in liquid steel. The flush-off of the (Mn, Mg)O·Al2O3 layer would result in the formation of (Mn, Mg)O·Al2O3 inclusions.

  2. Refractory materials in comet samples

    NASA Astrophysics Data System (ADS)

    Joswiak, D. J.; Brownlee, D. E.; Nguyen, A. N.; Messenger, S.

    2017-08-01

    Transmission electron microscope examination of more than 250 fragments, >1 μm from comet Wild 2 and a giant cluster interplanetary dust particle (GCP) of probable cometary origin has revealed four new calcium-aluminum-rich inclusions (CAIs), an amoeboid olivine aggregate (AOA), and an additional AOA or Al-rich chondrule (ARC) object. All of the CAIs have concentric mineral structures and are composed of spinel + anorthite cores surrounded by Al,Ti clinopyroxenes and are similar to two previous CAIs discovered in Wild 2. All of the cometary refractory objects are of moderate refractory character. The mineral assemblages, textures, and bulk compositions of the comet CAIs are similar to nodules in fine-grained, spinel-rich inclusions (FGIs) found in primitive chondrites and like the nodules may be nebular condensates that were altered via solid-gas reactions in the solar nebula. Oxygen isotopes collected on one Wild 2 CAI also match FGIs. The lack of the most refractory inclusions in the comet samples may reflect the higher abundances of small moderately refractory CAI nodules that were produced in the nebula and the small sample sizes collected. In the comet samples, approximately 2-3% of all fragments larger than 1 μm, by number, are CAIs and nearly 50% of all bulbous Stardust tracks contain at least one CAI. We estimate that 0.5 volume % of Wild 2 material and 1 volume % of GCP is in the form of CAIs. ARCs and AOAs account for <1% of the Wild 2 and GCP grains by number.

  3. Bumetanide is not capable of terminating status epilepticus but enhances phenobarbital efficacy in different rat models.

    PubMed

    Töllner, Kathrin; Brandt, Claudia; Erker, Thomas; Löscher, Wolfgang

    2015-01-05

    In about 20-40% of patients, status epilepticus (SE) is refractory to standard treatment with benzodiazepines, necessitating second- and third-line treatments that are not always successful, resulting in increased mortality. Rat models of refractory SE are instrumental in studying the changes underlying refractoriness and to develop more effective treatments for this severe medical emergency. Failure of GABAergic inhibition is a likely cause of the development of benzodiazepine resistance during SE. In addition to changes in GABAA receptor expression, trafficking, and function, alterations in Cl(-) homeostasis with increased intraneuronal Cl(-) levels may be involved. Bumetanide, which reduces intraneuronal Cl(-) by inhibiting the Cl(-) intruding Na(+), K(+), Cl(-) cotransporter NKCC1, has been reported to interrupt SE induced by kainate in urethane-anesthetized rats, indicating that this diuretic drug may be an interesting candidate for treatment of refractory SE. In this study, we evaluated the effects of bumetanide in the kainate and lithium-pilocarpine models of SE as well as a model in which SE is induced by sustained electrical stimulation of the basolateral amygdala. Unexpectedly, bumetanide alone was ineffective to terminate SE in both conscious and anesthetized adult rats. However, it potentiated the anticonvulsant effect of low doses of phenobarbital, although this was only seen in part of the animals; higher doses of phenobarbital, particularly in combination with diazepam, were more effective to terminate SE than bumetanide/phenobarbital combinations. These data do not suggest that bumetanide, alone or in combination with phenobarbital, is a valuable option in the treatment of refractory SE in adult patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Assessment of nutritional status in patients with Parkinson's disease and its relationship with severity of the disease.

    PubMed

    Shidfar, Farzad; Babaii Darabkhani, Peivand; Yazdanpanah, Leila; Karkheiran, Siamak; Noorollahi-Moghaddam, Hamid; Haghani, Hamid

    2016-01-01

    Background: Malnutrition, loss of body weight, muscle and fat mass wasting are common in patients with Parkinson's disease, and are associated with disability, longer length of hospital stay, impaired immune system and increased risk of mortality. The aim of this study was to assess the nutritional status in patients with Parkinson's disease and its relation to the severity of the disease. Methods: This cross- sectional study was conducted on 130 patients with Parkinson's disease, with a mean (SD) age of 59.1 (12.9) years in disease stages of 1 to 4. In this study, the Mini Nutritional Assessment (MNA) questionnaire was used along with anthropometric measurements (Body Mass Index (BMI), Mid-arm circumference (MAC), Calf Circumference (CC)) to evaluate the nutritional status, and they were applied by a trained nutritionist. Hoehn and Yahr Scale were used to determine the severity of the disease. One-way ANOVA test was used to assess the relationship between anthropometric indices, nutritional status and severity of disease. Assessment of the relationship between age, duration of disease and nutritional status was categorized according to MNA score, and was performed, using one-way ANOVA. Chi - Square test was utilized to assess the relationship between education level and nutritional status. SPSS Version 18 was used for data analysis. Results: In this study, 30% (n=39) of the participants were diagnosed with normal nutritional status, 58.5% (n=76) were at risk of malnutrition and 11.5% (n=15) were malnourished according to MNA. Reduction of weight, and muscle mass wasting was observed in different disease stages. Muscle mass wasting and worsening nutritional status, based on MNA score, showed a significant increase as the disease progressed, MAC (p=0.009), MNA score (p<0.001). After assessing the relationship between education level, age, duration of disease with nutritional status, the results revealed a significant relationship between age (p=0.008), education

  5. The effects of adjunctive topiramate therapy on seizure severity and health-related quality of life in patients with refractory epilepsy---a Canadian study.

    PubMed

    Baker, Gus A; Currie, Natalie G T; Light, Margaret J; Schneiderman, Jack H

    2002-01-01

    Although reduction in seizure frequency is the most common endpoint used to assess the antiepileptic efficacy, seizure frequency alone does not provide a complete picture of effectiveness, particularly in patients with refractory epilepsy. The aim of our study was to assess the effects of topiramate on seizure severity and health-related quality of life (HRQL), in addition to standard efficacy measures, in an open, multicentre, 6-month trial of patients with epilepsy uncontrolled on antiepileptic drugs other than topiramate. Two hundred and nine patients were enrolled and received topiramate for up to 6 months (initiated at 50 mg/day and titrated to a recommended dose of 200-400 mg/day) in addition to existing medication. The median reduction in seizure frequency from baseline to the post-titration period was 40.9% ( P< 0.0001). Patients also demonstrated a mean reduction in the Liverpool Seizure Severity Scale (LSSS) of 5.3 ( P< 0.0001), which was considered clinically significant. Statistically significant changes in HRQL were not observed with the SF-36, a generic measure. Tolerability of antiepileptic medication was good, with a low incidence of cognitive adverse events. The results indicate that topiramate significantly reduces seizure severity---an important aspect of HRQL---when administered as adjunctive therapy to anticonvulsant therapy. Copyright 2002 BEA Trading Ltd.

  6. 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.

  7. Refractory rheumatoid vasculitis

    PubMed Central

    Kumar, Ashok; Goel, Anshul; Lapsiwala, Mehul; Singhal, Suman

    2016-01-01

    Systemic rheumatoid vasculitis (SRV) can develop in rheumatoid arthritis of long duration and high disease activity. It most commonly manifests as cutaneous vasculitis and mononeuritis multiplex. This can involve any organ of the body and carries very high mortality. We report a case of a young male who had rheumatoid arthritis for the past 15 years and became refractory to standard drugs and anti-TNF agents. He subsequently developed SRV, which started as mononeuritis multiplex. Disease progressed to result in gangrene of hands and feet despite receiving intravenous cyclophosphamide. Intravenous immunoglobulin and rituximab also could not provide any response. Prolonged ICU stay resulted in critical care neuromyopathy. Central nervous system vasculitis developed even after repeated infusions of intravenous immunoglobulins and at last he died of complications. In this case report, we have presented rare and chronic protracted presentation of rheumatoid vasculitis involving skin, nerves, brain and testis, which was refractory to the recommended therapies. PMID:28031844

  8. Forming Refractory Insulation On Copper Wire

    NASA Technical Reports Server (NTRS)

    Setlock, J.; Roberts, G.

    1995-01-01

    Alternative insulating process forms flexible coat of uncured refractory insulating material on copper wire. Coated wire formed into coil or other complex shape. Wire-coating apparatus forms "green" coat on copper wire. After wire coiled, heating converts "green" coat to refractory electrical insulator. When cured to final brittle form, insulating material withstands temperatures above melting temperature of wire. Process used to make coils for motors, solenoids, and other electrical devices to be operated at high temperatures.

  9. Tocilizumab for the treatment of severe steroid-refractory acute graft-versus-host disease of the lower gastrointestinal tract.

    PubMed

    Ganetsky, Alex; Frey, Noelle V; Hexner, Elizabeth O; Loren, Alison W; Gill, Saar I; Luger, Selina M; Mangan, James K; Martin, Mary Ellen; Babushok, Daria V; Drobyski, William R; Smith, Jacqueline; Timlin, Colleen; Freyer, Craig W; Stadtmauer, Edward A; Porter, David L

    2018-05-24

    Steroid-refractory (SR) acute gastrointestinal (GI) graft-versus-host disease (GVHD) is associated with significant mortality in allogeneic hematopoietic cell transplantation recipients. We retrospectively evaluated the efficacy of tocilizumab for the treatment of SR biopsy-proven acute lower GI GVHD in 16 consecutive adult transplant recipients between October 2015 and July 2016. Tocilizumab 8 mg/kg was administered every 2 weeks until achievement of complete response, defined as resolution of all manifestations of GI GVHD, or until patients had progression or initiation of other therapy. Ten of 16 patients (62.5%; 95% CI, 0.39-82) achieved a complete response after a median time of 11 days (range, 2-28 days) from tocilizumab initiation. The median time to response onset (improvement in stage by at least 1) was 1 day (range, 1-4 days). Tocilizumab was administered at a median of 9 days (range, 3-75 days) from GVHD diagnosis and 10 days (range, 3-75 days) from initiation of high-dose steroids. At a median follow-up of 7.6 months (range, 0.8-27.7 months) from initiation of tocilizumab, 6/16 (37.5%) patients are alive and free of their underlying hematologic malignancy. Tocilizumab appears to be a highly active agent for the treatment of severe SR lower GI acute GVHD.

  10. Risk of recurrent or refractory strictures and outcome of endoscopic dilation for radiation-induced esophageal strictures.

    PubMed

    Agarwalla, Anant; Small, Aaron J; Mendelson, Aaron H; Scott, Frank I; Kochman, Michael L

    2015-07-01

    Radiation therapy for head, neck, and esophageal cancer can result in esophageal strictures that may be difficult to manage. Radiation-induced esophageal strictures often require repeat dilation to obtain relief of dysphagia. This study aimed to determine the long-term clinical success and rates of recurrent and refractory stenosis in patients with radiation-induced strictures undergoing dilation. Retrospective cohort study of patients with radiation-induced strictures who underwent endoscopic dilation by a single provider from October 2007-October 2012. Outcomes measured included long-term clinical efficacy, interval between sessions, number of dilations, and proportion of radiation strictures that were recurrent or refractory. Risk factors for refractory strictures were assessed. 63 patients underwent 303 dilations. All presented with a stricture >30 days after last radiation session. Clinical success to target diameter was achieved in 52 patients (83%). A mean of 3.3 (±2.6) dilations over a median period of 4 weeks was needed to achieve initial patency. Recurrence occurred in 17 (33%) at a median of 22 weeks. Twenty-seven strictures (43%) were refractory to dilation therapy. Fluoroscopy during dilation (OR 22.88; 95% CI 3.19-164.07), severe esophageal stenosis (lumen <9 mm) (OR 10.51; 95% CI 1.94-56.88), and proximal location with prior malignancy extrinsic to the lumen (OR 6.96; 95% CI 1.33-36.29) were independent predictors of refractory strictures in multivariate analysis. (1) Radiation-induced strictures have a delayed onset (>30 days) from time of radiation injury. (2) Endoscopic dilation can achieve medium-term luminal remediation but the strictures have a high long-term recurrence rate of up to 33%. (3) Remediation of radiation strictures following laryngectomy can be achieved but require frequent dilations. (4) Clinical and procedural predictors may identify patients at high risk of refractory strictures. (5) The optimal strategy in highly selected

  11. Reprint of: Relationship between cataract severity and socioeconomic status.

    PubMed

    Wesolosky, Jason D; Rudnisky, Christopher J

    2015-06-01

    To determine the relationship between cataract severity and socioeconomic status (SES). Retrospective, observational case series. A total of 1350 eyes underwent phacoemulsification cataract extraction by a single surgeon using an Alcon Infiniti system. Cataract severity was measured using phaco time in seconds. SES was measured using area-level aggregate census data: median income, education, proportion of common-law couples, and employment rate. Preoperative best corrected visual acuity was obtained and converted to logarithm of the minimum angle of resolution values. For patients undergoing bilateral surgery, the generalized estimating equation was used to account for the correlation between eyes. Univariate analyses were performed using simple regression, and multivariate analyses were performed to account for variables with significant relationships (p < 0.05) on univariate testing. Sensitivity analyses were performed to assess the effect of including patient age in the controlled analyses. Multivariate analyses demonstrated that cataracts were more severe when the median income was lower (p = 0.001) and the proportion of common-law couples living in a patient's community (p = 0.012) and the unemployment rate (p = 0.002) were higher. These associations persisted even when controlling for patient age. Patients of lower SES have more severe cataracts. Copyright © 2015. Published by Elsevier Inc.

  12. 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.

  13. Challenges in the treatment of convulsive status epilepticus.

    PubMed

    Zaccara, Gaetano; Giannasi, Gianfranco; Oggioni, Roberto; Rosati, Eleonora; Tramacere, Luciana; Palumbo, Pasquale

    2017-04-01

    Convulsive status epilepticus (CSE) is a medical emergency associated with high mortality and morbidity. The most recent definition of CSE is a convulsive seizure lasting more than 5min or consecutive seizures without recovery of consciousness. In adults, for the treatment of the early stages of CSE, diazepam, lorazepam or midazolam are the most common treatments, although the choice of agent seems less important than rapid treatment. Midazolam, when administered intramuscularly (best evidence), buccally, or nasally, is effective and safe in the pre-hospital setting. The antiepileptic drugs, phenytoin, valproate, levetiracetam and, more recently lacosamide, are used in CSE that persists after first-line treatments (established CSE). Phenytoin is more difficult to administer and is less well tolerated. Evidence of the efficacy of lacosamide is scarce. Anaesthetics are the drugs of choice for the treatment of refractory CSE (not responding to second-line drugs). Midazolam seems to be the best tolerated and is the most often used drug, followed by propofol and thiopental (pentobarbital in the USA). A few studies indicate that ketamine is effective with the possible advantage that it can be co-administered with other anaesthetics, such as midazolam or propofol. CSE becomes super-refractory after more than 24h of appropriate treatments and may last weeks. Several anaesthetics have been proposed but evidence is scarce. Autoimmune refractory CSE has been recently identified, and early treatment with immuno-modulatory agents (corticosteroids and IV immunoglobulins and also second-line agents such as cyclophosphamide and rituximab followed by chronic immunosuppressive treatment) is now recommended by many experts. Copyright © 2017. Published by Elsevier Ltd.

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

    PubMed

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

    2016-01-01

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

  15. 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.

  16. Allogeneic transplantation using CD34+ selected peripheral blood progenitor cells combined with non-mobilized donor T cells for refractory severe aplastic anaemia.

    PubMed

    Purev, Enkhtsetseg; Tian, Xin; Aue, Georg; Pantin, Jeremy; Vo, Phuong; Shalabi, Reem; Reger, Robert N; Cook, Lisa; Ramos, Catalina; Cho, Elena; Worthy, Tat'yana; Khuu, Hanh; Stroncek, David; Young, Neal S; Childs, Richard W

    2017-03-01

    Allogeneic haematopoietic stem cell transplantation is curative for severe aplastic anaemia (SAA) unresponsive to immunosuppressive therapy. To reduce chronic graft-versus-host disease (GVHD), which occurs more frequently after peripheral blood stem cell (PBSC) transplantation compared to bone-marrow transplantation (BMT), and to prevent graft rejection, we developed a novel partial T-cell depleted transplant that infuses high numbers of granulocyte colony-stimulating factor-mobilized CD34 + selected PBSCs combined with a BMT-equivalent dose of non-mobilized donor T-cells. Fifteen patients with refractory SAA received cyclophosphamide, anti-thymocyte globulin and fludarabine conditioning, and were transplanted with a median 8 × 10 6 CD34 +  cells/kg and 2 × 10 7 non-mobilized CD3 + T-cells/kg from human leucocyte antigen-matched sibling donors. All achieved sustained engraftment with only two developing acute and two developing chronic GVHD. With a 3·5-year median follow-up, 86% of patients survived and were transfusion-independent. When compared to a retrospective cohort of 56 bone-marrow failure patients that received the identical transplant preparative regimen and GVHD prophylaxis with the exception that the allograft contained unmanipulated PBSCs, partial T-cell depleted transplant recipients had delayed donor T-cell chimerism and relative reduction of 75% in the incidence of acute grade II-IV GVHD (13% vs. 52%; P = 0·010) and of 82% in chronic GVHD (13% vs. 72%; P = 0·0004). In multivariate analysis, partial T-cell depleted transplants remained significantly associated with a reduced risk of GVHD. In conclusion, for patients with refractory SAA, this novel transplant strategy achieves excellent engraftment and survival when compared to unmanipulated PBSC transplants and dramatically reduces the incidence of both acute and chronic GVHD. © 2017 John Wiley & Sons Ltd.

  17. Status epilepticus severity score (STESS): A useful tool to predict outcome of status epilepticus.

    PubMed

    Goyal, Manoj Kumar; Chakravarthi, Sudheer; Modi, Manish; Bhalla, Ashish; Lal, Vivek

    2015-12-01

    The treatment protocols for status epilepticus (SE) range from small doses of intravenous benzodiazepines to induction of coma. The pros and cons of more aggressive treatment regimen remain debatable. The importance of an index need not be overemphasized which can predict outcome of SE and guide the intensity of treatment. We tried to evaluate utility of one such index Status epilepticus severity score (STESS). 44 consecutive patients of SE were enrolled in the study. STESS results were compared with various outcome measures: (a) mortality, (b) final neurological outcome at discharge as defined by functional independence measure (FIM) (good outcome: FIM score 5-7; bad outcome: FIM score 1-4), (c) control of SE within 1h of start of treatment and (d) need for coma induction. A higher STESS score correlated significantly with poor neurological outcome at discharge (p=0.0001), need for coma induction (p=0.0001) and lack of response to treatment within 1h (p=0.001). A STESS of <3 was found to have a negative predictive value of 96.9% for mortality, 96.7% for poor neurological outcome at discharge and 96.7% for need of coma induction, while a STESS of <2 had negative predictive value of 100% for mortality, coma induction and poor neurological outcome at discharge. STESS can reliably predict the outcome of status epilepticus. Further studies on STESS based treatment approach may help in designing better therapeutic regimens for SE. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. [Marital status and the severity of perinatal depression among pregnant women].

    PubMed

    Podolska, Magdalena; Sipak-Szmigiel, Olimpia

    2010-01-01

    Cohabitation existing for ages in all human cultures is becoming more common since the 1960s due to complex changes in postmodern societies. These societies have made the phenomenon of cohabitation the object of adequate theoretical reflection. The aim of this work was to determine whether the marital status of pregnant women affects the severity of perinatal depression. We enrolled 117 gravida hospitalized in 2006 and 2007 at the Department of Maternal-Fetal Medicine, Pomeranian Medical University. The gestational age ranged from week 32 to 40. The clinical condition of each gravida was assessed during routine obstetric history taking. The Edinburgh Postnatal Depression Scale by Cox, Holden, and Sagovski was used as the screening test for perinatal depression. 1. The marital status of the gravida with emphasis on cohabitation is a significant correlate of perinatal depression and its risk. 2. Clinical examination should concentrate not only on the physical and medical condition but also on the psychosocial status of the patient as the predictor of perinatal depression. 3. All pregnant women living in informal partnerships should be offered psychological support.

  19. Treatment of status migrainosus by general anesthesia: a case report.

    PubMed

    Udelsmann, Artur; Saccomani, Priscila; Dreyer, Elisabeth; da Costa, Alberto Luiz Cunha

    2015-01-01

    The status migrainosus is a complication of migraine characterized by severe headache for more than 72h that did not respond to treatment, with risk of stroke and suicide. Researches on treatment are directed to drugs that stimulate GABA receptors; propofol and isoflurane act on sub-GABAa receptors and theoretically could be interesting. The first has been the subject of research in severe migraine. Opioids are employed in pain, and its use in chronic headache is debatable, but these agents are employed in acute cases. The goal is to present a case of refractory status migrainosus in that we decided to break the pain cycle by general anesthesia. Female patient, aged 50 years, with status migrainosus, in the last five days with visits to the emergency department, medicated parenterally with various agents without result. Without comorbidities, dehydrated, described her pain as "well over 10" in Visual Numeric Scale (VNS). After consulting the literature, and given the apparent severity of the condition, we opted for a general anesthesia: induction with fentanyl, propofol, and vecuronium and maintenance with isoflurane and propofol for two hours. Following the treatment, in the postanesthetic recuperation (PAR), the patient related her pain as VNS 3, and was released after five hours with VNS 2. Subsequently, her preventive treatment was resumed. Status migrainosus is a rare disabling complication and anesthetics have been the subject of research in its treatment; the option for general anesthesia with agents that stimulate GABA receptors, propofol and isoflurane, in association with fentanyl, proved effective and should encourage new research. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  20. [Treatment of status migrainosus by general anesthesia: a case report].

    PubMed

    Udelsmann, Artur; Saccomani, Priscila; Dreyer, Elisabeth; Costa, Alberto Luiz Cunha da

    2015-01-01

    The status migrainosus is a complication of migraine characterizedby severe headache for more than 72 h that did not respond to treatment, with risk of strokeand suicide. Researches on treatment are directed to drugs that stimulate GABA receptors; propofol and isoflurane act on sub-GABAa receptors and theoretically could be interesting. The first has been the subject of research in severe migraine. Opioids are employed in pain, and its use in chronic headache is debatable, but these agents are employed in acute cases. The goalis to present a case of refractory status migrainosus in that we decided to break the pain cycle by general anesthesia. Female patient, aged 50 years, with status migrainosus, in the last five days withvisits to the emergency department, medicated parenterally with various agents without result. Without comorbidities, dehydrated, described her pain as "well over 10" in Visual NumericScale (VNS). After consulting the literature, and given the apparent severity of the condition, we opted for a general anesthesia: induction with fentanyl, propofol, and vecuroniumand maintenance with isoflurane and propofol for two hours. Following the treatment, in the postanesthetic recuperation (PAR), the patient related her pain as VNS 3, and was released after five hours with VNS 2. Subsequently, her preventive treatment was resumed. Status migrainosus is a rare disabling complication and anesthetics have been the subject of research in its treatment; the option for general anesthesia with agents that stimulate GABA receptors, propofol and isoflurane, in association with fentanyl, proved effective and should encourage new research. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  1. Refractory Oxide Coatings on Sic Ceramics

    NASA Technical Reports Server (NTRS)

    Lee, Kang N.; Jacobson, Nathan S.; Miller, Robert A.

    1994-01-01

    Silicon carbide with a refractory oxide coating is potentially a very attractive ceramic system. It offers the desirable mechanical and physical properties of SiC and the environmental durability of a refractory oxide. The development of a thermal shock resistant plasma-sprayed mullite coating on SiC is discussed. The durability of the mullite/SiC in oxidizing, reducing, and molten salt environments is discussed. In general, this system exhibits better behavior than uncoated SiC. Areas for further developments are discussed.

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

    PubMed

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

    2011-03-29

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

  3. 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.

  4. Anesthetic drugs in status epilepticus: Risk or rescue?

    PubMed Central

    Marsch, Stephan; Fuhr, Peter; Kaplan, Peter W.; Rüegg, Stephan

    2014-01-01

    Objective: To evaluate the risks of continuously administered IV anesthetic drugs (IVADs) on the outcome of adult patients with status epilepticus (SE). Methods: All intensive care unit patients with SE from 2005 to 2011 at a tertiary academic medical care center were included. Relative risks were calculated for the primary outcome measures of seizure control, Glasgow Outcome Scale score at discharge, and death. Poisson regression models were used to control for possible confounders and to assess effect modification. Results: Of 171 patients, 37% were treated with IVADs. Mortality was 18%. Patients with anesthetic drugs had more infections during SE (43% vs 11%; p < 0.0001) and a 2.9-fold relative risk for death (2.88; 95% confidence interval 1.45–5.73), independent of possible confounders (i.e., duration and severity of SE, nonanesthetic third-line antiepileptic drugs, and critical medical conditions) and without significant effect modification by different grades of SE severity and etiologies. As IVADs were used after first- and second-line drugs failed, there was a correlation between treatment-refractory SE and the use of IVADs, leading to insignificant results regarding the risk of IVADs and outcome after additional adjustment for refractory SE. Conclusion: Our findings heighten awareness regarding adverse effects of IVADs. Randomized controlled trials are needed to further clarify the association of IVADs with outcome in patients with SE. Classification of evidence: This study provides Class III evidence that patients with SE receiving IVADs have a higher proportion of infection and an increased risk of death as compared to patients not receiving IVADs. PMID:24319039

  5. Refractory Status Epilepticus in Children: intention-to-treat with continuous infusions of midazolam and pentobarbital

    PubMed Central

    Tasker, Robert C; Goodkin, Howard P; Fernández, Iván Sánchez; Chapman, Kevin E; Abend, Nicholas S; Arya, Ravindra; Brenton, James N; Carpenter, Jessica L; Gaillard, William D; Glauser, Tracy A; Goldstein, Joshua; Helseth, Ashley R; Jackson, Michele C; Kapur, Kush; Mikati, Mohamad A; Peariso, Katrina; Wainwright, Mark S; Wilfong, Angus A; Williams, Korwyn; Loddenkemper, Tobias

    2016-01-01

    Objective To describe pediatric patients with convulsive refractory status epilepticus (RSE) in whom there is intention-to-use an intravenous anesthetic for seizure control. Design Two-year prospective observational study evaluating patients (age range one month to 21 years) with RSE not responding to two antiepileptic drug classes and treated with continuous infusion of anesthetic agent. Setting Nine pediatric hospitals in the United States. Patients In a cohort of 111 patients with RSE (median age 3.7 years, 50% male), 54 (49%) underwent continuous infusion of anesthetic treatment. Main Results The median (interquartile range, IQR) intensive care unit length-of-stay was 10 (3–20) days. Up to four ‘cycles’ of serial anesthetic therapy were used and seizure termination was achieved in 94% by the second cycle. Seizure duration in controlled patients was 5.9 (1.9–34) hours for the first cycle, and longer when a second cycle was required (30 [4,−120] hours, p=0.048). Midazolam was the most frequent first-line anesthetic agent (78%); pentobarbital was the most frequently used second-line agent after midazolam failure (82%). An electroencephalographic endpoint was used in over half of the patients; higher midazolam dosing was used with a burst suppression endpoint. In midazolam non-responders, transition to a second agent occurred after a median of one day. Most patients (94%) experienced seizure termination with these two therapies. Conclusions Midazolam and pentobarbital remains the mainstay of continuous infusion therapy for RSE in the pediatric patient. The majority of patients experience seizure termination within a median of 30 hours. These data have implications for the design and feasibility of future intervention trials. That is, testing a new anesthetic anticonvulsant after failure of both midazolam and pentobarbital is unlikely to be feasible in a pediatric study, whereas a decision to test an alternative to pentobarbital, after midazolam failure

  6. P2X receptors as targets for the treatment of status epilepticus

    PubMed Central

    Henshall, David C.; Diaz-Hernandez, Miguel; Miras-Portugal, M. Teresa; Engel, Tobias

    2013-01-01

    Prolonged seizures are amongst the most common neurological emergencies. Status epilepticus is a state of continuous seizures that is life-threatening and prompt termination of status epilepticus is critical to protect the brain from permanent damage. Frontline treatment comprises parenteral administration of anticonvulsants such as lorazepam that facilitate γ-amino butyric acid (GABA) transmission. Because status epilepticus can become refractory to anticonvulsants in a significant proportion of patients, drugs which act on different neurotransmitter systems may represent potential adjunctive treatments. P2X receptors are a class of ligand-gated ion channel activated by ATP that contributes to neuro- and glio-transmission. P2X receptors are expressed by both neurons and glia in various brain regions, including the hippocampus. Electrophysiology, pharmacology and genetic studies suggest certain P2X receptors are activated during pathologic brain activity. Expression of several members of the family including P2X2, P2X4, and P2X7 receptors has been reported to be altered in the hippocampus following status epilepticus. Recent studies have shown that ligands of the P2X7 receptor can have potent effects on seizure severity during status epilepticus and mice lacking this receptor display altered seizures in response to chemoconvulsants. Antagonists of the P2X7 receptor also modulate neuronal death, microglial responses and neuroinflammatory signaling. Recent work also found altered neuronal injury and inflammation after status epilepticus in mice lacking the P2X4 receptor. In summary, members of the P2X receptor family may serve important roles in the pathophysiology of status epilepticus and represent novel targets for seizure control and neuroprotection. PMID:24324404

  7. P2X receptors as targets for the treatment of status epilepticus.

    PubMed

    Henshall, David C; Diaz-Hernandez, Miguel; Miras-Portugal, M Teresa; Engel, Tobias

    2013-11-26

    Prolonged seizures are amongst the most common neurological emergencies. Status epilepticus is a state of continuous seizures that is life-threatening and prompt termination of status epilepticus is critical to protect the brain from permanent damage. Frontline treatment comprises parenteral administration of anticonvulsants such as lorazepam that facilitate γ-amino butyric acid (GABA) transmission. Because status epilepticus can become refractory to anticonvulsants in a significant proportion of patients, drugs which act on different neurotransmitter systems may represent potential adjunctive treatments. P2X receptors are a class of ligand-gated ion channel activated by ATP that contributes to neuro- and glio-transmission. P2X receptors are expressed by both neurons and glia in various brain regions, including the hippocampus. Electrophysiology, pharmacology and genetic studies suggest certain P2X receptors are activated during pathologic brain activity. Expression of several members of the family including P2X2, P2X4, and P2X7 receptors has been reported to be altered in the hippocampus following status epilepticus. Recent studies have shown that ligands of the P2X7 receptor can have potent effects on seizure severity during status epilepticus and mice lacking this receptor display altered seizures in response to chemoconvulsants. Antagonists of the P2X7 receptor also modulate neuronal death, microglial responses and neuroinflammatory signaling. Recent work also found altered neuronal injury and inflammation after status epilepticus in mice lacking the P2X4 receptor. In summary, members of the P2X receptor family may serve important roles in the pathophysiology of status epilepticus and represent novel targets for seizure control and neuroprotection.

  8. 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

  9. 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.

  10. Short-Term Effects of Pulsed Radiofrequency on Chronic Refractory Cervical Radicular Pain

    PubMed Central

    Choi, Gyu-Sik; Cho, Yun-Woo; Lee, Dong-Kyu

    2011-01-01

    Objective To evaluate the short-term effectiveness of pulsed radiofrequency on the dorsal root ganglion (DRG) in patients with chronic refractory cervical radicular pain. Method Fifteen patients (13 males, 2 females; mean age, 55.9 years) with chronic radicular pain due to cervical disc herniation or foraminal stenosis refractory to active rehabilitative management, including transforaminal cervical epidural steroid injection and exercise, were selected. All patients received pulsed radiofrequency on the symptomatic cervical dorsal root ganglion and were carefully evaluated for neurologic deficits and side effects. The clinical outcomes were measured using a visual analogue scale (VAS) and a neck disability index (NDI) before treatment, one and three months after treatment. Successful pain relief was defined as a 50% or greater reduction in the VAS score as compared with the pre-treatment score. After three months, we categorized the patients' satisfaction. Results The average VAS for radicular pain was reduced significantly from 5.3 at pretreatment to 2.5 at 3 months post-treatment (p<0.05). Eleven of 15 patients (77.3%) after cervical pulsed RF stimulation reported pain relief of 50% or more at the 3 month follow-up. The average NDI was significantly reduced from 44.0% at pretreatment to 35.8% 3 months post-treatment (p<0.05). At 3 months post-treatment, eleven of fifteen patients (73.3%) were satisfied with their status. No adverse effects were observed. Conclusion The results demonstrate that the application of pulsed radiofrequency on DRG might be an effective short-term intervention for chronic refractory cervical radicular pain. Further studies, including a randomized controlled trial with long-term follow-up, are now needed. PMID:22506211

  11. The Use Of Phosphates To Reduce Slag Penetration In Cr203-Based Refractories

    DOEpatents

    Kwong, Kyei-Sing; Dogan, Cynthia P.; Bennett, James P.; Chinn, Richard E.; Petty, Arthur V.

    2004-11-09

    A high-chromium refractory material that provides improved resistance to coal slag penetration is presented. The refractory mixture comprises a blend of chromium oxide, aluminum oxide and phosphates. The refractory mixture may be blended with an aggregate and cured. In addition a phosphorous oxide may be blended with chromium oxide and aluminum oxide and additionally an aggregate. The refractory mixture reduces the rate of coal slag penetration into the surface of the cured refractory.

  12. Use of Serum Infliximab Level Prior to Cyclosporine Salvage Therapy in Severe Ulcerative Colitis

    PubMed Central

    Bochenek, Ashley; Stein, Adam C.; Rubin, David T.

    2014-01-01

    Medical treatment options for severe, steroid refractory ulcerative colitis (UC) include infliximab (IFX) or cyclosporine (CSA), but general consensus has been that both agents should not be used together or even successively. We report a case of a 17-year-old male with severe UC refractory to IV steroids with successful sequential salvage therapy guided by serum IFX level. After primary lack of response to IFX, an undetectable serum IFX level and elevated IFX antibodies were followed by immediate transition to IV CSA. This case demonstrates the possibility of therapeutic drug monitoring of IFX levels when calculating the risk/benefit ratio for patients with steroid-refractory UC failing primary salvage therapy. PMID:26157857

  13. Composition and process for making an insulating refractory material

    DOEpatents

    Pearson, A.; Swansiger, T.G.

    1998-04-28

    A composition and process are disclosed for making an insulating refractory material. The composition includes calcined alumina powder, flash activated alumina powder, an organic polymeric binder and a liquid vehicle which is preferably water. Starch or modified starch may also be added. A preferred insulating refractory material made with the composition has a density of about 2.4--2.6 g/cm{sup 3} with reduced thermal conductivity, compared with tabular alumina. Of importance, the formulation has good abrasion resistance and crush strength during intermediate processing (commercial sintering) to attain full strength and refractoriness.

  14. Dependency of Calcium Alternans on Ryanodine Receptor Refractoriness

    PubMed Central

    Alvarez-Lacalle, Enric; Cantalapiedra, Inma R.; Peñaranda, Angelina; Cinca, Juan; Hove-Madsen, Leif; Echebarria, Blas

    2013-01-01

    Background Rapid pacing rates induce alternations in the cytosolic calcium concentration caused by fluctuations in calcium released from the sarcoplasmic reticulum (SR). However, the relationship between calcium alternans and refractoriness of the SR calcium release channel (RyR2) remains elusive. Methodology/Principal Findings To investigate how ryanodine receptor (RyR2) refractoriness modulates calcium handling on a beat-to-beat basis using a numerical rabbit cardiomyocyte model. We used a mathematical rabbit cardiomyocyte model to study the beat-to-beat calcium response as a function of RyR2 activation and inactivation. Bi-dimensional maps were constructed depicting the beat-to-beat response. When alternans was observed, a novel numerical clamping protocol was used to determine whether alternans was caused by oscillations in SR calcium loading or by RyR2 refractoriness. Using this protocol, we identified regions of RyR2 gating parameters where SR calcium loading or RyR2 refractoriness underlie the induction of calcium alternans, and we found that at the onset of alternans both mechanisms contribute. At low inactivation rates of the RyR2, calcium alternans was caused by alternation in SR calcium loading, while at low activation rates it was caused by alternation in the level of available RyR2s. Conclusions/Significance We have mapped cardiomyocyte beat-to-beat responses as a function of RyR2 activation and inactivation, identifying domains where SR calcium load or RyR2 refractoriness underlie the induction of calcium alternans. A corollary of this work is that RyR2 refractoriness due to slow recovery from inactivation can be the cause of calcium alternans even when alternation in SR calcium load is present. PMID:23390511

  15. Melatonin and childhood refractory epilepsy--a pilot study.

    PubMed

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

    2010-09-01

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

  16. 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

  17. Combined Endoscopic/Sonographic-Based Risk Matrix Model for Predicting One-Year Risk of Surgery: A Prospective Observational Study of a Tertiary Center Severe/Refractory Crohn's Disease Cohort.

    PubMed

    Rispo, Antonio; Imperatore, Nicola; Testa, Anna; Bucci, Luigi; Luglio, Gaetano; De Palma, Giovanni Domenico; Rea, Matilde; Nardone, Olga Maria; Caporaso, Nicola; Castiglione, Fabiana

    2018-03-08

    In the management of Crohn's Disease (CD) patients, having a simple score combining clinical, endoscopic and imaging features to predict the risk of surgery could help to tailor treatment more effectively. AIMS: to prospectively evaluate the one-year risk factors for surgery in refractory/severe CD and to generate a risk matrix for predicting the probability of surgery at one year. CD patients needing a disease re-assessment at our tertiary IBD centre underwent clinical, laboratory, endoscopy and bowel sonography (BS) examinations within one week. The optimal cut-off values in predicting surgery were identified using ROC curves for Simple Endoscopic Score for CD (SES-CD), bowel wall thickness (BWT) at BS, and small bowel CD extension at BS. Binary logistic regression and Cox's regression were then carried out. Finally, the probabilities of surgery were calculated for selected baseline levels of covariates and results were arranged in a prediction matrix. Of 100 CD patients, 30 underwent surgery within one year. SES-CD©9 (OR 15.3; p<0.001), BWT©7 mm (OR 15.8; p<0.001), small bowel CD extension at BS©33 cm (OR 8.23; p<0.001) and stricturing/penetrating behavior (OR 4.3; p<0.001) were the only independent factors predictive of surgery at one-year based on binary logistic and Cox's regressions. Our matrix model combined these risk factors and the probability of surgery ranged from 0.48% to 87.5% (sixteen combinations). Our risk matrix combining clinical, endoscopic and ultrasonographic findings can accurately predict the one-year risk of surgery in patients with severe/refractory CD requiring a disease re-evaluation. This tool could be of value in clinical practice, serving as the basis for a tailored management of CD patients.

  18. Refractory materials from lunar resources

    NASA Technical Reports Server (NTRS)

    Fabes, B. D.; Poisl, W. H.

    1991-01-01

    Refractories - materials which are able to withstand extremely high temperatures - are sure to be an important part of any processing facility or human outpost which is built on Mars. Containers for processing lunar oxygen will need high temperature components. Fabrication of structural material from lunar resources need both containment vessels to hold high temperature melts and molds in which to form the final shapes. Certainly, it would be desirable to fabricate such vessels and molds on the Moon, rather than carrying them up from the Earth. At first glance, this might appear to be a trivial task, since the Moon's surface consists of a variety of refractory compositions. To turn the regolith into a useful fire brick or mold, however, will require water or other binders and additives which are likely to be in extremely short supply on the Moon. The steps needed to make fire bricks and molds for lunar-derived structural materials are examined, pointing out the critical steps and resources which will be needed. While these processes and applications may seem somewhat mundane, it is emphasized that it is precisely these rudimentary processes which must be mastered before discussing making aerobrakes, and other fancier refractories from lunar resources.

  19. Method of making a composite refractory material

    DOEpatents

    Morrow, M.S.; Holcombe, C.E.

    1995-09-26

    A composite refractory material is prepared by combining boron carbide with furan resin to form a mixture containing about 8 wt. % furan resin. The mixture is formed into a pellet which is placed into a grit pack comprising an oxide of an element such as yttrium to form a sinterable body. The sinterable body is sintered under vacuum with microwave energy at a temperature no greater than 2000 C to form a composite refractory material.

  20. 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.

  1. Refractory myasthenia gravis – clinical profile, comorbidities and response to rituximab

    PubMed Central

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

    2016-01-01

    Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27–53 years. In our study 25 patients (32.89%) belonged to the age group of 21–30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% (p=3.3x10–8) to 94.6% (p=2.2x10–14) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low. PMID:27790079

  2. Spent refractory reuse as a slag conditioning additive in the EAF

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

    Bennett, James P.; Kwong, Kyei-Sing; Krabbe, Rick

    2000-01-01

    Refractories removed from service in EAF applications are typically landfilled. A joint USDOE and Steel Manufacturers Association program involving industrial cooperators is evaluating spent refractory recycling/reuse. A review of current recycling practices and a review of progress towards controlling EAF slag chemistry and properties with the additions of basic spent refractories will be discussed.

  3. Risk of Recurrent or Refractory Strictures and Outcome of Endoscopic Dilation for Radiation-Induced Esophageal Strictures

    PubMed Central

    Agarwalla, Anant; Small, Aaron J.; Mendelson, Aaron H.; Scott, Frank I.; Kochman, Michael L.

    2014-01-01

    Background Radiation therapy for head, neck, and esophageal cancer can result in esophageal strictures that may be difficult to manage. Radiation-induced esophageal strictures often require repeat dilation to obtain relief of dysphagia. This study aimed to determine the long-term clinical success and rates of recurrent and refractory stenosis in patients with radiation-induced strictures undergoing dilation. Methods Retrospective cohort study of patients with radiation-induced strictures who underwent endoscopic dilation by a single provider from October 2007– October 2012. Outcomes measured included long-term clinical efficacy, interval between sessions, number of dilations, and proportion of radiation strictures that were recurrent or refractory. Risk factors for refractory strictures were assessed. Results 63 patients underwent 303 dilations. All presented with a stricture > 30 days after last radiation session. Clinical success to target diameter was achieved in 52 patients (83%). A mean of 3.3 (+/− 2.6) dilations over a median period of 4 weeks was needed to achieve initial patency. Recurrence occurred in 17 (33%) at a median of 22 weeks. Twenty-seven strictures (43%) were refractory to dilation therapy. Fluoroscopy during dilation (OR, 22.88; 95% CI, 3.19 – 164.07), severe esophageal stenosis (lumen <9 mm) (OR, 10.51; 95% CI, 1.94 – 56.88), and proximal location with prior malignancy extrinsic to the lumen (OR, 6.96; 95% CI, 1.33 – 36.29) were independent predictors of refractory strictures in multivariate analysis. Conclusions 1. Radiation-induced strictures have a delayed onset (>30 days) from time of radiation injury. 2. Endoscopic dilation can achieve medium-term luminal remediation but the strictures have a high long-term recurrence rate of up to 33%. 3. Remediation of radiation strictures following laryngectomy can be achieved but require frequent dilations. 4. Clinical and procedural predictors may identify patients at high risk of refractory

  4. 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

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

    PubMed Central

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

    2014-01-01

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

  6. Association between sex, nutritional status, severity of dengue hemorrhagic fever, and immune status in infants with dengue hemorrhagic fever.

    PubMed

    Nguyen, Thanh Hung; Nguyen, Trong Lan; Lei, Huan-Yao; Lin, Yee-Shin; Le, Bich Lien; Huang, Kao-Jean; Lin, Chiou-Feng; Do, Quang Ha; Vu, Thi Que Huong; Lam, Thi My; Yeh, Trai-Ming; Huang, Jyh-Hsiung; Liu, Ching-Chuan; Halstead, Scott B

    2005-04-01

    The association between sex, nutritional status, and the severity of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), and immune status was investigated in 245 Vietnamese infants with predominantly primary infections with dengue virus. Male and female infants were at equal risk of developing DHF/DSS. However, infants of low height and weight for age were under-represented among DHF/DSS cases compared with 533 healthy baby clinic infant controls. Acute illness phase blood levels of selected cytokines (interferon-gamma and tumor necrosis factor-alpha) and serum levels of antibodies to dengue virus were elevated in the same range in male and female infants with DHF/DSS, as well as in infants with and without malnutrition.

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

    PubMed

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

    2009-04-01

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

  8. Next-Step Strategies for Panic Disorder Refractory to Initial Pharmacotherapy

    PubMed Central

    Simon, NM; Otto, MW; Worthington, JJ; Hoge, EA; Thompson, EH; LeBeau, RT; Moshier, SJ; Zalta, AK; Pollack, MH

    2010-01-01

    Background More data is needed to guide next step interventions for panic disorder refractory to initial intervention. Method This 24-week randomized clinical trial (RCT) consisted of three phases. Phase 1 is a 6-week lead-in with open-label sertraline flexibly dosed to 100mg (or escitalopram equivalent) to prospectively define treatment refractoriness (lack of remission). Phase 2 is a six-week double blind RCT of (1) increased dose serotonin selective reuptake inhibitor (SSRI) versus (2) continued SSRI plus placebo. Phase 3 is a 12-week RCT of added cognitive-behavioral therapy (CBT) compared to “medication-optimization” (MO) with SSRI plus clonazepam. Primary endpoints were remission and change in Panic Disorder Severity Scale (PDSS) score in the intent to treat sample in each phase. Results In Phase 1, 20.5% (8/39) achieved remission, and only baseline severity predicted endpoint PDSS (β (SE)= 1.04(0.15), t=6.76, p<0.000). In Phase 2, increasing the SSRI dose did not result in greater improvement or remission rates (placebo 15% [n=2] vs. increased dose 9%[n=1]: FET p=n.s.). In Phase 3, remission was minimal (MO = 11%; CBT =10%), with a lack of group difference in PDSS reduction (t(df)=0.51(17), p>0.60) consistent with a small effect size (d=0.24). Conclusion Although power was limited and larger studies are needed, we failed to find evidence for greater benefit of increased SSRI dose versus continuation of current dose for panic disorder symptomatic after 6 weeks at moderate dose. Further, augmentation with CBT or medication optimization with clonazepam augmentation in non-remitted panic after 12 weeks of an SSRI did not differ, suggesting both are reasonable next-step options. However, low overall remission rates in this comorbid refractory population suggest better predictors of response to specific treatments over time and additional interventions are needed. PMID:19814948

  9. Method of making a composite refractory material

    DOEpatents

    Morrow, Marvin S.; Holcombe, Cressie E.

    1995-01-01

    A composite refractory material is prepared by combining boron carbide with furan resin to form a mixture containing about 8 wt. % furan resin. The mixture is formed into a pellet which is placed into a grit pack comprising an oxide of an element such as yttrium to form a sinterable body. The sinterable body is sintered under vacuum with microwave energy at a temperature no greater than 2000.degree. C. to form a composite refractory material.

  10. Office Procedures in Refractory Chronic Rhinosinusitis.

    PubMed

    Thamboo, Andrew; Patel, Zara M

    2017-02-01

    Office procedures in chronic rhinosinusitis (CRS) can be considered before and after medical management, as well as before and after surgical management. This article focuses specifically on refractory CRS, meaning those patients who have failed medical and surgical management already. The options available in the management of refractory CRS depend on the personnel, equipment, and instrumentation available in the office setting; surgeon experience; and patient suitability and tolerability. This article provides readers with possible procedural options that can be done in their clinics with indications, patient selection, potential complications, and postoperative considerations. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Composition and process for making an insulating refractory material

    DOEpatents

    Pearson, Alan; Swansiger, Thomas G.

    1998-04-28

    A composition and process for making an insulating refractory material. The composition includes calcined alumina powder, flash activated alumina powder, an organic polymeric binder and a liquid vehicle which is preferably water. Starch or modified starch may also be added. A preferred insulating refractory material made with the composition has a density of about 2.4-2.6 g/cm.sup.3 with reduced thermal conductivity, compared with tabular alumina. Of importance, the formulation has good abrasion resistance and crush strength during intermediate processing (commercial sintering) to attain full strength and refractoriness, good abrasion resistance and crush strength.

  12. Impact of social factors on the quality of life of patients with refractory epilepsy.

    PubMed

    Viteva, E

    2013-06-01

    To assess the impact of social factors on the quality of life of Bulgarian patients with refractory epilepsy. We have studied 70 patients with refractory epilepsy (RE) and 70 patients with pharmacosensitive epilepsy. All of them were between 18 and 65 years of age, without cognitive decline, progressive somatic or neurological disease or recent seizures. All participants were inquired about their education,employment, marital status, and driving. Only the patients with RE completed QOLIE-89. Twenty-five (35.71%) of the participants with RE were not married; 16 (22.86%) of them had an elementary education, 44 (62.86%) - a secondary education, and 10 (14.29%) - a university education.Nineteen (27.4%) participants were employed, 41 (58.57%) were recognized disabled, 10 (14.29%)were unemployed. Two (2.86%) of the patients with RE were drivers. We found out that the marital status did not change the quality of life. The university education correlated with a higher assessment of the “overall health” subscale (50%). The limited or lacking employment had a negative impact on the assessment of the following subscales: “pain”, “health discouragement”, “sexual relations”, “emotional well-being”, “memory”, “work/driving/social function”, “overall health”, “overall quality of life” and the overall score of QOLIE-89. The possibility of driving correlated with more worries about adverse events from antiepileptic drugs. The limited or lacking employment has a negative impact on most aspects of the quality of life, while education and driving influence single aspects of the quality of life.

  13. Resistant and Refractory Hypertension: Antihypertensive Treatment Resistance vs Treatment Failure

    PubMed Central

    Siddiqui, Mohammed; Dudenbostel, Tanja; Calhoun, David A.

    2017-01-01

    Resistant or difficult to treat hypertension is defined as high blood pressure that remains uncontrolled with 3 or more different antihypertensive medications, including a diuretic. Recent definitions also include controlled blood pressure with use of 4 or more medications as also being resistant to treatment. Recently, refractory hypertension, an extreme phenotype of antihypertensive treatment failure has been defined as hypertension uncontrolled with use of 5 or more antihypertensive agents, including a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Patients with resistant vs refractory hypertension share similar characteristics and comorbidities, including obesity, African American race, female sex, diabetes, coronary heart disease, chronic kidney disease, and obstructive sleep apnea. Patients with refractory vs resistant hypertension tend to be younger and are more likely to have been diagnosed with congestive heart failure. Refractory hypertension might also differ from resistant hypertension in terms of underlying cause. Preliminary evidence suggests that refractory hypertension is more likely to be neurogenic in etiology (ie, heightened sympathetic tone), vs a volume-dependent hypertension that is more characteristic of resistant hypertension in general. PMID:26514749

  14. 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.

  15. 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.

  16. 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.

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

    PubMed

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

    2014-12-01

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

  18. White-Coat Effect Is Uncommon in Patients With Refractory Hypertension.

    PubMed

    Siddiqui, Mohammed; Judd, Eric K; Oparil, Suzanne; Calhoun, David A

    2017-09-01

    Refractory hypertension is a recently described phenotype of antihypertensive treatment failure defined as uncontrolled blood pressure (BP) despite the use of ≥5 different antihypertensive agents, including chlorthalidone and spironolactone. Recent studies indicate that refractory hypertension is uncommon, with a prevalence of ≈5% to 10% of patients referred to a hypertension specialty clinic for uncontrolled hypertension. The prevalence of white-coat effect, that is, uncontrolled automated office BP ≥135/85 mm Hg and controlled out-of-office BP <135/85 mm Hg, by awake ambulatory BP monitor in hypertensive patients overall is ≈30% to 40%. The prevalence of white-coat effect among patients with refractory hypertension has not been previously reported. In this prospective evaluation, consecutive patients referred to the University of Alabama at Birmingham Hypertension Clinic for uncontrolled hypertension were enrolled. Refractory hypertension was defined as uncontrolled automated office BP ≥135/85 mm Hg with the use of ≥5 antihypertensive agents, including chlorthalidone and spironolactone. Automated office BP measurements were based on 6 serial readings, done automatically with the use of a BpTRU device unobserved in the clinic. Out-of-office BP measurements were done by 24-hour ambulatory BP monitor. Thirty-four patients were diagnosed with refractory hypertension, of whom 31 had adequate ambulatory BP monitor readings. White-coat effect was present in only 2 patients, or 6.5% of the 31 patients with refractory hypertension, suggesting that white-coat effect is largely absent in patients with refractory hypertension. These findings suggest that white-coat effect is not a common cause of apparent lack of BP control in patients failing maximal antihypertensive treatment. © 2017 American Heart Association, Inc.

  19. Molecular-level dynamics of refractory dissolved organic matter

    NASA Astrophysics Data System (ADS)

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

    2012-04-01

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

  20. Prefabricated Refractory Panels for Use in KSC's Flame Deflectors: A Feasibility Study

    NASA Technical Reports Server (NTRS)

    Calle, Luz Maria; Trejo, David

    2010-01-01

    The launch complexes at the John F. Kennedy Space Center (KSC) have been used to launch space vehicles for the Apollo and Space Shuttle programs. NASA is currently designing and developing a new space vehicle. The launch complexes have been in service for a significant duration and the aggressive conditions of the Florida coast and the launches have resulted in failures within the launch complexes. Of particular interests is the performance of the refractory lining that covers the steel base structure for the diversion of the exhaust from the launched vehicles (i.e., the flame deflectors). An unprotected steel base structure would likely experience loss of strength and possible failure when subjected to the high temperatures during launches. The refractory lining is critical for successful launches. The refractory material currently used in the flame trenches was developed in 1959 and is the only refractory material approved for use in these facilities. Significant effort and costs are expended in repairing the lining system after each launch. NASA is currently performing a comprehensive research program to assess and develop refractory materials for improved performance in the flame trenches. However, one challenge associated with the use of refractory materials in the flame trench is that the materials should be cured, dried, and fired to maximize their properties and characteristics. Because of the large size of the deflectors and trenches, drying and firing of the lining system is difficult, if not impossible. Most refractory materials are dried and fired before use. Because the refractory materials used for the deflector lining cannot be dried and fired, the full potential of the materials are not being realized. A system that could use refractory materials that could be cured, dried, and sintered in a controlled environment would likely improve the performance of the lining system. This report evaluates the feasibility of fabricating and placing prefabricated

  1. Lenvatinib in Advanced Radioiodine-Refractory Thyroid Cancer - A Retrospective Analysis of the Swiss Lenvatinib Named Patient Program.

    PubMed

    Balmelli, Catharina; Railic, Nikola; Siano, Marco; Feuerlein, Kristin; Cathomas, Richard; Cristina, Valerie; Güthner, Christiane; Zimmermann, Stefan; Weidner, Sabine; Pless, Miklos; Stenner, Frank; Rothschild, Sacha I

    2018-01-01

    Purpose: Differentiated thyroid cancer (DTC) accounts for approximately 95% of thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has very limited efficacy and is associated with substantial toxicity. With increasing knowledge of the molecular pathogenesis of DTC, novel targeted therapies have been developed. Lenvatinib is a tyrosine kinase inhibitor (TKI) with promising clinical activity based on the randomized phase III SELECT trial. In Switzerland, a Named Patient Program (NPP) was installed to bridge the time gap to Swissmedic approval. Here, we report the results from the Swiss Lenvatinib NPP including patients with metastatic RAI-refractory DTC. Methods: Main inclusion criteria for the Swiss NPP were RAI-refractory DTC, documented disease progression, Eastern Cooperative Oncology Group (ECOG) performance status 0-3. The number of previous therapies was not limited. The Swiss Lenvatinib NPP was initiated in June 2014 and was closed in October 2015 with the approval of the drug. Results: Between June 2014 and October 2015, 13 patients with a median age of 72 years have been enrolled. Most patients (69%) had at least one prior systemic therapy, mainly sorafenib. 31% of patients showed a PR and 31% SD. Median progression free survival was 7.2 months and the median overall survival was 22.7 months. Dose reduction due to adverse events was necessary in 7 patients (53%). At the time of analysis 6 patients (47%) were still on treatment with a median time on treatment of 9.98 months. Conclusions: Our results show that lenvatinib has reasonable clinical activity in unselected patients with RAI-refractory thyroid cancer with nearly two-third of patients showing clinical benefit. The toxicity profile of lenvatinib is manageable.

  2. Lenvatinib in Advanced Radioiodine-Refractory Thyroid Cancer - A Retrospective Analysis of the Swiss Lenvatinib Named Patient Program

    PubMed Central

    Balmelli, Catharina; Railic, Nikola; Siano, Marco; Feuerlein, Kristin; Cathomas, Richard; Cristina, Valerie; Güthner, Christiane; Zimmermann, Stefan; Weidner, Sabine; Pless, Miklos; Stenner, Frank; Rothschild, Sacha I.

    2018-01-01

    Purpose:Differentiated thyroid cancer (DTC) accounts for approximately 95% of thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has very limited efficacy and is associated with substantial toxicity. With increasing knowledge of the molecular pathogenesis of DTC, novel targeted therapies have been developed. Lenvatinib is a tyrosine kinase inhibitor (TKI) with promising clinical activity based on the randomized phase III SELECT trial. In Switzerland, a Named Patient Program (NPP) was installed to bridge the time gap to Swissmedic approval. Here, we report the results from the Swiss Lenvatinib NPP including patients with metastatic RAI-refractory DTC. Methods:Main inclusion criteria for the Swiss NPP were RAI-refractory DTC, documented disease progression, Eastern Cooperative Oncology Group (ECOG) performance status 0-3. The number of previous therapies was not limited. The Swiss Lenvatinib NPP was initiated in June 2014 and was closed in October 2015 with the approval of the drug. Results:Between June 2014 and October 2015, 13 patients with a median age of 72 years have been enrolled. Most patients (69%) had at least one prior systemic therapy, mainly sorafenib. 31% of patients showed a PR and 31% SD. Median progression free survival was 7.2 months and the median overall survival was 22.7 months. Dose reduction due to adverse events was necessary in 7 patients (53%). At the time of analysis 6 patients (47%) were still on treatment with a median time on treatment of 9.98 months. Conclusions:Our results show that lenvatinib has reasonable clinical activity in unselected patients with RAI-refractory thyroid cancer with nearly two-third of patients showing clinical benefit. The toxicity profile of lenvatinib is manageable. PMID:29344270

  3. 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.

  4. Variation in Anticonvulsant Selection and Electroencephalographic Monitoring Following Severe Traumatic Brain Injury in Children-Understanding Resource Availability in Sites Participating in a Comparative Effectiveness Study.

    PubMed

    Kurz, Jonathan E; Poloyac, Samuel M; Abend, Nicholas S; Fabio, Anthony; Bell, Michael J; Wainwright, Mark S

    2016-07-01

    Early posttraumatic seizures may contribute to worsened outcomes after traumatic brain injury. Evidence to guide the evaluation and management of early posttraumatic seizures in children is limited. We undertook a survey of current practices of continuous electroencephalographic monitoring, seizure prophylaxis, and the management of early posttraumatic seizures to provide essential information for trial design and the development of posttraumatic seizure management pathways. Surveys were sent to site principal investigators at all 43 sites participating in the Approaches and Decisions in Acute Pediatric TBI trial at the time of the survey. Surveys consisted of 12 questions addressing strategies to 1) implement continuous electroencephalographic monitoring, 2) posttraumatic seizure prophylaxis, 3) treat acute posttraumatic seizures, 4) treat status epilepticus and refractory status epilepticus, and 5) monitor antiseizure drug levels. Institutions comprised a mixture of free-standing children's hospitals and university medical centers across the United States and Europe. Site principal investigators of the Approaches and Decisions in Acute Pediatric TBI trial. None. Continuous electroencephalographic monitoring was available in the PICU in the overwhelming majority of clinical sites (98%); however, the plans to operationalize such monitoring for children varied considerably. A similar majority of sites report that administration of prophylactic antiseizure medications is anticipated in children (93%); yet, a minority reports that a specified protocol for treatment of posttraumatic seizures is in place (43%). Reported medication choices varied substantially between sites, but the majority of sites reported pentobarbital for refractory status epilepticus (81%). The presence of treatment protocols for seizure prophylaxis, early posttraumatic seizures, posttraumatic status epilepticus, and refractory status epilepticus was associated with decreased reported medications

  5. Phenobarbital for Neonatal Seizures: Response Rate and Predictors of Refractoriness.

    PubMed

    Spagnoli, Carlotta; Seri, Stefano; Pavlidis, Elena; Mazzotta, Silvia; Pelosi, Annalisa; Pisani, Francesco

    2016-10-01

    Background Phenobarbital is the first-line choice for neonatal seizures treatment, despite a response rate of approximately 45%. Failure to respond to acute anticonvulsants is associated with poor neurodevelopmental outcome, but knowledge on predictors of refractoriness is limited. Objective To quantify response rate to phenobarbital and to establish variables predictive of its lack of efficacy. Methods We retrospectively evaluated newborns with electrographically confirmed neonatal seizures admitted between January 1999 and December 2012 to the neonatal intensive care unit of Parma University Hospital (Italy), excluding neonates with status epilepticus. Response was categorized as complete (cessation of clinical and electrographic seizures after phenobarbital administration), partial (reduction but not cessation of electrographic seizures with the first bolus, response to the second bolus), or absent (no response after the second bolus). Multivariate analysis was used to identify independent predictors of refractoriness. Results Out of 91 newborns receiving phenobarbital, 57 (62.6%) responded completely, 15 (16.5%) partially, and 19 (20.9%) did not respond. Seizure type (p = 0.02), background electroencephalogram (EEG; p ≤ 0.005), and neurologic examination (p  ≤  0.005) correlated with response to phenobarbital. However, EEG (p  ≤  0.02) and seizure type (p  ≤  0.001) were the only independent predictors. Conclusion Our results suggest a prominent role of neurophysiological variables (background EEG and electrographic-only seizure type) in predicting the absence of response to phenobarbital in high-risk newborns. Georg Thieme Verlag KG Stuttgart · New York.

  6. Characterization of refractory brick based on local raw material from Lampung Province - Indonesia

    NASA Astrophysics Data System (ADS)

    Amin, Muhammad; Suryana, Yayat I.; Isnugroho, Kusno; Aji, Bramantyo B.; Birawidha, David C.; Hendronursito, Yusup

    2018-04-01

    Refractories are non-metallic inorganic materials that are difficult to melt at high temperatures and used in high-temperature casting industries. Refractories are classified into their constituent mineral feed stocks, refractories having typical plot properties commonly called fire bricks. In the manufacture of refractory bricks that exist in the market during the use of mangrove materials derived from abroad that is from China. In this research the refractory brick materials used are quartz sand, feldspart, kaolin, bentonite, and ball clay. All materials come from local Lampung Province - Indonesia. The experiment, there are 7 kinds of experimental composition, made of plot shape with size 230 mm, 65 mm in thickness, 114 mm height mould using manual press machine with 10 tons power and burning at 1400°C for 5 hours. Refractory brick product is done by physical test in the form of porosity, specific gravity, compressive strength and XRF and SEM characteristics. The result of XRF characteristic of refractory brick composition of 1 to 5 compared to the refractory brick type SK 34 in the market and the result of composition 1 is a composition close to refractory brick composition type SK 34 namely SiO2 is 54.21 %, Al2O3 is 25.38 % and test Physical of Bulk density is 2.25 g/cm3, porosity is 18.98 % and compressive strength is 325 kg/cm2.

  7. Synthetic Coal Slag Infiltration into Varying Refractory Materials

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

    Kaneko, Tetsuya K; Thomas, Hugh; Bennett, James P

    The infiltrations of synthetic coal slag into 99%Al{sub 2}O{sub 3}, 85%Al{sub 2}O{sub 3}–15%SiO{sub 2}, and 90%Cr{sub 2}O{sub 3}–10%Al{sub 2}O{sub 3} refractories with a temperature gradient induced along the penetration direction were compared to one another. The infiltrating slag was synthesized with a composition that is representative of an average of the ash contents from U S coal feedstock. Experiments were conducted with a hot-face temperature of 1450°C in a CO/CO{sub 2} atmosphere. Minimal penetration was observed in the 90%Cr{sub 2}O{sub 3}–10%Al{sub 2}O{sub 3} material because interactions between the refractory and the slag produced a protective layer of FeCr{sub 2}O{sub 4},more » which impeded slag flow into the bulk of the refractory. After 5 h, the 99%Al{sub 2}O{sub 3} sample exhibited an average penetration of 12.7 mm whereas the 85%Al{sub 2}O{sub 3}–15%SiO{sub 2} sample showed 3.8 mm. Slag infiltrated into the 99%Al{sub 2}O{sub 3} and 85%Al{sub 2}O{sub 3}–15%SiO{sub 2} refractory systems by dissolving the respective refractories' matrix materials, which consist of fine Al{sub 2}O{sub 3} particles and an amorphous alumino-silicate phase. Due to enrichment in SiO{sub 2}, a network-former, infiltration into the 85%Al{sub 2}O{sub 3}–15%SiO{sub 2} system yielded a higher viscosity slag and hence, a shallower penetration depth. The results suggest that slag infiltration can be limited by interactions with the refractory through the formation of either a solid layer that physically impedes fluid flow or a more viscous slag that retards infiltration.« less

  8. 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

  9. Predictors of severity in childhood pancreatitis: correlation with nutritional status and racial demographics.

    PubMed

    Vasilescu, Alexandra; Cuffari, Carmen; Santo Domingo, Lisa; Scheimann, Ann O

    2015-04-01

    Acute pancreatitis is one of the leading causes of rising pediatric hospitalizations in North America. The aim of this study was to assess the role of nutritional status and racial influences on the severity of acute pancreatitis in children. The institutional review board approved this retrospective chart review of children with the diagnosis of acute pancreatitis between the ages of 0 and 18 years hospitalized at the Johns Hopkins Hospital between 1998 and 2008. Parameters studied included biochemical markers associated with pancreatitis, review of severity of illness reflected through the length of stay, and pediatric intensive care unit admission. The length of in-patient hospitalization was longer for children with imaging findings of pseudocyst or pancreatic necrosis (23.1 ± 26.4 days vs 4.4 ± 10.6 days; P = 0.0074) and malnourished children versus normal weight and obese children (16.5 days for malnourished vs 10.6 days for normal weight vs 10.7 days for obese; P = 0.04). There was also a significant difference in the need for pediatric intensive care unit admission across ethnic groups (18% African American vs 7% white) (P = 0.04). Ethnicity and nutritional status may influence the severity and duration of hospitalization among children with pancreatitis.

  10. 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

  11. Angiotensin II in Refractory Septic Shock.

    PubMed

    Antonucci, Elio; Gleeson, Patrick J; Annoni, Filippo; Agosta, Sara; Orlando, Sergio; Taccone, Fabio Silvio; Velissaris, Dimitrios; Scolletta, Sabino

    2017-05-01

    Refractory septic shock is defined as persistently low mean arterial blood pressure despite volume resuscitation and titrated vasopressors/inotropes in patients with a proven or suspected infection and concomitant organ dysfunction. Its management typically requires high doses of catecholamines, which can induce significant adverse effects such as ischemia and arrhythmias. Angiotensin II (Ang II), a key product of the renin-angiotensin-aldosterone system, is a vasopressor agent that could be used in conjunction with other vasopressors to stabilize critically ill patients during refractory septic shock, and reduce catecholamine requirements. However, very few clinical data are available to support Ang II administration in this setting. Here, we review the current literature on this topic to better understand the role of Ang II administration during refractory septic shock, differentiating experimental from clinical studies. We also consider the potential role of exogenous Ang II administration in specific organ dysfunction and possible pitfalls with Ang II in sepsis. Various issues remain unresolved and future studies should investigate important topics such as: the optimal dose and timing of Ang II administration, a comparison between Ang II and the other vasopressors (epinephrine; vasopressin), and Ang II effects on microcirculation.

  12. 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

  13. 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.

  14. 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.

  15. Vitamin B6 deficiency: a potential cause of refractory seizures in adults.

    PubMed

    Gerlach, Anthony T; Thomas, Sheela; Stawicki, Stanislaw P; Whitmill, Melissa L; Steinberg, Steven M; Cook, Charles H

    2011-03-01

    In children, vitamin B(6) (pyridoxine) deficiency has been described as a cause of seizures that are refractory to conventional antiepileptic medications. We describe the clinical presentation of 3 adults with refractory seizures (later diagnosed with vitamin B(6) deficiency) that resolved after pyridoxine treatment. Case series. Tertiary care surgical intensive care unit. In the first case, a 54-year-old male with history of alcoholic cirrhosis developed new-onset seizures refractory to phenytoin and levetiracetam 8 days after liver transplantation. In the second case, a 59-year-old male with hepatitis C infection developed intracranial hemorrhage and new-onset seizures refractory to phenytoin, levetiracetam, and pentobarbital. The third patient is a 78-year-old male with a history of alcohol dependence who was admitted for an intraventricular bleed and developed new onset of refractory seizures. Intravenous pyridoxine followed by oral pyridoxine. In all 3 cases, seizures persisted despite escalation of conventional antiepileptic medications but resolved within 2 days of pyridoxine supplementation. In each case, low serum pyridoxal 5'-phosphate concentrations normalized with pyroxidine administration. Although refractory seizures caused by vitamin B(6) deficiency are rare in adults, it should be considered in critically ill adult patients with refractory seizures.

  16. Management of severe asthma: targeting the airways, comorbidities and risk factors.

    PubMed

    Gibson, Peter G; McDonald, Vanessa M

    2017-06-01

    Severe asthma is a complex heterogeneous disease that is refractory to standard treatment and is complicated by multiple comorbidities and risk factors. In mild to moderate asthma, the burden of disease can be minimised by inhaled corticosteroids, bronchodilators and self-management education. In severe asthma, however, management is more complex. When patients with asthma continue to experience symptoms and exacerbations despite optimal management, severe refractory asthma (SRA) should be suspected and confirmed, and other aetiologies ruled out. Once a diagnosis of SRA is established, patients should undergo a systematic and multidimensional assessment to identify inflammatory endotypes, risk factors and comorbidities, with targeted and individualised management initiated. We describe a practical approach to assessment and management of patients with SRA. © 2017 Royal Australasian College of Physicians.

  17. 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

  18. 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

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

    PubMed Central

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

    2012-01-01

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

  20. 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

  1. Central Diabetes Insipidus in Refractory Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

    PubMed

    Ohashi, Keiji; Morishita, Michiko; Watanabe, Haruki; Sada, Ken-Ei; Katsuyama, Takayuki; Miyawaki, Yoshia; Katsuyama, Eri; Narazaki, Mariko; Tatebe, Noriko; Watanabe, Katsue; Kawabata, Tomoko; Wada, Jun

    2017-11-01

    We herein describe two cases of refractory antineutrophil cytoplasmic antibody-associated vasculitis (AAV) complicated with diabetes insipidus (DI) possibly related to hypertrophic pachymeningitis (HP). One patient had microscopic polyangiitis and HP, which were refractory to cyclophosphamide, azathioprine, rituximab, mycophenolate mofetil (MMF), and mizoribine. Remission was finally achieved with the use of etanercept, but DI occurred 5 years later. The other patient had granulomatosis with polyangiitis, which that was refractory to cyclophosphamide, methotrexate, MMF, and rituximab. DI subsequently developed, but was successfully treated with etanercept. Dura mater hypertrophy was macroscopically observed in the latter case.

  2. 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.

  3. [Cognitive therapy for patients with refractory irritable bowel syndrome].

    PubMed

    Wang, Weian; Pan, Guozong; Qian, Jiaming

    2002-03-01

    To investigate the procedure and tactics used in the cognitive therapy for patients with irritable bowel syndrome (IBS), and to evaluate the efficacy of cognitive therapy in the treatment of refractory IBS. A self-control study on the cognitive therapy for 22 patients with refractory IBS symptoms (according to Rome II criteria) was performed. The procedure of cognitive therapy included five steps, namely health education, patients' questioning, relaxing training, dissensitization training, and patients' homework for enforcing the effect of former four steps. The effects of cognitive therapy for IBS were evaluated by improvement of symptom-related-anxiety, index of symptom, quality of life specific for IBS and coping. All 22 cases completed cognitive therapy and first follow-up unit (FFU), at the end of FFU, clinical symptoms in all patients improved (P < 0.05), of them, 81.8% improved significantly (P < 0.001); at 12-months-follow-up, complete remission of clinical symptoms occurred in 72.7% (8/11) patients. Comparison of the scores of symptom-related-anxiety, index of symptom, quality of life specific IBS and coping at the end of 1st follow-up unit with that at basal level, the scores of symptom-anxiety, indexes of severity and frequency of symptoms decreased significantly (P < 0.001, respectively); the scores of depression and anxiety in SCL-90 also decreased significantly (P < 0.001). The scores of active coping rose significantly (P = 0.000). IBS-QOL improved significantly (P < 0.05), of them, dysphoria, body image, food avoidence improved very significantly (P < 0.001, respectively). Cognitive therapy for patients with refractory IBS is rational and effective. During cognitive therapy, we should follow the therapeutic procedure and the principle of individuation.

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

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

    Bennett, James P.

    2004-09-01

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

  5. Recent Status Scores for Version 6 of the Addiction Severity Index (ASI-6)

    PubMed Central

    Cacciola, John S.; Alterman, Arthur I; Habing, Brian; McLellan, A. Thomas

    2012-01-01

    Aims To describe the derivation of Recent Status Scores (RSSs) for Version 6 of the Addiction Severity Index (ASI-6). Design 118 ASI-6 recent status items were subjected to nonparametric item response theory (NIRT) analyses followed by confirmatory factor analysis (CFA). Generalizability and concurrent validity of the derived scores were determined. Setting and Participants 607 recent admissions to variety of substance abuse treatment programs constituted the derivation sample; a subset (N = 254) comprised the validity sample. Measurements The ASI-6 interview and a validity battery of primarily self-report questionnaires that included at least one measure corresponding to each of the seven ASI domains were administered. Findings Nine summary scales describing recent status that achieved or approached both high scalability and reliability were derived; one scale for each of six areas (medical, employment/finances, alcohol, drug, legal, psychiatric), and three scales for the family/social area. Intercorrelations among the RSSs also supported the multidimensionality of the ASI-6. Concurrent validity analyses yielded strong evidence supporting the validity of the six of the RSSs (Medical, Alcohol, Drug, Employment, Family/Social Problems, Psychiatric). Evidence was weaker for the Legal, Family/Social Support and Child Problems RSSs. Generalizability analyses of the scales to males versus females and whites versus blacks supported the comparability of the findings with slight exceptions. Conclusions The psychometric analyses to derive Addiction Severity Index-6 Recent Status Scores (RSSs) support the multidimensionality of the ASI-6 (i.e., the relative independence of different life functioning areas), consistent with research on earlier editions of the instrument. In general, the ASI-6 scales demonstrate acceptable scalability, reliability and concurrent validity. While questions remain about the generalizability of some scales to population subgroups, the overall

  6. Pembrolizumab and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

    ClinicalTrials.gov

    2018-05-22

    Lymphocyte-Rich Classical Hodgkin Lymphoma; Recurrent Lymphocyte-Depleted Classical Hodgkin Lymphoma; Recurrent Mixed Cellularity Classical Hodgkin Lymphoma; Recurrent Nodular Sclerosis Classical Hodgkin Lymphoma; Refractory Lymphocyte-Depleted Classical Hodgkin Lymphoma; Refractory Mixed Cellularity Classical Hodgkin Lymphoma; Refractory Nodular Sclerosis Classical Hodgkin Lymphoma

  7. 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.

  8. The impact of depressive and bipolar symptoms on socioeconomic status, core symptoms, function and severity of fibromyalgia.

    PubMed

    Gota, Carmen E; Kaouk, Sahar; Wilke, William S

    2017-03-01

    To evaluate the prevalence of depressive and bipolar symptoms in a cohort of consecutive fibromyalgia (FM) patients seen in a tertiary care center and to determine the relationship between depressive and manic symptoms with FM symptoms, socioeconomic status, severity and function. Three hundred and five FM patients were enrolled; demographic, clinical and questionnaire data were collected. Depressive symptoms were measured by the Patient Health Questionnaire (PHQ-9), manic symptoms by the Mood Disorders Questionnaire (MDQ). The FM cohort had the following characteristics: age 43.53 (11.7) years; 86.5% white; 82.7% female; PHQ-9 ≥ 10, 59.7%, mean 11.9 (7.3); no depression 11.4%, mild 29.1%, moderate 27.5%, moderate severe 17.7%, severe 14%; anxiety 41.6%; 21.3% had either an MDQ score ≥ 7 and/or reported a past diagnosis of bipolar disorder (BD). Increasing levels of depression severity, as well as a positive screen for BD were significantly associated with increasing prevalence and severity of FM symptoms, longer duration of morning stiffness, and increased severity of FM. Increasing levels of depression were significantly associated with increase in prevalence of reported past sexual abuse, and a decline in socioeconomic status, including higher disability and unemployment rates. Patients with severe FM disease activity, high load of symptoms, prolonged morning stiffness, increased disability, lower socioeconomic status and those who take a lot of medications for FM should be evaluated for depressive and manic symptoms. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  9. Method of coating graphite tubes with refractory metal carbides

    DOEpatents

    Wohlberg, C.

    1973-12-11

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

  10. Reliability study of refractory gate gallium arsenide MESFETS

    NASA Technical Reports Server (NTRS)

    Yin, J. C. W.; Portnoy, W. M.

    1981-01-01

    Refractory gate MESFET's were fabricated as an alternative to aluminum gate devices, which have been found to be unreliable as RF power amplifiers. In order to determine the reliability of the new structures, statistics of failure and information about mechanisms of failure in refractory gate MESFET's are given. Test transistors were stressed under conditions of high temperature and forward gate current to enhance failure. Results of work at 150 C and 275 C are reported.

  11. Reliability study of refractory gate gallium arsenide MESFETS

    NASA Astrophysics Data System (ADS)

    Yin, J. C. W.; Portnoy, W. M.

    Refractory gate MESFET's were fabricated as an alternative to aluminum gate devices, which have been found to be unreliable as RF power amplifiers. In order to determine the reliability of the new structures, statistics of failure and information about mechanisms of failure in refractory gate MESFET's are given. Test transistors were stressed under conditions of high temperature and forward gate current to enhance failure. Results of work at 150 C and 275 C are reported.

  12. Fat-Free Mass Index for Evaluating the Nutritional Status and Disease Severity in COPD.

    PubMed

    Luo, Yuwen; Zhou, Luqian; Li, Yun; Guo, Songwen; Li, Xiuxia; Zheng, Jingjing; Zhu, Zhe; Chen, Yitai; Huang, Yuxia; Chen, Rui; Chen, Xin

    2016-05-01

    Despite the high prevalence of weight loss in subjects with COPD, the 2011 COPD management guidelines do not include an index measuring nutritional status. Fat-free mass index (FFMI) can accurately determine the nutritional status of subjects and may be closely correlated with COPD severity. We aimed to determine the nutritional status evaluated by FFMI according to the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) levels in stable subjects with COPD and the association between nutritional status and respiratory symptoms, exercise capacity, and respiratory muscle function. We included 235 stable subjects with COPD in this cross-sectional study. All of the subjects were divided into the 2011 GOLD Groups A, B, C, and D. FFMI (measured by bioelectrical impedance), spirometry (FEV1, percent-of-predicted FEV1, and FEV1/FVC), respiratory muscle function (peak inspiratory and peak expiratory pressures), exercise capacity (6-min walk distance), and dyspnea severity (Modified Medical Research Council dyspnea scale) were measured and compared between the GOLD groups. Malnutrition was identified in 48.5% of subjects and most prevalent in Group D (Group A: 41%, Group B: 41%, Group C: 31%, and Group D: 62%). FFMI was significantly lower in Group D (P < .001), with both sexes considered malnourished. Low FFMI significantly correlated with frequent exacerbation, older age, decreased pulmonary function, 6-min walk distance, peak inspiratory pressure, and worsened dyspnea. FFMI was significantly lower in the emphysema-dominant phenotype and mixed phenotype compared with the normal phenotype and airway-dominant phenotype. A stepwise multiple linear regression analysis identified peak inspiratory pressures and older age as independent predictors of FFMI. Malnutrition is highly prevalent in all COPD groups, particularly in Group D subjects, who warrant special attention for nutritional intervention and pulmonary rehabilitation. FFMI significantly correlated with

  13. Refractories for high alkali environments

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

    Rau, A.W.; Cloer, F.

    1996-12-31

    Information on refractories for high alkali environments is outlined. Information is presented on: product gallery; alkali attack; chemical reactions; basic layout of alkali cup test; criteria for rating alkali cup test samples; and basic layout of physical properties test.

  14. Antiangiogenic therapy for patients with aggressive or refractory advanced non-small cell lung cancer in the second-line setting.

    PubMed

    Reck, Martin; Garassino, Marina Chiara; Imbimbo, Martina; Shepherd, Frances A; Socinski, Mark A; Shih, Jin-Yuan; Tsao, Anne; Lee, Pablo; Winfree, Katherine B; Sashegyi, Andreas; Cheng, Rebecca; Varea, Rocio; Levy, Benjamin; Garon, Edward

    2018-06-01

    A majority of patients with advanced or metastatic non-small cell lung cancer (NSCLC) will experience disease progression after first-line therapy. Patients who have advanced NSCLC that is especially aggressive, which is defined as disease that rapidly progresses on first-line treatment or disease that is refractory to first-line treatment, have a critical unmet medical need. These patients have a poor prognosis in the second-line setting. Several studies have recently shown that treatment with an antiangiogenic therapy may benefit these patients. This review summarizes the approved antiangiogenic therapies for the treatment of patients with advanced NSCLC in the second-line setting, specifically focusing on the outcomes from subgroups of patients with rapidly progressing or refractory disease. Several antiangiogenic agents, as monotherapy or in combination with other treatments, have been or are currently being studied in patients with advanced NSCLC. Antiangiogenics that are approved for use in patients with advanced NSCLC are limited to bevacizumab in combination with chemotherapy (nonsquamous NSCLC), ramucirumab in combination with docetaxel (all histologies), and nintedanib in combination with docetaxel (adenocarcinoma histology). This review focuses on the efficacy, safety, and quality of life outcomes in the subpopulation of patients with rapidly progressing or refractory NSCLC treated with approved antiangiogenic therapies in the second-line setting. We also discuss the impact of newly approved immunotherapy agents on the outcomes of patients with aggressive or refractory disease. Studies in progress and planned future research will determine if combination treatment with antiangiogenics and immunotherapies will benefit patients with aggressive, advanced NSCLC. Copyright © 2018. Published by Elsevier B.V.

  15. A systematic review of the nutritional status of women of a childbearing age with severe mental illness.

    PubMed

    McColl, Helen; Dhillon, Manpreet; Howard, Louise M

    2013-02-01

    Little is known about the nutritional status of pregnant women with severe mental illness. We therefore carried out a systematic review to investigate whether pregnant women and childbearing aged women with severe mental illness have significantly greater nutritional deficiencies compared with pregnant women and childbearing aged women with no mental illness. We carried out a search using MEDLINE, EMBASE and PsycINFO from January 1980 to January 2011 for studies on nutritional status of childbearing aged women with psychotic disorders. Identification of papers and quality rating of papers (using a modified version of the Newcastle-Ottawa scale) was carried out by two reviewers independently. We identified and screened 4,130 potentially relevant studies from the electronic databases. Fifteen studies met the inclusion criteria (n = 587 women). There were no studies of pregnant women. There was some evidence of low serum folate and vitamin B(12) levels and elevated homocysteine levels in childbearing aged women with psychotic disorders. Further research into the nutritional status of childbearing aged women with severe mental illness is needed. Maternal nutrition has a profound impact on foetal outcome, is a modifiable risk factor and therefore needs prioritising in the care of all childbearing aged women with severe mental illness.

  16. Central Diabetes Insipidus in Refractory Antineutrophil Cytoplasmic Antibody-associated Vasculitis

    PubMed Central

    Ohashi, Keiji; Morishita, Michiko; Watanabe, Haruki; Sada, Ken-Ei; Katsuyama, Takayuki; Miyawaki, Yoshia; Katsuyama, Eri; Narazaki, Mariko; Tatebe, Noriko; Watanabe, Katsue; Kawabata, Tomoko; Wada, Jun

    2017-01-01

    We herein describe two cases of refractory antineutrophil cytoplasmic antibody-associated vasculitis (AAV) complicated with diabetes insipidus (DI) possibly related to hypertrophic pachymeningitis (HP). One patient had microscopic polyangiitis and HP, which were refractory to cyclophosphamide, azathioprine, rituximab, mycophenolate mofetil (MMF), and mizoribine. Remission was finally achieved with the use of etanercept, but DI occurred 5 years later. The other patient had granulomatosis with polyangiitis, which that was refractory to cyclophosphamide, methotrexate, MMF, and rituximab. DI subsequently developed, but was successfully treated with etanercept. Dura mater hypertrophy was macroscopically observed in the latter case. PMID:28943556

  17. 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

  18. 269 Refractory Chronic Urticaria Treated with Omalizumab

    PubMed Central

    Saenz, Martinez; Del Pozo, Ramírez; JJ, Lopez Tiro; Vera, Javier Gomez

    2012-01-01

    Background Chronic urticaria (CU) is a common disorder characterized by recurrent episodes of urticaria pruritic erythematous lesions, associated with angioedema1. It affects 0.1% of the population, it is estimated that approximately 15 to 25% of the population will have hives at some point in their lives.2 About 80% of UC patients are diagnosed as idiopathic chronic urticaria and that no cause is identified, 3 experiencing deterioration in their quality of life affecting your work, social relationships, schemes requiring multiple medications and doses higher than usual. This study proposes Omalizumab (anti-IgE humanized antibody) as a treatment for Refractory Chronic Urticaria (RCU) Object Demonstrate Omalizumab's effectiveness in the treatment of Refractory Chronic Urticaria. Methods A clinical study, was carried out to evaluate the effectiveness of the Omalizumab's treatment on RCU diagnosed patient, including male and female patients ages 12 to 50 diagnosed with RCU, with Scorad higher tan 30 points. We made a questionnaire to know about the patient's family background, skin symptoms beginning, administration of drugs such sistemic steroids, inmunosupresors, calceurine inhibitors, presence of inmunotherapy and age of start. Omalizumab was administered on doses according patient's weight and IgE levels, bimonthly or monthly according to treatment guides. Severeness level was calculated with scorad every 1 month, with IgE seric level measurement and life quality questionnaire. Results 5 patients diagnosed with RCU were included in the group of Omalizumab and 5 patients in the control group (placebo). All patients were female. A gradual decrease on the life quality score and in Score, with a significant P under 0.05 was observed on all patients treated with omalizumab compared with patient in the group with placebo. Conclusions Treatment with Omalizumab progressively decreases the severeness level on RCU, with a significant improvement on the patient's life

  19. Reuse of ultrafine mineral wool production waste in the manufacture of refractory concrete.

    PubMed

    Stonys, R; Kuznetsov, D; Krasnikovs, A; Škamat, J; Baltakys, K; Antonovič, V; Černašėjus, O

    2016-07-01

    The paper deals with the mineral wool production waste (cupola dust - CD), presents CD characterization and aims to reuse CD in production of refractory concrete with calcium aluminate cement. The study of CD covers its chemical, phase and thermal analyses along with the morphological study and determination of particles size distribution. Zeta-potential, electrical conductivity and pH values of CD suspension are presented in the paper as well. Commercial microsilica additive in refractory concrete has been replaced with cupola dust. Compositions of refractory concrete have been prepared by incorporating 1%, 2% and 3% of CD. The bulk density, ultrasonic wave velocity, cold crushing strength and thermal shock resistance of the created refractory concrete have been determined. Based on experimental results, it has been found that cupola dust may be used for the production of refractory concrete. The environmental impact related to the CD reuse in refractory concrete production has been evaluated as well. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. 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

  1. Children with atopic dermatitis in Daejeon, Korea: individualized nutrition intervention for disease severity and nutritional status.

    PubMed

    Kim, Seong Hee; Lee, Jae Ho; Ly, Sun Yung

    2016-12-01

    Atopic dermatitis is one of the most common pediatric chronic inflammatory skin diseases, and certain food allergens and nutrients are closely related to the development and severity of atopic dermatitis. While avoidance of the causative foods is considered the mainstay of treatment, unverified excessive restriction might induce unnecessary limitations in the food intake, consequently leading to nutritional deficiencies and poor growth. This study aimed to identify the characteristics and nutrient intake status in children with atopic dermatitis and to investigate the effects of individualized nutrition intervention. We retrospectively reviewed electronic medical records of 77 pediatric patients with atopic dermatitis who received 4 months of individualized nutrition intervention combined with an elimination diet. The patient characteristics, nutrient intake status, and clinical status were examined before and after the intervention. Before the intervention, 5 children had a weight for height z-score below -2.0, and 48.1% had experienced food restriction; these children showed a significantly higher SCORing of Atopic Dermatitis index than those without experiences, with the number of restricted foods before the intervention positively correlating with the disease severity. The intakes of n-6 and n-3 fatty acids, calcium, folate, and vitamin D were lower than the recommended nutrient intakes for Koreans. After the intervention, the weight for height z-score of 35 children was significantly increased and their SCORing of Atopic Dermatitis index was significantly reduced (p<0.05). Individualized nutrition intervention appears useful for alleviating the severity of atopic dermatitis and improving the growth status by improving the nutrient intake.

  2. Evaluation of Alternative Refractory Materials for the Main Flame Deflectors at KSC Launch Complexes

    NASA Technical Reports Server (NTRS)

    Calle, Luz Marina; Trejo, David; Rutkowsky, Justin

    2006-01-01

    The deterioration of the refractory materials used to protect the KSC launch complex steel base structures from the high temperatures during launches results in frequent and costly repairs and safety hazards. KSC-SPEC-P-0012, Specification for Refractory Concrete, is ineffective in qualifying refractory materials. This study of the specification and of alternative refractory materials recommends a complete revision of the specification and further investigation of materials that were found to withstand the environment of the Solid Rocket Booster main flame deflector better than the refractory materials in current use in terms of compressive strength, tensile strength, modulus of rupture, shrinkage, and abrasion.

  3. Fibrous refractory composite insulation. [shielding reusable spacecraft

    NASA Technical Reports Server (NTRS)

    Leiser, D. B.; Goldstein, H. E.; Smith, M. (Inventor)

    1979-01-01

    A refractory composite insulating material was prepared from silica fibers and aluminosilicate fibers in a weight ratio ranging from 1:19 to 19:1, and about 0.5 to 30% boron oxide, based on the total fiber weight. The aluminosilicate fiber and boron oxide requirements may be satisfied by using aluminoborosilicate fibers and, in such instances, additional free boron oxide may be incorporated in the mix up to the 30% limit. Small quantities of refractory opacifiers, such as silicon carbide, may be also added. The composites just described are characterized by the absence of a nonfibrous matrix.

  4. 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

  5. Evidence for Tocilizumab as a Treatment Option in Refractory Uveitis Associated with Juvenile Idiopathic Arthritis.

    PubMed

    Tappeiner, Christoph; Mesquida, Marina; Adán, Alfredo; Anton, Jordi; Ramanan, Athimalaipet V; Carreno, Ester; Mackensen, Friederike; Kotaniemi, Kaisu; de Boer, Joke H; Bou, Rosa; de Vicuña, Carmen García; Heiligenhaus, Arnd

    2016-12-01

    To report on experience using the anti-interleukin 6 receptor antibody tocilizumab (TCZ) to treat severe and therapy-refractory uveitis associated with juvenile idiopathic arthritis (JIA). Retrospective data were gathered from patients with JIA receiving TCZ treatment for uveitis. JIA and related uveitis data (disease onset, activity, structural complications, and topical and systemic antiinflammatory treatment) were evaluated at the start of TCZ (baseline) and every 3 months during TCZ therapy. A total of 17 patients (14 women) with active uveitis were included (mean age 15.3 ± 6.9 yrs, mean followup time 8.5 mos). In all patients, uveitis had been refractory to previous topical and systemic corticosteroids, methotrexate (MTX), and other synthetic and biological disease-modifying antirheumatic drugs, including ≥ 1 tumor necrosis factor-α (TNF-α) inhibitor. Uveitis inactivity was achieved in 10 patients after a mean of 5.7 months of TCZ treatment (in 3 of them, it recurred during followup) and persisted in the remaining 7 patients. By using TCZ, systemic corticosteroids or immunosuppressives could be spared in 7 patients. Macular edema was present in 5 patients at baseline and improved in all of them under TCZ treatment. Arthritis was active in 11 patients at the initial and in 6 at the final followup visit. TCZ appears to represent a therapeutic option for severe JIA-associated uveitis that has been refractory to MTX and TNF-α inhibitors in selected patients. The present data indicate that inflammatory macular edema responds well to TCZ in patients with JIA-associated uveitis.

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

    PubMed

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

    2018-02-01

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

  7. Periodontal therapy reduces plasma levels of interleukin-6, C-reactive protein, and fibrinogen in patients with severe periodontitis and refractory arterial hypertension.

    PubMed

    Vidal, Fábio; Figueredo, Carlos Marcelo S; Cordovil, Ivan; Fischer, Ricardo G

    2009-05-01

    Recent epidemiologic studies suggest that inflammation is the link between periodontal diseases and cardiovascular complications. This study aimed to evaluate the effects of non-surgical periodontal treatment on plasma levels of inflammatory markers (interleukin [IL]-6, C-reactive protein [CRP], and fibrinogen) in patients with severe periodontitis and refractory arterial hypertension. Twenty-two patients were examined and randomly divided into two groups. The test group was composed of 11 patients (mean age, 48.9 +/- 3.9 years) who received periodontal treatment, whereas the control group had 11 patients (mean age, 49.7 +/- 6.0 years) whose treatment was delayed for 3 months. Demographic and clinical periodontal data were collected, and blood tests were performed to measure the levels of IL-6, CRP, and fibrinogen at baseline and 3 months later. The clinical results showed that the mean percentages of sites with bleeding on probing, probing depth (PD) 4 to 5 mm, PD > or =6 mm, clinical attachment loss (CAL) 4 to 5 mm, and CAL > or =6 mm were significantly reduced in the test group 3 months after periodontal treatment. There were no significant differences between the data at baseline and 3 months in the control group. Periodontal treatment significantly reduced the blood levels of fibrinogen, CRP, and IL-6 in the test group. Non-surgical periodontal therapy was effective in improving periodontal clinical data and in reducing the plasma levels of IL-6, CRP, and fibrinogen in hypertensive patients with severe periodontitis.

  8. 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

  9. 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.

  10. 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.

  11. Different treatment modalities for refractory vaginismus in western Saudi Arabia.

    PubMed

    Fageeh, Wafa M K

    2011-06-01

    Although vaginismus is a common sexual dysfunction in Saudi Arabia, there are limited data concerning the treatment modalities associated with patients with symptoms of vaginismus. This study is aimed to evaluate the presentation and different modalities of management in patients with severe refractory vaginismus in western Saudi Arabia. Successful penetrative sexual intercourse suggesting that common elements of the therapies used were successful. A retrospective study of patients presenting with severe refractory vaginismus treated in Jeddah, Saudi Arabia. The subjects were 15 women with third to fourth degree vaginismus who presented to King Abdulazziz University Hospital between January 1, 2008 and January 1, 2009. The mean age of the participants was 23 years. The mean duration of marriage before seeking medical advice was 12 months. Six patients had undergone conventional therapy successfully. The other six cases, four of which had a previous history of treatment failure, and two who were unresponsive to 4 months of conventional therapy were offered botulinum toxin type A. Five patients who received the Botox therapy had satisfactory intercourse on the same day of the treatment. One patient required a repeat injection after 2 months for recurrent vaginismus. Three of the 15 patients refused the treatment as they were already divorced and had only come in to exclude organic causes for their condition. Vaginismus is an overlooked topic in conservative societies such as Saudi Arabia. For most patients, not knowing who to confide in or where to turn to plays a major role in the under diagnosis of vaginismus. Conventional therapy proved effective in mild and moderate cases, while botulinum toxin has a more rapid effect and was thus more effective in severe cases. © 2011 International Society for Sexual Medicine.

  12. Destruction of Refractory Carbon in Protoplanetary Disks

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

    Anderson, Dana E.; Blake, Geoffrey A.; Bergin, Edwin A.

    The Earth and other rocky bodies in the inner solar system contain significantly less carbon than the primordial materials that seeded their formation. These carbon-poor objects include the parent bodies of primitive meteorites, suggesting that at least one process responsible for solid-phase carbon depletion was active prior to the early stages of planet formation. Potential mechanisms include the erosion of carbonaceous materials by photons or atomic oxygen in the surface layers of the protoplanetary disk. Under photochemically generated favorable conditions, these reactions can deplete the near-surface abundance of carbon grains and polycyclic aromatic hydrocarbons by several orders of magnitude onmore » short timescales relative to the lifetime of the disk out to radii of ∼20–100+ au from the central star depending on the form of refractory carbon present. Due to the reliance of destruction mechanisms on a high influx of photons, the extent of refractory carbon depletion is quite sensitive to the disk’s internal radiation field. Dust transport within the disk is required to affect the composition of the midplane. In our current model of a passive, constant- α disk, where α = 0.01, carbon grains can be turbulently lofted into the destructive surface layers and depleted out to radii of ∼3–10 au for 0.1–1 μ m grains. Smaller grains can be cleared out of the planet-forming region completely. Destruction may be more effective in an actively accreting disk or when considering individual grain trajectories in non-idealized disks.« less

  13. Refractory metal shielding /insulation/ increases operating range of induction furnace

    NASA Technical Reports Server (NTRS)

    Ebihara, B. T.

    1965-01-01

    Thermal radiation shield contains escaping heat from an induction furnace. The shield consists of a sheet of refractory metal foil and a loosely packed mat of refractory metal fibers in a concentric pattern. This shielding technique can be used for high temperature ovens, high temperature fluid lines, and chemical reaction vessels.

  14. Bevacizumab for Refractory Gastrointestinal Bleeding in Rendu-Osler-Weber Disease

    PubMed Central

    Bernardes, Carlos; Santos, Sara; Loureiro, Rafaela; Borges, Verónica; Ramos, Gonçalo

    2018-01-01

    Rendu-Osler-Weber disease, also known as hereditary hemorrhagic telangiectasia, is a rare autosomal dominant disorder which is often characterized by recurrent epistaxis, mucocutaneous and gastrointestinal telangiectasias, and visceral arteriovenous malformations. Patients with gastrointestinal involvement can present with a wide spectrum of severity, which may vary from uncomplicated iron deficiency anemia to continuous and refractory bleeding. We present the case of a 62-year-old female, who was admitted with anemia following several episodes of melena, and whose endoscopic examination revealed multiple angiodysplasias in the stomach and small bowel. Despite endoscopic and medical treatment attempts with hormonal agents and octreotide, she developed persistent hemorrhage and severe anemia, requiring frequent red blood cell transfusions. Immediately after initiating bevacizumab (7.5 mg/kg, every 3 weeks), complete cessation of bleeding episodes was observed. Currently, after 1 year of follow-up, she maintained sustained remission without the occurrence of adverse events. PMID:29662934

  15. 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.

  16. Alkali metal-refractory metal biphase electrode for AMTEC

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

  17. 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.

  18. Alloy design for intrinsically ductile refractory high-entropy alloys

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

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

  19. 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

  20. 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.

  1. Biomarker discovery for disease status and symptom severity in children with autism.

    PubMed

    Oztan, Ozge; Jackson, Lisa P; Libove, Robin A; Sumiyoshi, Raena D; Phillips, Jennifer M; Garner, Joseph P; Hardan, Antonio Y; Parker, Karen J

    2018-03-01

    Autism spectrum disorder (ASD) is characterized by social impairments and repetitive behaviors, and affects 1 in 68 US children. Despite ASD's societal impact, its disease mechanisms remain poorly understood. Recent preclinical ASD biomarker discovery research has implicated the neuropeptides oxytocin (OXT) and arginine vasopressin (AVP), and their receptors, OXTR and AVPR1A, in animal models. Efforts to translate these findings to individuals with ASD have typically involved evaluating single neuropeptide measures as biomarkers of ASD and/or behavioral functioning. Given that ASD is a heterogeneous disorder, and unidimensional ASD biomarker studies have been challenging to reproduce, here we employed a multidimensional neuropeptide biomarker analysis to more powerfully interrogate disease status and symptom severity in a well characterized child cohort comprised of ASD patients and neurotypical controls. These blood-based neuropeptide measures, considered as a whole, correctly predicted disease status for 57 out of 68 (i.e., 84%) participants. Further analysis revealed that a composite measure of OXTR and AVPR1A gene expression was the key driver of group classification, and that children with ASD had lower neuropeptide receptor mRNA levels compared to controls. Lower neuropeptide receptor mRNA levels also predicted greater symptom severity for core ASD features (i.e., social impairments and stereotyped behaviors), but were unrelated to intellectual impairment, an associated feature of ASD. Findings from this research highlight the value of assessing multiple related biological measures, and their relative contributions, in the same study, and suggest that low blood neuropeptide receptor availability may be a promising biomarker of disease presence and symptom severity in ASD. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. NETL- Severe Environment Corrosion Erosion Facility

    ScienceCinema

    None

    2018-01-16

    NETL's Severe Environment Corrosion Erosion Facility in Albany studies how new and old materials will stand up to new operating conditions. Work done in the lab supports NETL's oxy-fuel combustion oxidation work, refractory materials stability work, and the fuels program, in particular the hydrogen membrane materials stability work, to determine how best to upgrade existing power plants.

  3. Anthropometric Indices in Children With Refractory Epilepsy.

    PubMed

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

    2016-01-01

    We aimed to assess the effect of body mass index (BMI) on reducing the risk of refractory seizure due to lipoid tissue factors. This matched case-control study, consisted of cases (Patients with refractory epilepsy) and controls (Healthy children) referred to 17 Shahrivar Hospital, Guilan University of Medical Sciences, Guilan, Iran during 2013-2014. Data were gathered by a form including demographic characteristics, type of epilepsy, predominant time of epilepsy, therapeutic approach, frequency of epilepsy, time of disease onset and anthropometric indices. We measured anthropometric indices and transformed them into Z-scores. Data were reported by descriptive statistics (mean and standard deviation) and analyzed by Pearson correlation coefficient, paired t test and multinomial regression analysis test using SPSS 19. There was no significant difference between sex groups regarding anthropometric indices. Generalized and focal types of epilepsies were noted on 57.5% and 38.75% of patients, respectively. Daytime epilepsies happened in 46.25% of patients and 33.75% noted no predominant time for epilepsies. Clinicians indicated poly-therapy for the majority of patients (92.5%). The most common onset times for epilepsies were 36-72 months for 32.5% of patients. Lower onset time indicated lower frequency of refractory epilepsies. Although, there was significant difference between Zheight and predominant time of epilepsies but no significant relation was found between types of epilepsies and frequency of epilepsies with anthropometric indices. Using multivariate regression analysis by backward LR, Zweight and birth weight were noted as the predicting factors of refractory epilepsies. This effect may be because of leptin. Therefore, researchers recommend further investigations regarding this issue in children with epilepsy.

  4. 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.

  5. PROCESS OF PRODUCING REFRACTORY URANIUM OXIDE ARTICLES

    DOEpatents

    Hamilton, N.E.

    1957-12-01

    A method is presented for fabricating uranium oxide into a shaped refractory article by introducing a uranium halide fluxing reagent into the uranium oxide, and then mixing and compressing the materials into a shaped composite mass. The shaped mass of uranium oxide and uranium halide is then fired at an elevated temperature so as to form a refractory sintered article. It was found in the present invention that the introduction of a uraninm halide fluxing agent afforded a fluxing action with the uranium oxide particles and that excellent cohesion between these oxide particles was obtained. Approximately 90% of uranium dioxide and 10% of uranium tetrafluoride represent a preferred composition.

  6. 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.

  7. 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.

  8. Anti-Interleukin-6 Receptor Tocilizumab for Severe Juvenile Idiopathic Arthritis-Associated Uveitis Refractory to Anti-Tumor Necrosis Factor Therapy: A Multicenter Study of Twenty-Five Patients.

    PubMed

    Calvo-Río, Vanesa; Santos-Gómez, Montserrat; Calvo, Inmaculada; González-Fernández, M Isabel; López-Montesinos, Berta; Mesquida, Marina; Adán, Alfredo; Hernández, María Victoria; Maíz, Olga; Atanes, Antonio; Bravo, Beatriz; Modesto, Consuelo; Díaz-Cordovés, Gisela; Palmou-Fontana, Natalia; Loricera, Javier; González-Vela, M C; Demetrio-Pablo, Rosalía; Hernández, J L; González-Gay, Miguel A; Blanco, Ricardo

    2017-03-01

    To assess the efficacy of tocilizumab (TCZ) for the treatment of juvenile idiopathic arthritis (JIA)-associated uveitis. We conducted a multicenter study of patients with JIA-associated uveitis that was refractory to conventional immunosuppressive drugs and anti-tumor necrosis factor (anti-TNF) agents. We assessed 25 patients (21 female; 47 affected eyes) with a mean ± SD age of 18.5 ± 8.3 years. Uveitis was bilateral in 22 patients. Cystoid macular edema was present in 9 patients. Ocular sequelae found at initiation of TCZ included cataracts (n = 13), glaucoma (n = 7), synechiae (n = 10), band keratopathy (n = 12), maculopathy (n = 9), and amblyopia (n = 5). Before TCZ, patients had received corticosteroids, conventional immunosuppressive drugs, and biologic agents (median 2 [range 1-5]), including adalimumab (n = 24), etanercept (n = 8), infliximab (n = 7), abatacept (n = 6), rituximab (n = 2), anakinra (n = 1), and golimumab (n = 1). Patients received 8 mg/kg TCZ intravenously every 4 weeks in most cases. TCZ yielded rapid and maintained improvement in all ocular parameters. After 6 months of therapy, 79.2% of patients showed improvement in anterior chamber cell numbers, and 88.2% showed improvement after 1 year. Central macular thickness measured by optical coherence tomography in patients with cystoid macular edema decreased from a mean ± SD of 401.7 ± 86.8 μm to 259.1 ± 39.5 μm after 6 months of TCZ (P = 0.012). The best-corrected visual acuity increased from 0.56 ± 0.35 to 0.64 ± 0.32 (P < 0.01). After a median follow-up of 12 months, visual improvement persisted, and complete remission of uveitis was observed in 19 of 25 patients. Significant reduction in the prednisone dosage was also achieved. The main adverse effects were severe autoimmune thrombocytopenia in 1 patient, pneumonia and then autoimmune anemia and thrombocytopenia in 1 patient, and viral

  9. Management of patients with refractory angina: Canadian Cardiovascular Society/Canadian Pain Society joint guidelines.

    PubMed

    McGillion, Michael; Arthur, Heather M; Cook, Allison; Carroll, Sandra L; Victor, J Charles; L'allier, Philippe L; Jolicoeur, E Marc; Svorkdal, Nelson; Niznick, Joel; Teoh, Kevin; Cosman, Tammy; Sessle, Barry; Watt-Watson, Judy; Clark, Alexander; Taenzer, Paul; Coyte, Peter; Malysh, Louise; Galte, Carol; Stone, James

    2012-01-01

    Refractory angina (RFA) is a debilitating disease characterized by cardiac pain resistant to conventional treatments for coronary artery disease including nitrates, calcium-channel and β-adrenoceptor blockade, vasculoprotective agents, percutaneous coronary interventions, and coronary artery bypass grafting. The mortality rate of patients living with RFA is not known but is thought to be in the range of approximately 3%. These individuals suffer severely impaired health-related quality of life with recurrent and sustained pain, poor general health status, psychological distress, impaired role functioning, and activity restriction. Effective care for RFA sufferers in Canada is critically underdeveloped. These guidelines are predicated upon a 2009 Canadian Cardiovascular Society (CCS) Position Statement which identified that underlying the problem of RFA management is the lack of a formalized, coordinated, interprofessional strategy between the cardiovascular and pain science/clinical communities. The guidelines are therefore a joint initiative of the CCS and the Canadian Pain Society (CPS) and make practice recommendations about treatment options for RFA that are based on the best available evidence. Concluding summary recommendations are also made, giving direction to future clinical practice and research on RFA management in Canada. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  10. Early prediction of medication refractoriness in children with idiopathic epilepsy based on scalp EEG analysis.

    PubMed

    Lin, Lung-Chang; Ouyang, Chen-Sen; Chiang, Ching-Tai; Yang, Rei-Cheng; Wu, Rong-Ching; Wu, Hui-Chuan

    2014-11-01

    Refractory epilepsy often has deleterious effects on an individual's health and quality of life. Early identification of patients whose seizures are refractory to antiepileptic drugs is important in considering the use of alternative treatments. Although idiopathic epilepsy is regarded as having a significantly lower risk factor of developing refractory epilepsy, still a subset of patients with idiopathic epilepsy might be refractory to medical treatment. In this study, we developed an effective method to predict the refractoriness of idiopathic epilepsy. Sixteen EEG segments from 12 well-controlled patients and 14 EEG segments from 11 refractory patients were analyzed at the time of first EEG recordings before antiepileptic drug treatment. Ten crucial EEG feature descriptors were selected for classification. Three of 10 were related to decorrelation time, and four of 10 were related to relative power of delta/gamma. There were significantly higher values in these seven feature descriptors in the well-controlled group as compared to the refractory group. On the contrary, the remaining three feature descriptors related to spectral edge frequency, kurtosis, and energy of wavelet coefficients demonstrated significantly lower values in the well-controlled group as compared to the refractory group. The analyses yielded a weighted precision rate of 94.2%, and a 93.3% recall rate. Therefore, the developed method is a useful tool in identifying the possibility of developing refractory epilepsy in patients with idiopathic epilepsy.

  11. Productivity costs in patients with refractory chronic rhinosinusitis.

    PubMed

    Rudmik, Luke; Smith, Timothy L; Schlosser, Rodney J; Hwang, Peter H; Mace, Jess C; Soler, Zachary M

    2014-09-01

    Disease-specific reductions in patient productivity can lead to substantial economic losses to society. The purpose of this study was to: 1) define the annual productivity cost for a patient with refractory chronic rhinosinusitis (CRS) and 2) evaluate the relationship between degree of productivity cost and CRS-specific characteristics. Prospective, multi-institutional, observational cohort study. 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 U.S. National Census and the 2013 U.S. Department of Labor statistics. A total of 55 patients with refractory CRS were enrolled. The mean work days lost related to absenteeism and presenteeism were 24.6 and 38.8 days per year, respectively. A total of 21.2 household days were lost per year related to daily sinus care requirements. The overall annual productivity cost was $10,077.07 per patient with refractory CRS. Productivity costs increased with worsening disease-specific QoL (r = 0.440; p = 0.001). Results from this study have demonstrated that the annual productivity cost associated with refractory CRS is $10,077.07 per patient. This substantial cost to society provides a strong incentive to optimize current treatment protocols and continue evaluating novel clinical interventions to reduce this cost. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  12. Productivity Costs in Patients with Refractory Chronic Rhinosinusitis

    PubMed Central

    Rudmik, Luke; Smith, Timothy L.; Schlosser, Rodney J.; Hwang, Peter H.; Mace, Jess C.; Soler, Zachary M.

    2014-01-01

    Objective Disease-specific reductions in patient productivity can lead to substantial economic losses to society. The purpose of this study was to: 1) define the annual productivity cost for a patient with refractory chronic rhinosinusitis (CRS) and 2) evaluate the relationship between degree of productivity cost and CRS-specific characteristics. 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 A total of 55 patients with refractory CRS were enrolled. The mean work days lost related to absenteeism and presenteeism was 24.6 and 38.8 days per year, respectively. A total of 21.2 household days were lost per year related to daily sinus care requirements. The overall annual productivity cost was $10,077.07 per patient with refractory CRS. Productivity costs increased with worsening disease-specific QoL (r=0.440; p=0.001). Conclusion Results from this study have demonstrated that the annual productivity cost associated with refractory CRS is $10,077.07 per patient. This substantial cost to society provides a strong incentive to optimize current treatment protocols and continue evaluating novel clinical interventions to reduce this cost. PMID:24619604

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

    PubMed

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

    2012-01-01

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

  14. 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

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

    PubMed

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

    2013-01-01

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

  16. Launch Pad Flame Trench Refractory Materials

    NASA Technical Reports Server (NTRS)

    Calle, Luz M.; Hintze, Paul E.; Parlier, Christopher R.; Bucherl, Cori; Sampson, Jeffrey W.; Curran, Jerome P.; Kolody, Mark; Perusich, Steve; Whitten, Mary

    2010-01-01

    The launch complexes at NASA's John F. Kennedy Space Center (KSC) are critical support facilities for the successful launch of space-based vehicles. These facilities include a flame trench that bisects the pad at ground level. This trench includes a flame deflector system that consists of an inverted, V-shaped steel structure covered with a high temperature concrete material five inches thick that extends across the center of the flame trench. One side of the "V11 receives and deflects the flames from the orbiter main engines; the opposite side deflects the flames from the solid rocket boosters. There are also two movable deflectors at the top of the trench to provide additional protection to shuttle hardware from the solid rocket booster flames. These facilities are over 40 years old and are experiencing constant deterioration from launch heat/blast effects and environmental exposure. The refractory material currently used in launch pad flame deflectors has become susceptible to failure, resulting in large sections of the material breaking away from the steel base structure and creating high-speed projectiles during launch. These projectiles jeopardize the safety of the launch complex, crew, and vehicle. Post launch inspections have revealed that the number and frequency of repairs, as well as the area and size of the damage, is increasing with the number of launches. The Space Shuttle Program has accepted the extensive ground processing costs for post launch repair of damaged areas and investigations of future launch related failures for the remainder of the program. There currently are no long term solutions available for Constellation Program ground operations to address the poor performance and subsequent failures of the refractory materials. Over the last three years, significant liberation of refractory material in the flame trench and fire bricks along the adjacent trench walls following Space Shuttle launches have resulted in extensive investigations of

  17. Efficacy and safety of biodegradable stents for refractory benign esophageal strictures: the BEST (Biodegradable Esophageal Stent) study.

    PubMed

    Repici, Alessandro; Vleggaar, Frank P; Hassan, Cesare; van Boeckel, Petra G; Romeo, Fabio; Pagano, Nicola; Malesci, Alberto; Siersema, Peter D

    2010-11-01

    Benign esophageal strictures refractory to standard dilation therapy present a challenging problem. Temporary plastic and metal stents have been proposed with inconclusive results. To evaluate the efficacy and safety of a new biodegradable stent for the treatment of refractory benign esophageal strictures (RBESs). Prospective study from 2 European endoscopy centers. Twenty-one patients (11 men/10 women, mean age 60.2 ± 17.6 years) with RBESs defined according to the Kochman criteria treated by placement of a biodegradable stent (Ella stent). Clinical and endoscopic follow-up was scheduled at 1, 2, 3, and 6 months and later only in case of dysphagia recurrence. Pre- and poststenting dysphagia status was graded according to a 5-point scale. Minor and major complication rates were prospectively assessed. Stent insertion was technically successful in all of the patients. At 4 and 7 weeks, stent migration occurred in 2 patients (9.5%). At 3-month endoscopy, the stent appeared to be almost completely fragmented in all remaining patients. The median pre- and poststenting dysphagia scores were 3 (range 3-4) and 1 (range 0-2), respectively (P < .01), with a median follow-up of 53 weeks (range 25-88 weeks). In detail, 9 of 20 patients (45%) were dysphagia free at the end of the follow-up. No major complications occurred. Severe poststenting pain requiring analgesics developed in 3 patients, and minor bleeding was observed in 1 patient. Limited follow-up; nonrandomized study. In this preliminary study, the biodegradable stent showed a favorable risk/benefit ratio, achieving complete relief of dysphagia in nearly 50% of RBES patients without the occurrence of major complications. The use of this stent may be a valuable alternative to repeat endoscopic dilation. Larger studies with longer follow-up are needed. Copyright © 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

  18. Association of Time to Treatment With Short-term Outcomes for Pediatric Patients With Refractory Convulsive Status Epilepticus.

    PubMed

    Gaínza-Lein, Marina; Sánchez Fernández, Iván; Jackson, Michele; Abend, Nicholas S; Arya, Ravindra; Brenton, J Nicholas; Carpenter, Jessica L; Chapman, Kevin E; Gaillard, William D; Glauser, Tracy A; Goldstein, Joshua L; Goodkin, Howard P; Kapur, Kush; Mikati, Mohamad A; Peariso, Katrina; Tasker, Robert C; Tchapyjnikov, Dmitry; Topjian, Alexis A; Wainwright, Mark S; Wilfong, Angus; Williams, Korwyn; Loddenkemper, Tobias

    2018-04-01

    Treatment delay for seizures can lead to longer seizure duration. Whether treatment delay is associated with major adverse outcomes, such as death, remains unknown. To evaluate whether untimely first-line benzodiazepine treatment is associated with unfavorable short-term outcomes. This multicenter, observational, prospective cohort study included 218 pediatric patients admitted between June 1, 2011, and July 7, 2016, into the 11 tertiary hospitals in the United States within the Pediatric Status Epilepticus Research Group. Patients, ranging in age from 1 month to 21 years, with refractory convulsive status epilepticus (RCSE) that did not stop after the administration of at least 2 antiseizure medications were included. Patients were divided into 2 cohorts: those who received the first-line benzodiazepine treatment in less than 10 minutes and those who received it 10 or more minutes after seizure onset (untimely). Data were collected and analyzed from June 1, 2011, to July 7, 2016. The primary outcome was death during the related hospital admission. The secondary outcome was the need for continuous infusion for seizure termination. Multivariate analysis of mortality controlled for structural cause, febrile RCSE, age, and previous neurological history (including previous RCSE events). Use of continuous infusions was additionally adjusted for generalized RCSE, continuous RCSE, and 5 or more administrations of antiseizure medication. A total of 218 patients were included, among whom 116 (53.2%) were male and the median (interquartile range) age was 4.0 (1.2-9.6) years. The RCSE started in the prehospital setting for 139 patients (63.8%). Seventy-four patients (33.9%) received their first-line benzodiazepine treatment in less than 10 minutes, and 144 (66.1%) received untimely first-line benzodiazepine treatment. Multivariate analysis showed that patients who received untimely first-line benzodiazepine treatment had higher odds of death (adjusted odds ratio [AOR], 11

  19. External bioresorbable airway rigidification to treat refractory localized tracheomalacia.

    PubMed

    Gorostidi, François; Reinhard, Antoine; Monnier, Philippe; Sandu, Kishore

    2016-11-01

    Our study evaluates the efficacy of extraluminal bioresorbable plates to treat refractory localized airway malacia in patients undergoing corrective surgery for complex multilevel laryngotracheal stenosis. Retrospective case series. Secondary malacic airway segments were characterized (severity, site, type) by a dynamic transnasal flexible laryngotracheobronchoscopy before surgery. Extraluminal bioresorbable plates were used to stabilize the malacic segment through a transcervical approach under intraoperative flexible endoscopic guidance. Results were evaluated subjectively and by a postoperative dynamic endoscopy. We report our experience in seven patients (6 children, 1 adult). External tracheal stiffening allowed complete or partial resolution of refractory proximal airway malacia in six of seven complex cases described (result in one case is awaited). It allowed quick decannulation in four of seven patients who experienced multiple previous failures. Decannulation failures were due to recurrence of stenosis. With up to 2 years of follow-up, we report no direct complications related to the presence of extraluminal bioresorbable plates around the airway. Extraluminal biodegradable tracheal stiffening represents a valid therapeutic option in select cases of upper airway malacia. It can be highly useful in cases of complex multilevel airway obstructions. External stiffening needs to be planned on a case-to-case basis according to the type of malacia and must be performed under endoscopic guidance. 4. Laryngoscope, 126:2605-2610, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  20. Direct medical costs for partial refractory epilepsy in Mexico.

    PubMed

    García-Contreras, Fernando; Constantino-Casas, Patricia; Castro-Ríos, Angélica; Nevárez-Sida, Armando; Estrada Correa, Gloria del Carmen; Carlos Rivera, Fernando; Guzmán-Caniupan, Jorge; Torres-Arreola, Laura del Pilar; Contreras-Hernández, Iris; Mould-Quevedo, Joaquin; Garduño-Espinosa, Juan

    2006-04-01

    The aim was to determine the direct medical costs in patients with partial refractory epilepsy at the Mexican Institute of Social Security (IMSS) in Mexico. We carried out a multicenter, retrospective-cohort partial-economic evaluation study of partial refractory epilepsy (PRE) diagnosed patients and analyzed patient files from four secondary- and tertiary-level hospitals. PRE patients >12 years of age with two or more antiepileptic drugs and follow-up for at least 1 year were included. The perspective was institutional (IMSS). Only direct healthcare costs were considered, and the timeline was 1 year. Cost techniques were microcosting, average per-service cost, and per-day cost, all costs expressed in U.S. dollars (USD, 2004). We reviewed 813 files of PRE patients: 133 had a correct diagnosis, and only 72 met study inclusion criteria. Fifty eight percent were females, 64% were <35 years of age, 47% were students, in 73% maximum academic level achieved was high school, and 53% were single. Fifty one percent of cases experienced simple partial seizures and 94% had more than one monthly seizure. Annual healthcare cost of the 72 patients was 190,486 USD, ambulatory healthcare contributing 76% and hospital healthcare with 24%. Annual mean healthcare cost per PRE patient was 2,646 USD; time of disease evolution and severity of the patient's illness did not affect costs significantly.

  1. Microwave Measurement of Refractory Materials at High-Temperature

    NASA Astrophysics Data System (ADS)

    Kharkovsky, S.; Zoughi, R.; Smith, J.; Davis, B.; Limmer, R.

    2009-03-01

    Knowledge of the electrical behavior of refractory materials may enable the development and optimization of microwave nondestructive techniques to detect and evaluate changes in their physical properties while the materials are in service. This paper presents the results of a limited and preliminary investigation in which two refractory materials (dense chrome and dense zircon) were subjected to increasing temperature in a furnace and in which a frequency-modulated continuous-wave radar operating in the frequency range of 8-18 GHz radar was used to evaluate their attenuation properties.

  2. Maternal Custody Status and Living Arrangements of Children of Women with Severe Mental Illness

    ERIC Educational Resources Information Center

    Sands, Roberta G.; Koppelman, Nancy; Solomon, Phyllis

    2004-01-01

    The authors report results of a pilot study on the custody status of 20 women with severe mental illnesses who were parents of a total of 76 children. The mothers had some of their children living with them and others dispersed among kinship and nonkinship arrangements. Qualitative findings illustrate how bewildered these women were about the…

  3. 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.

  4. Refractory and Resistant Hypertension: Antihypertensive Treatment Failure versus Treatment Resistance

    PubMed Central

    2016-01-01

    Resistant hypertension has for many decades been defined as difficult-to-treat hypertension in order to identify patients who may benefit from special diagnostic and/or therapeutic considerations. Recently, the term "refractory hypertension" has been proposed as a novel phenotype of antihypertensive failure, that is, patients whose blood pressure cannot be controlled with maximal treatment. Early studies of this phenotype indicate that it is uncommon, affecting less than 5% of patients with resistant hypertension. Risk factors for refractory hypertension include obesity, diabetes, chronic kidney disease, and especially, being of African origin. Patients with refractory are at high cardiovascular risk based on increased rates of known heart disease, prior stroke, and prior episodes of congestive heart failure. Mechanisms of refractory hypertension need exploration, but early studies suggest a possible role of heightened sympathetic tone as evidenced by increased office and ambulatory heart rates and higher urinary excretion of norepinephrine compared to patients with controlled resistant hypertension. Important negative findings argue against refractory hypertension being fluid dependent as is typical of resistant hypertension, including aldosterone levels, dietary sodium intake, and brain natriuretic peptide levels being similar or even less than patients with resistant hypertension and the failure to control blood pressure with use of intensive diuretic therapy, including both a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Further studies, especially longitudinal assessments, are needed to better characterize this extreme phenotype in terms of risk factors and outcomes and hopefully to identify effective treatment strategies. PMID:27721847

  5. Treatment of Refractory Idiopathic Supraorbital Neuralgia Using Percutaneous Pulsed Radiofrequency.

    PubMed

    Luo, Fang; Lu, Jingjing; Ji, Nan

    2018-02-26

    No ideal therapeutic method currently exists for refractory idiopathic supraorbital neuralgia patients who do not respond to conservative therapy, including medications and nerve blocks. Pulsed radiofrequency is a neuromodulation technique that does not produce sequelae of nerve damage after treatment. However, the efficacy of percutaneous pulsed radiofrequency for the treatment of refractory idiopathic supraorbital neuralgia is still not clear. The purpose of our study was to evaluate the efficacy and safety of pulsed radiofrequency treatment of the supraorbital nerve for refractory supraorbital neuralgia patients. We prospectively investigated the long-term effects of ultrasound-guided percutaneous pulsed radiofrequency in the treatment of 22 refractory idiopathic supraorbital neuralgia patients. A reduction in the verbal pain numeric rating scale score of more than 50% was used as the standard of effectiveness. The effectiveness rates at different time points within 2 years were calculated. After a single pulsed radiofrequency treatment, the effectiveness rate at 1 and 3 months was 77%, and the rates at 6 months, 1 year, and 2 years were 73%, 64%, and 50%, respectively. Except for a small portion of patients (23%) who experienced mild upper eyelid ecchymosis that gradually disappeared after approximately 2 weeks, no obvious complications were observed. In conclusion, the results of our study demonstrate that for patients with refractory idiopathic supraorbital neuralgia, percutaneous pulsed radiofrequency may be an effective and safe treatment choice. © 2018 World Institute of Pain.

  6. 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

  7. Surgical interventions in patients with chronic constipation refractory to intensive medical treatment.

    PubMed

    Yalcin, Samet; Yalcin, Bulent; Gecim, Ethem I

    2009-01-01

    Management of patients with chronic constipation (CC), irresponsive to medical treatment, is very difficult. There are some surgical approaches reported for the treatment. In this study we aimed to assess the results of different surgical procedures in patients with severe CC who were refractory to intensive medical treatments. Fifteen patients with refractory chronic constipation underwent surgical management between 1998 and 2003 in Ankara University School of Medicine Department of General Surgery. Median age of the patients was 40 years (range, 24-77), female/male ratio was 11/4, median duration of symptoms was 13 years (range, 4-35 years) and median interval of two subsequent bowel movements was 15 (range, 5-30) days. Preoperative evaluation including barium enema, colonoscopy, colonic transit time, and cinedefecography and balloon expulsion test were done in all patients. Clinical analysis of constipation with these tests indicated a simple slow transit colon in three patients but more complicated variations of combined anatomical functional disorders in the rest of the cases. Surgical procedures consisted of total colectomy, Frykman-Goldberg procedure, Wells procedure and appendisostomy, laparoscopically in 8 of them. Deep vein thrombosis developed in the postoperative period after rectopexy and pelvic floor repair in one case. The median follow-up time was 5.5 years. Fourteen (93.3%) patients had an excellent bowel movement and were highly satisfied with the surgical management. Surgical interventions may be beneficial in selected patients with refractory chronic constipation (Tab. 2, Ref. 13). Full Text (Free, PDF) www.bmj.sk.

  8. 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.

  9. Refractory coeliac disease in a country with a high prevalence of clinically-diagnosed coeliac disease.

    PubMed

    Ilus, T; Kaukinen, K; Virta, L J; Huhtala, H; Mäki, M; Kurppa, K; Heikkinen, M; Heikura, M; Hirsi, E; Jantunen, K; Moilanen, V; Nielsen, C; Puhto, M; Pölkki, H; Vihriälä, I; Collin, P

    2014-02-01

    Refractory coeliac disease (RCD) is thought to be a rare disorder, but the accurate prevalence is unknown. We aimed to identify the prevalence of and the risk factors for developing RCD in a Finnish population where the clinical detection rate of coeliac disease is high. The study involved 11 hospital districts in Finland where the number of treated RCD patients (n = 44), clinically diagnosed coeliac disease patients (n = 12 243) and adult inhabitants (n = 1.7 million) was known. Clinical characteristics at diagnosis of coeliac disease between the RCD patients and patients with uncomplicated disease were compared. The prevalence of RCD was 0.31% among diagnosed coeliac disease patients and 0.002% in the general population. Of the enrolled 44 RCD patients, 68% had type I and 23% type II; in 9% the type was undetermined. Comparing 886 patients with uncomplicated coeliac disease with these 44 patients that developed RCD later in life, the latter were significantly older (median 56 vs 44 years, P < 0.001), more often males (41% vs. 24%, P = 0.012) and seronegative (30% vs. 5%, P < 0.001) at the diagnosis of coeliac disease. Patients with evolving RCD had more severe symptoms at the diagnosis of coeliac disease, including weight loss in 36% (vs. 16%, P = 0.001) and diarrhoea in 54% (vs. 38%, P = 0.050). Refractory coeliac disease is very rare in the general population. Patients of male gender, older age, severe symptoms or seronegativity at the diagnosis of coeliac disease are at risk of future refractory coeliac disease and should be followed up carefully. © 2014 John Wiley & Sons Ltd.

  10. Oxidants and anti-oxidants status in acne vulgaris patients with varying severity.

    PubMed

    Al-Shobaili, Hani A

    2014-01-01

    Acne vulgaris is a common dermatological disorder with a multifactorial pathogenesis. Oxidative status has been implicated in the pathogenesis of several skin diseases, including acne. This study was aimed to investigate the levels of oxidative stress biomarkers in acne vulgaris patients with varying severities. The study involved 156 patients with acne and 46 healthy human controls. Based on clinical examination, patients were grouped into 3 subgroups as follows: mild, moderate, and severe acne. Oxidative stress was examined by measuring plasma levels of catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde (MDA). Plasma levels of MDA in acne patients were significantly higher as compared with that of the controls, whereas activities of the antioxidant enzymes SOD and CAT were lower. Moreover, TAC was also low in acne patients as compared with that of the controls. Higher MDA levels in the severe acne subgroup as compared with that of the mild and moderate subgroups were also observed. Furthermore, in the severe acne subgroup, a significant negative correlation was observed between MDA and CAT levels. The data suggests that oxidative stress plays a key role in acne progress and may be employed as a biomarker index to assess the disease's activity and to monitor its treatment.

  11. KIT Inhibition by Imatinib in Patients with Severe Refractory Asthma

    PubMed Central

    Cahill, Katherine N.; Katz, Howard R.; Cui, Jing; Lai, Juying; Kazani, Shamsah; Crosby-Thompson, Allison; Garofalo, Denise; Castro, Mario; Jarjour, Nizar; DiMango, Emily; Erzurum, Serpil; Trevor, Jennifer L.; Shenoy, Kartik; Chinchilli, Vernon M.; Wechsler, Michael E.; Laidlaw, Tanya M.; Boyce, Joshua A.; Israel, Elliot

    2017-01-01

    BACKGROUND Mast cells are present in the airways of patients who have severe asthma despite glucocorticoid treatment; these cells are associated with disease characteristics including poor quality of life and inadequate asthma control. Stem cell factor and its receptor, KIT, are central to mast-cell homeostasis. We conducted a proof-of-principle trial to evaluate the effect of imatinib, a KIT inhibitor, on airway hyper-responsiveness, a physiological marker of severe asthma, as well as on airway mast-cell numbers and activation in patients with severe asthma. METHODS We conducted a randomized, double-blind, placebo-controlled, 24-week trial of imatinib in patients with poorly controlled severe asthma who had airway hyperresponsiveness despite receiving maximal medical therapy. The primary end point was the change in airway hyperresponsiveness, measured as the concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20% (PC20). Patients also underwent bronchoscopy. RESULTS Among the 62 patients who underwent randomization, imatinib treatment reduced airway hyperresponsiveness to a greater extent than did placebo. At 6 months, the methacholine PC20 increased by a mean (±SD) of 1.73±0.60 doubling doses in the imatinib group, as compared with 1.07±0.60 doubling doses in the placebo group (P = 0.048). Imatinib also reduced levels of serum tryptase, a marker of mast-cell activation, to a greater extent than did placebo (decrease of 2.02±2.32 vs. 0.56±1.39 ng per milliliter, P = 0.02). Airway mast-cell counts declined in both groups. Muscle cramps and hypophosphatemia were more common in the imatinib group than in the placebo group. CONCLUSIONS In patients with severe asthma, imatinib decreased airway hyperresponsiveness, mast-cell counts, and tryptase release. These results suggest that KIT-dependent processes and mast cells contribute to the pathobiologic basis of severe asthma. (Funded by the National Institutes of Health and

  12. 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.

  13. 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

  14. 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.

  15. [Assessing nutritional status of severe malnutrition patients by bioelectrical impedance technique: a multicenter prospective study].

    PubMed

    Li, Qiang; Li, Xueni; Leng, Yuxin; Zhu, Xi; Yao, Gaiqi

    2018-02-01

    To assess the nutritional status of severe malnutrition patients with anorexia nervosa by multi-frequency bioelectrical impedance technique, and to provide the basis for nutritional support therapy. A prospective study was conducted. Twenty-six severe malnutrition patients with anorexia nervosa, body mass index (BMI) ≤ 16 kg/m 2 admitted to intensive care unit (ICU) of Peking University Third Hospital and general three ward of Peking University Sixth Hospital from June 1st to September 30th, 2017 were enrolled. The extracellular water (ECW), intracellular water (ICW), ECW/ICW ratio, adipose tissue mass (ATM), lean tissue mass (LTM), total body water/body weight (TBW/WT), ATM/WT, and LTM/WT were measured by multi-frequency bioelectrical impedance meter. Thirty-eighty healthy volunteers with normal nutritional status (23.0 kg/m 2 > BMI > 18.5 kg/m 2 ) matched by gender and height were enrolled as healthy control group. The predictive value of main body composition for nutritional status were analyzed by receiver operating characteristic (ROC) curve. All the patients were female. There was no significant difference in height between two groups, but WT and BMI in the severe malnutrition group were significantly higher than those in the healthy control group [WT (kg): 38.1±4.9 vs. 54.2±3.3, BMI (kg/m 2 ): 13.6±2.5 vs. 21.2±1.1, both P < 0.01]. Compared with the healthy control group, the ECW, ICW, ATM, LTM, ATM/WT and LTM/WT were significantly decreased in the severe malnutrition group [ECW (L): 9.02±0.42 vs. 10.19±0.77, ICW (L): 12.6±0.9 vs.19.1±1.3, ATM (kg): 9.3±1.1 vs. 16.6±1.9, LTM (kg): 16.5±1.5 vs. 26.1±1.7, ATM/WT: 0.26±0.02 vs. 0.30±0.02, LTM/WT: 0.22±0.02 vs. 0.26±0.01, all P < 0.01], the ECW/ICW and TBW/WT were significantly increased in the severe malnutrition group (ECW/ICW: 0.72±0.06 vs. 0.54±0.06, TBW/WT: 0.58±0.02 vs. 0.52±0.02, both P < 0.01). It was shown by ROC curve analysis that the area under ROC curve (AUC) of TBW/WT, ATM

  16. 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.

  17. Method of nitriding refractory metal articles

    DOEpatents

    Tiegs, Terry N.; Holcombe, Cressie E.; Dykes, Norman L.; Omatete, Ogbemi O.; Young, Albert C.

    1994-01-01

    A method of nitriding a refractory-nitride forming metal or metalloid articles and composite articles. A consolidated metal or metalloid article or composite is placed inside a microwave oven and nitrogen containing gas is introduced into the microwave oven. The metal or metalloid article or composite is heated to a temperature sufficient to react the metal or metalloid with the nitrogen by applying a microwave energy within the microwave oven. The metal or metalloid article or composite is maintained at that temperature for a period of time sufficient to convert the article of metal or metalloid or composite to an article or composite of refractory nitride. In addition, a method of applying a coating, such as a coating of an oxide, a carbide, or a carbo-nitride, to an article of metal or metalloid by microwave heating.

  18. Method of nitriding refractory metal articles

    DOEpatents

    Tiegs, T.N.; Holcombe, C.E.; Dykes, N.L.; Omatete, O.O.; Young, A.C.

    1994-03-15

    A method of nitriding a refractory-nitride forming metal or metalloid articles and composite articles. A consolidated metal or metalloid article or composite is placed inside a microwave oven and nitrogen containing gas is introduced into the microwave oven. The metal or metalloid article or composite is heated to a temperature sufficient to react the metal or metalloid with the nitrogen by applying a microwave energy within the microwave oven. The metal or metalloid article or composite is maintained at that temperature for a period of time sufficient to convert the article of metal or metalloid or composite to an article or composite of refractory nitride. In addition, a method of applying a coating, such as a coating of an oxide, a carbide, or a carbo-nitride, to an article of metal or metalloid by microwave heating.

  19. Barrier Coatings for Refractory Metals and Superalloys

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

    SM Sabol; BT Randall; JD Edington

    2006-02-23

    In the closed working fluid loop of the proposed Prometheus space nuclear power plant (SNPP), there is the potential for reaction of core and plant structural materials with gas phase impurities and gas phase transport of interstitial elements between superalloy and refractory metal alloy components during service. Primary concerns are surface oxidation, interstitial embrittlement of refractory metals and decarburization of superalloys. In parallel with kinetic investigations, this letter evaluates the ability of potential coatings to prevent or impede communication between reactor and plant components. Key coating requirements are identified and current technology coating materials are reviewed relative to these requirements.more » Candidate coatings are identified for future evaluation based on current knowledge of design parameters and anticipated environment. Coatings were identified for superalloys and refractory metals to provide diffusion barriers to interstitial transport and act as reactive barriers to potential oxidation. Due to their high stability at low oxygen potential, alumina formers are most promising for oxidation protection given the anticipated coolant gas chemistry. A sublayer of iridium is recommended to provide inherent diffusion resistance to interstitials. Based on specific base metal selection, a thin film substrate--coating interdiffusion barrier layer may be necessary to meet mission life.« less

  20. 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.

  1. Simulation of meso-damage of refractory based on cohesion model and molecular dynamics method

    NASA Astrophysics Data System (ADS)

    Zhao, Jiuling; Shang, Hehao; Zhu, Zhaojun; Zhang, Guoxing; Duan, Leiguang; Sun, Xinya

    2018-06-01

    In order to describe the meso-damage of the refractories more accurately, and to study of the relationship between the mesostructured of the refractories and the macro-mechanics, this paper takes the magnesia-carbon refractories as the research object and uses the molecular dynamics method to instead the traditional sequential algorithm to establish the meso-particles filling model including small and large particles. Finally, the finite element software-ABAQUS is used to conducts numerical simulation on the meso-damage evolution process of refractory materials. From the results, the process of initiation and propagation of microscopic interface cracks can be observed intuitively, and the macroscopic stress-strain curve of the refractory material is obtained. The results show that the combination of molecular dynamics modeling and the use of Python in the interface to insert the cohesive element numerical simulation, obtaining of more accurate interface parameters through parameter inversion, can be more accurate to observe the interface of the meso-damage evolution process and effective to consider the effect of the mesostructured of the refractory material on its macroscopic mechanical properties.

  2. Highly Refractory Porous Ceramics,

    DTIC Science & Technology

    1979-03-14

    some cases is not desirable. A uniform distribution of tem- peratures in the melting ch the use of thermally insulating materials, i. e. stability of...materials with micropores that a are inaccessible to penetration by sl s and other melts , which appears, how- ever, to be a very difficult problem...requirements for refractoriness, chemical stability, etc. In accordance with GOST 5040-68, maximum temperatures were established for the melting chamber

  3. 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

  4. 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

  5. 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

  6. Tioguanine in the treatment of refractory coeliac disease--a single centre experience.

    PubMed

    Tack, G J; van Asseldonk, D P; van Wanrooij, R L J; van Bodegraven, A A; Mulder, C J

    2012-08-01

    Refractory coeliac disease type I is a complicated form of coeliac disease characterised by primary or secondary resistance to a gluten-free diet with persisting or reoccurring intestinal villous atrophy and symptoms of malabsorption. Besides corticosteroids, azathioprine has been advocated for the treatment of refractory coeliac disease type I. However, tioguanine (TG) might be better tolerated and more efficacious owing to a simpler metabolism towards bioactivation. To evaluate tolerability and effectiveness of the nonconventional thiopurine derivative TG in refractory coeliac disease type I. Refractory coeliac disease type I patients treated with TG between June 2001 and November 2010 with a follow-up period of at least 1 year were included. Adverse events, laboratory values, 6-thioguanine nucleotide concentrations and rates of both clinical and histological response were evaluated at baseline and during follow-up. Twelve adult refractory coeliac disease type I patients were included. The median TG treatment duration was 14 months. Ten patients tolerated TG treatment on the long term, whereas two patients withdrew treatment due to adverse events. No nodular regenerative hyperplasia of the liver was observed. During follow-up clinical and histological response was observed in 83% and 78%, respectively. Corticosteroid dependency decreased by 50%. Tioguanine appears to be a convenient drug for the treatment of refractory coeliac disease type I based on higher histological and similar clinical response rates as compared with historical conventional therapies. © 2012 Blackwell Publishing Ltd.

  7. A polymorphism in the glucocorticoid receptor gene is associated with refractory hypotension in premature infants.

    PubMed

    Ogasawara, Kei; Sato, Maki; Hashimoto, Koichi; Imamura, Takashi; Go, Hayato; Hosoya, Mitsuaki

    2018-06-01

    Glucocorticoids play an important role in endocrine control. The association of glucocorticoid receptor (GR) gene polymorphisms with altered sensitivity to glucocorticoid therapy has been reported in adults. However, there are few such reports in infants. The present study analyzed the prevalence of four GR polymorphisms in preterm infants born before 30 weeks of gestation and determined the associations between these polymorphisms and clinical outcomes in the infants. Totally, 41 preterm infants born at two hospitals in Fukushima were retrospectively screened for the presence of four GR gene polymorphisms, using a TaqMan single-nucleotide polymorphism genotyping assay. The effect of GR gene polymorphisms on clinical outcomes during hospitalization was evaluated. The following primary clinical outcomes were assessed: refractory hypotension in the acute phase and/or severe bronchopulmonary dysplasia, maximum dopamine and dobutamine doses administered, and total hydrocortisone dose administered in the first 48 h of life. Multivariate analysis with logistic regression was used to assess the association between clinical factors and refractory hypotension. Of the four GR polymorphisms, only the BclI polymorphism was detected. The genotype distribution was as follows: C/C, 33; C/G, 8; and G/G, 0 infants. Significant differences were observed between the C/C and C/G genotypes with respect to the following variables: refractory hypotension (6% vs. 50%), dopamine dose [3.0 (2.0-4.0) vs. 4.8 (4.0-7.5) μg/kg/min], dobutamine dose [2.4 (0.0-3.6) vs. 4.0 (0-10.0) μg/kg/min], and total hydrocortisone dose administered in the first 48 h of life [2.0 (0-10.0) vs. 6.0 (0-12.0) mg/kg]. Multivariate analysis showed that the BclI genotype (C/C) was significantly less associated with refractory hypotension in the acute phase (odds ratio, 0.008; 95% confidence interval, 0.000-0.371; p = 0.013). The incidence of refractory hypotension in infants with the C/C genotype was initially

  8. 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.

  9. 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.

  10. Pre-fired, refractory block slag dams for wet bottom furnace floors

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

    Vihnicka, R.S.; Meskimen, R.L.

    1998-12-31

    Slagging (wet bottom), utility boilers count on a refractory coating over the furnace floor tube structure for protection from corrosion damage from both the harsh, hot gas atmosphere from the burning fuel and the acidic coal slag. To protect and extend the life of this protective refractory coating the boiler original equipment manufacturers (OEMs) utilized a water-cooled monkey ring or slag chill ring (typically a 6--8 inch high ring of small diameter tubes) surrounding the slag tap locations on most wet bottom furnace floors (both utility and package boilers). The old water-cooled tube ring was such a high maintenance item,more » however, that it`s use has been discontinued in all but the most extreme environments throughout both utility and industrial applications. Where the use of the ring was discontinued, there has been a corresponding shortening of life on the protective floor refractory coatings (high maintenance cost), further aggravated by recent OSHA restrictions limiting the use of chrome oxide refractory materials in these types of boilers. This paper describes the developmental process and the final resultant product (a non-watercooled, slag dam made from pre-fired refractory shapes), undertaken by the inventors. Derived operational benefits a concept 2 project, with NO{sub x} Title 4 and Title 1 significance (which is currently underway) will also be detailed.« less

  11. 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

  12. 40 CFR 471.50 - Applicability; description of the refractory metals forming subcategory.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... refractory metals forming subcategory. 471.50 Section 471.50 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS NONFERROUS METALS FORMING AND METAL POWDERS POINT SOURCE CATEGORY Refractory Metals Forming Subcategory § 471.50 Applicability; description of the...

  13. Compatibility of refractory materials for nuclear reactor poison control systems

    NASA Technical Reports Server (NTRS)

    Sinclair, J. H.

    1974-01-01

    Metal-clad poison rods have been considered for the control system of an advanced space power reactor concept studied at the NASA Lewis Research Center. Such control rods may be required to operate at temperatures of about 140O C. Selected poison materials (including boron carbide and the diborides of zirconium, hafnium, and tantalum) were subjected to 1000-hour screening tests in contact with candidate refractory metal cladding materials (including tungsten and alloys of tantalum, niobium, and molybdenum) to assess the compatibility of these materials combinations at the temperatures of interest. Zirconium and hafnium diborides were compatible with refractory metals at 1400 C, but boron carbide and tantalum diboride reacted with the refractory metals at this temperature. Zirconium diboride also showed promise as a reaction barrier between boron carbide and tungsten.

  14. Accelerating drug development in pediatric cancer: a novel Phase I study design of venetoclax in relapsed/refractory malignancies.

    PubMed

    Place, Andrew E; Goldsmith, Kelly; Bourquin, Jean-Pierre; Loh, Mignon L; Gore, Lia; Morgenstern, Daniel A; Sanzgiri, Yeshwant; Hoffman, David; Zhou, Ying; Ross, Jeremy A; Prine, Betty; Shebley, Mohamad; McNamee, Megan; Farazi, Thalia; Kim, Su Young; Verdugo, Maria; Lash-Fleming, Leanne; Zwaan, C Michel; Vormoor, Josef

    2018-03-29

    Venetoclax is a highly selective, potent BCL-2 inhibitor that is approved for some patients previously treated for chronic lymphocytic leukemia, and has shown promising activity in adult studies across several hematologic malignancies. Preclinical studies have demonstrated venetoclax activity in pediatric patient-derived xenograft models and cell lines; however, clinical studies in pediatric patients have yet to be conducted. The prognosis is poor for children with most relapsed/refractory malignancies, and limited treatment options result in unmet clinical need. Herein, we describe the rationale and design of the first study of venetoclax in pediatric patients with relapsed/refractory malignancies: a Phase I trial investigating the safety and pharmacokinetics of venetoclax monotherapy followed by the addition of chemotherapy (Trial registration: EudraCT 2017-000439-14; NCT03236857).

  15. 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.

  16. A review of recombinant factor VII for refractory bleeding in nonhemophilic trauma patients.

    PubMed

    Barletta, Jeffrey F; Ahrens, Christine L; Tyburski, James G; Wilson, Robert F

    2005-03-01

    Recombinant factor VII (rFVII) is an attractive agent to control refractory, coagulopathic bleeding in patients following major surgery. The purpose of this review is to evaluate the published experiences of rFVII in adult, nonhemophilic, surgical and trauma patients. A computerized literature search was conducted to identify articles pertaining to rFVII use for refractory bleeding in adult, nonhemophilic, surgical patients. The selected articles were reviewed and the applicable data was analyzed. A total of 117 patients were found in 8 case series and 24 case reports. Overall, rFVII was effective in restoring hemostasis in 99/117 (85%) patients with 76/99 (77%) surviving to hospital discharge. In trauma patients, hemostasis was achieved in 20/26 (77%) patients and 17/20 (85%) survived. There were 5 (4%) thromboembolic events observed in the 117 cases and much disparity was noted with the initial dose. Severe acidosis affected the activity of rFVII. Recombinant factor VII is an effective therapeutic agent for achieving hemostasis in nonhemophilic surgical patients. Published clinical experiences, however, are limited to small case series and case reports.

  17. [Rational combinations of antiepileptic drugs for refractory epilepsy].

    PubMed

    Yoshino, Aihide

    2011-04-01

    Although epilepsy surgery is most effective for patients with intractable epilepsy, a majority of them is not eligible for the surgery. Most of patients with refractory epilepsy are eventually treated with polypharmacy in hope of seizure control. Therefore, rational combinations of antiepileptic drugs are needed to control intractable seizures. Drug combinations should be rationally chosen based on the evidence of synergic efficacy and on avoidance of neurotoxicity. Several clinical studies suggest that the combination of valproate with lamotrigine has synergic antiepileptic effect. It has also been reported that the combination of carbamazepine with lamotrigine paradoxically decreases efficacy and increases toxicity. Animal studies using isobolography suggest that the combinations of topiramate with lamotrigine or levetiracetam are also promising on both seizure control and neurotoxicity. Clinical research is needed to examine these combinations.

  18. Physical activity, health status and risk of hospitalization in patients with severe chronic obstructive pulmonary disease.

    PubMed

    Benzo, Roberto P; Chang, Chung-Chou H; Farrell, Max H; Kaplan, Robert; Ries, Andrew; Martinez, Fernando J; Wise, Robert; Make, Barry; Sciurba, Frank

    2010-01-01

    Chronic obstructive pulmonary disease (COPD) is a leading cause of death and 70% of the cost of COPD is due to hospitalizations. Self-reported daily physical activity and health status have been reported as predictors of a hospitalization in COPD but are not routinely assessed. We tested the hypothesis that self-reported daily physical activity and health status assessed by a simple question were predictors of a hospitalization in a well-characterized cohort of patients with severe emphysema. Investigators gathered daily physical activity and health status data assessed by a simple question in 597 patients with severe emphysema and tested the association of those patient-reported outcomes to the occurrence of a hospitalization in the following year. Multiple logistic regression analyses were used to determine predictors of hospitalization during the first 12 months after randomization. The two variables tested in the hypothesis were significant predictors of a hospitalization after adjusting for all univariable significant predictors: >2 h of physical activity per week had a protective effect [odds ratio (OR) 0.60; 95% confidence interval (95% CI) 0.41-0.88] and self-reported health status as fair or poor had a deleterious effect (OR 1.57; 95% CI 1.10-2.23). In addition, two other variables became significant in the multivariate model: total lung capacity (every 10% increase) had a protective effect (OR 0.88; 95% CI 0.78-0.99) and self-reported anxiety had a deleterious effect (OR 1.75; 95% CI 1.13-2.70). Self-reported daily physical activity and health status are independently associated with COPD hospitalizations. Our findings, assessed by simple questions, suggest the value of patient-reported outcomes in developing risk assessment tools that are easy to use.

  19. The effect of various sintering temperature on used refractory towards its physical properties

    NASA Astrophysics Data System (ADS)

    Sudibyo; Wulandari, Y. R.; Amin, M.; Azhar

    2018-01-01

    The used magnesia refractory from the kiln of cement industry was successfully recycled to new refractory using Kaolin as an adhesive. In this work, the temperatures of sintering were varied from 1000°C to 1500°C. The result shows that the increment temperature effects in sintering process will enhance refractory physical properties such as bulk density, cold crushing strength or pressure strength and thermal conductivity. Meanwhile, the porosity was decreased as the increase of the sintering temperature.

  20. Adult venovenous extracorporeal membrane oxygenation for severe respiratory failure: Current status and future perspectives.

    PubMed

    Sen, Ayan; Callisen, Hannelisa E; Alwardt, Cory M; Larson, Joel S; Lowell, Amelia A; Libricz, Stacy L; Tarwade, Pritee; Patel, Bhavesh M; Ramakrishna, Harish

    2016-01-01

    Extracorporeal membrane oxygenation (ECMO) for severe acute respiratory failure was proposed more than 40 years ago. Despite the publication of the ARDSNet study and adoption of lung protective ventilation, the mortality for acute respiratory failure due to acute respiratory distress syndrome has continued to remain high. This technology has evolved over the past couple of decades and has been noted to be safe and successful, especially during the worldwide H1N1 influenza pandemic with good survival rates. The primary indications for ECMO in acute respiratory failure include severe refractory hypoxemic and hypercarbic respiratory failure in spite of maximum lung protective ventilatory support. Various triage criteria have been described and published. Contraindications exist when application of ECMO may be futile or technically impossible. Knowledge and appreciation of the circuit, cannulae, and the physiology of gas exchange with ECMO are necessary to ensure lung rest, efficiency of oxygenation, and ventilation as well as troubleshooting problems. Anticoagulation is a major concern with ECMO, and the evidence is evolving with respect to diagnostic testing and use of anticoagulants. Clinical management of the patient includes comprehensive critical care addressing sedation and neurologic issues, ensuring lung recruitment, diuresis, early enteral nutrition, treatment and surveillance of infections, and multisystem organ support. Newer technology that delinks oxygenation and ventilation by extracorporeal carbon dioxide removal may lead to ultra-lung protective ventilation, avoidance of endotracheal intubation in some situations, and ambulatory therapies as a bridge to lung transplantation. Risks, complications, and long-term outcomes and resources need to be considered and weighed in before widespread application. Ethical challenges are a reality and a multidisciplinary approach that should be adopted for every case in consideration.

  1. 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

  2. Impact of Chronic Condition Status and Severity on Dental Utilization for Iowa Medicaid-Enrolled Children

    PubMed Central

    Chi, Donald L.; Momany, Elizabeth T.; Neff, John; Jones, Michael P.; Warren, John J.; Slayton, Rebecca L.; Weber-Gasparoni, Karin; Damiano, Peter C.

    2011-01-01

    Background Although Medicaid-enrolled children with a chronic condition (CC) may be less likely to use dental care because of factors related to their CC, dental utilization for this population is poorly understood. Objective To assess the relationship between CC status and CC severity, respectively, on dental utilization for Iowa Medicaid-enrolled children. Research Design Retrospective cohort study of Iowa Medicaid data (January 1, 2003 to December 31, 2006). Subjects Medicaid-enrolled children aged 3 to 14 (N = 71,115) years. Measures The 3M Corporation Clinical Risk Grouping methods were used to assess CC status (no/yes) and CC severity (episodic/life-long/malignancy/complex). The outcome variable was any dental utilization in 2006. Secondary outcomes included use of diagnostic, preventive, routine restorative, or complex restorative dental care. Results After adjusting for model covariates, Iowa Medicaid-enrolled children with a CC were significantly more likely to use each type of dental care except routine restorative care (P = 0.86) than those without a CC, although the differences in the odds were small (4%–6%). Compared with Medicaid-enrolled children with an episodic CC, children with a life-long CC were less likely to use routine restorative care (P < 0.0001), children with a malignancy were more likely to use complex restorative care (P < 0.03), and children with a complex CC were less likely to use each type of dental care except complex restorative care (P = 0.97). Conclusions There were differences in dental utilization for Iowa Medicaid-enrolled children by CC status and CC severity. Children with complex CCs were the least likely to use dental care. Future research efforts should seek to understand why subgroups of Medicaid-enrolled children with a CC exhibit lower dental utilization. PMID:21150799

  3. Neuromuscular Electrical Stimulation for Treatment-Refractory Chronic Dysphagia in Tube-Fed Patients: A Prospective Case Series.

    PubMed

    Scarponi, Letizia; Mozzanica, Francesco; De Cristofaro, Valeria; Ginocchio, Daniela; Pizzorni, Nicole; Bottero, Alessandro; Schindler, Antonio

    2015-01-01

    The aim of this study was to evaluate the role of neuromuscular electrical stimulation (NMES) in tube-fed patients with severe and chronic dysphagia refractory to traditional swallowing therapy (TT). A total of 11 consecutive dysphagic patients with tube-dependent nutrition and who had not responded to 6 months of TT were enrolled. Each patient received NMES for 30 min and TT for 30 min, twice a day, 5 days per week for 4 weeks. In order to evaluate the swallowing impairment, each patient underwent a fiberoptic endoscopic examination of swallowing immediately before the beginning of the treatment, after 2 weeks and after 4 weeks. All enrolled patients managed to complete the swallowing treatment protocol for at least 2 weeks. After the 4-week treatment, 6 of 11 enrolled patients passed to a total oral diet with single or multiple consistencies despite specific food limitations or special preparation or compensation. Five patients, all affected by the most severe form of dysphagia, maintained tube-dependent nutrition. NMES as adjunctive treatment to TT may offer a new possibility for the management of tube-fed patients who are refractory to TT. © 2016 S. Karger AG, Basel.

  4. Efficacy of combination chemotherapy using irinotecan and nedaplatin for patients with recurrent and refractory endometrial carcinomas: preliminary analysis and literature review.

    PubMed

    Miyamoto, Morikazu; Takano, Masashi; Kuwahara, Mika; Soyama, Hiroaki; Kato, Kento; Matuura, Hiroko; Sakamoto, Takahiro; Takasaki, Kazuki; Aoyama, Tadashi; Yoshikawa, Tomoyuki; Furuya, Kenichi

    2018-01-01

    We aimed to retrospectively evaluate the efficacy and toxicity of an irinotecan hydrochloride (CPT) and nedaplatin (N) combination therapy for recurrent and refractory endometrial carcinoma, administered based on UGT1A1 genotype. Between 2009 and 2017, 21 patients who received CPT-N therapy for recurrent endometrial carcinoma as second- or third-line chemotherapy at our hospital were identified. The CPT-N regimen included 40-70 mg/m 2 of CPT-11 on days 1, 8, and 15, and 50 mg/m 2 of nedaplatin on day 1, q4 weeks. The median patient age was 63 years. The number of prior chemotherapeutic regimens ranged from 1 to 2. Two patients had prior pelvic irradiation. The response rate [ratio of complete remission (CR) to partial remission (PR)] of CPT-N therapy was 3 of 21 (14.3%), and clinical benefit rate (CBR) [the combined percentages of CR, PR, and stable disease (SD)] was 9 of 21 (42.8%). Toxicities included grade 3 neutropenia [4 (19.0%) cases], grade 3 febrile neutropenia [2 (9.5%) cases], and grade 3 diarrhea [3 (14.3%) cases]; all resolved with conservative treatment. Patients with a wild-type UGT1A1 status received higher doses of CPT-11 (p = 0.048) and had similar RR and CBR compared to those with a UGT1A1*6 and *28 status. There were no significant differences in frequencies of hematological or non-hematological toxicities, regardless of UGT1A1 status. The CPT-N regimen for recurrent and refractory endometrial carcinoma had tolerable side effects and significant efficacy. This regimen is a viable treatment option for endometrial carcinoma.

  5. Compatibility Studies of Various Refractory Materials in Contact with Molten Silicon

    NASA Technical Reports Server (NTRS)

    Odonnell, T.; Leipold, M. H.; Hagan, M.

    1978-01-01

    The production of low cost, efficient solar cells for terrestrial electric power generation involves the manipulation of molten silicon with a present need for noncontaminating, high temperature refractories to be used as containment vessels, ribbon-production dies, and dip-coated substrates. Studies were conducted on the wetting behavior and chemical/physical interactions between molten silicon and various refractory materials.

  6. Ascorbic Acid and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Lymphoma

    ClinicalTrials.gov

    2018-03-23

    High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Lymphoma

  7. Five Alzheimer's disease cases with refractory behavioural psychological symptoms of dementia treated with blonanserin.

    PubMed

    Hamuro, Atsushi; Saito, Satona

    2010-12-01

    The aim of the present study was to determine the efficacy, side-effects and tolerability of blonanserin for treating refractory behavioural psychological symptoms of dementia (BPSD). The present study was a 12-week, prospective, structured clinical trial of blonanserin for the treatment of BPSD. The degree of cognitive function, activities of daily living score, and the degree of BPSD were determined using the Mini-Mental State Examination (MMSE), Disability Assessment for Dementia (DAD), Neuropsychiatric Inventory (NPI) and the Rating Scale for Aggressive Behaviour in the Elderly (RAGE). The severity of extrapyramidal symptoms was assessed using the Drug-Induced Extrapyramidal Symptoms scale (DIEEPS). Five patients were enrolled. These patients met the NINCDS-ADRDA criteria. The patients were prescribed more than two kinds of existing antipsychotic drugs and were considered refractory cases; the drugs were discontinued because they were ineffectual and side-effects appeared. Each drug was prescribed independently for at least 2 weeks. The mean changes (at baseline and at the last week, respectively) in the MMSE (12.25, 9.25), in the DAD (6.5, 6.75), in the RAGE (5.5, 5.3) and in the DIEEPS (0.5, 1.5) were minimal. The mean changes in the NPI were two or fewer points. Some side-effects (one gait abnormality and one pneumonia) were observed. The results of this preliminary study show that blonanserin does not have adequate efficacy for the treatment of refractory BPSD. © 2010 The Authors. Psychogeriatrics © 2010 Japanese Psychogeriatric Society.

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

    PubMed Central

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

    2008-01-01

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

  9. Cardiovascular Disease is Associated with COPD Severity and Reduced Functional Status and Quality of Life

    PubMed Central

    Black-Shinn, Jennifer L.; Kinney, Gregory L.; Wise, Anastasia L.; Regan, Elizabeth A.; Make, Barry; Krantz, Mori J.; Barr, R. Graham; Murphy, James R.; Lynch, David; Silverman, Edwin K.; Crapo, James D.; Hokanson, John E.

    2015-01-01

    Introduction Smoking is a major risk factor for both cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD). More individuals with COPD die from CVD than respiratory causes and the risk of developing CVD appears to be independent of smoking burden. Although CVD is a common comorbid condition within COPD, the nature of its relationships to COPD affection status and severity, and functional status is not well understood. Methods The first 2,500 members of the COPDGene cohort were evaluated. Subjects were current and former smokers with a minimum 10 pack year history of cigarette smoking. COPD was defined by spirometry as an FEV1/FVC < lower limit of normal (LLN) with further identification of severity by FEV1 percent of predicted (GOLD stages 2, 3, and 4) for the main analysis. The presence of physician-diagnosed self-reported CVD was determined from a medical history questionnaire administered by a trained staff member. Results A total of 384 (15%) had pre-existing CVD. Self-reported CVD was independently related to COPD (Odds Ratio=1.61, 95% CI=1.18–2.20, p=0.01) after adjustment for covariates with CHF having the greatest association with COPD. Within subjects with COPD, pre-existing self-reported CVD placed subjects at greater risk of hospitalization due to exacerbation, higher BODE index, and greater St. George’s questionnaire score. The presence of self-reported CVD was associated with a shorter six-minute walk distance in those with COPD (p<0.05). Conclusions Self-reported CVD was independently related to COPD with presence of both self-reported CVD and COPD associated with a markedly reduced functional status and reduced quality of life. Identification of CVD in those with COPD is an important consideration in determining functional status. PMID:24831864

  10. Malaria and nutritional status among children with severe acute malnutrition in Niger: a prospective cohort study.

    PubMed

    Oldenburg, Catherine E; Guerin, Philippe J; Berthé, Fatou; Grais, Rebecca F; Isanaka, Sheila

    2018-03-07

    The relationship between malaria infection and nutritional status is complex and previous studies suggest malaria may increase the incidence and severity of malnutrition while malnutrition may increase the risk of malaria infection. Here, we report bi-directional associations between malaria and nutritional status among children with uncomplicated severe acute malnutrition (SAM). The present study is a secondary analysis of a randomized controlled trial for the treatment of uncomplicated SAM in Niger. Children between 6-59 months were enrolled and followed for 12 weeks. Malaria infection was assessed using an HRP2 rapid diagnostic test at admission and at any follow-up visit with fever. We assessed the association of 1) nutritional status at admission on malaria incidence using Cox proportional hazards regression, and 2) malaria infection at admission on nutritional recovery, weight and height gain using linear regression. Of 2,399 children included in the analysis, 1,327 (55.3%) were infected with malaria at admission. Malaria incidence was 12.1 cases per 100 person-months among those without malaria infection at admission. Nutritional status at admission was not associated with malaria incidence. Children with malaria infection at admission, subsequently treated with an artemisinin based combination therapy, had increased weight gain (0.38 g/kg/day, 95% confidence interval [CI] 0.07 to 0.69) and reduced height gain (-0.002 mm/day, 95% CI -0.004 to -0.0008). Malaria infection was common among children treated for uncomplicated SAM. Malaria infection may impair height gain. Proper medical and nutritional management should be assured to prevent adverse effects of malaria infection.

  11. 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

  12. Inhibition of p38 mitogen-activated protein kinase signaling reduces multidrug transporter activity and anti-epileptic drug resistance in refractory epileptic rats.

    PubMed

    Shao, Yiye; Wang, Cuicui; Hong, Zhen; Chen, Yinghui

    2016-03-01

    It is widely recognized that P-glycoprotein (P-gp) mediates drug resistance in refractory epilepsy. However, the molecular mechanism underlying the up-regulation of P-gp expression remains unclear. Our previous studies have demonstrated that p38 mitogen-activated protein kinase (MAPK) regulates P-gp expression in cultured K562 cells. However, a lack of in vivo research leaves unanswered questions regarding whether p38MAPK regulates P-gp expression or drug resistance in refractory epilepsy. This in vivo study examined the effects of p38MAPK on the expression of P-gp and mdr1 in the rat brain and quantified antiepileptic drug (AED) concentrations in the hippocampal extracellular fluid. In addition, the role of p38MAPK in electrical and behavioral activity in a rat epilepsy model was studied. The results indicated that p38MAPK inhibition by SB202190 reduced P-gp expression, while increasing AED concentration in the hippocampal extracellular fluid in refractory epileptic rats. SB202190 also reduced the resistance to AEDs in drug-resistant rats and significantly reduced the severity of seizure activity. These results suggest that p38MAPK could participate in drug resistance in refractory epilepsy through the regulation of P-gp. We show that the specific inhibitor of p38MAPK could down-regulate the expression of multidrug transporter (P-glycoprotein) in blood-brain barrier, increase the concentration of antiepileptic drugs in the hippocampal extracellular fluid and reduce anti-epileptic drug resistance in refractory epileptic rats. We propose that the p38MAPK signaling pathway participates in drug resistance in refractory epilepsy through the regulation of P-glycoprotein expression. © 2015 International Society for Neurochemistry.

  13. Clinical outcomes of intravenous immunoglobulin therapy in refractory uveitis.

    PubMed

    Garcia-Geremias, M; Carreño, E; Epps, S J; Lee, R W J; Dick, A D

    2015-04-01

    Intravenous immunoglobulin (IVIg) therapy has multiple mechanisms of immunomodulatory action. We wished therefore to assess its efficacy in a spectrum of patients with refractory uveitis. Retrospective review of clinical charts was conducted to document response to IVIg treatment in consecutive patients with treatment-refractory uveitis. Main outcome measures were control of intraocular inflammation, visual acuity, progression of the disease, and complications. Four (two male) patients, with a mean age at the beginning of the treatment of 47 years (range: 39-64), were included in the study. Indication for treatment was patients with active non-infectious uveitis refractory to steroids and immunomodulatory therapy. All patients received a course of 0.5 g/kg per day of IVIg for three consecutive days, repeating this course at a mean of 11 week (range: 2-39 weeks) intervals when indicated clinically. The median duration of the IVIg therapy was 7 months (range: 3-14 months). In three patients treatment resulted in stabilisation and prevention of progression of the disease, and additionally in two patients it facilitated a decrease in prednisolone dose. Treatment failed to induce long-term remission in one patient with recurrence of macular oedema. IVIg was well tolerated with neither immediate nor longer-term adverse events observed. In three out of four cases IVIg was an effective adjunctive therapy and well tolerated for the management of treatment-refractory uveitis.

  14. Evolution of Acute Kidney Injury and Its Association With Systemic Hemodynamics in Children With Fluid-Refractory Septic Shock.

    PubMed

    Deep, Akash; Sagar, Hiremath; Goonasekera, Chulananda; Karthikeyan, Palaniswamy; Brierley, Joe; Douiri, Abdel

    2018-07-01

    There are no studies in pediatrics evaluating the progression of acute kidney injury in septic shock. We investigated the evolution of sepsis-associated acute kidney injury and its association with systemic hemodynamics in children with fluid-refractory septic shock. Prospective cohort study. PICU of a tertiary care hospital. All patients with fluid-refractory septic shock (n = 61) between September 2010 and February 2014. Hemodynamic variables using noninvasive ultrasound cardiac output monitor were measured at admission and 6 hourly thereafter till 48 hours. We used the Kidney Disease: Improving Global Outcomes criteria to define and stage acute kidney injury. Associations between various hemodynamic variables and development of acute kidney injury were evaluated. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury and was compared with no acute kidney injury or stage 1 acute kidney injury. Severe acute kidney injury developed in 29.5% (n = 18) of the 61 children with fluid-refractory septic shock, whereas 43 patients (70.49%) had either no or stage 1 acute kidney injury. Most patients who developed acute kidney injury did so within the first 48 hours of PICU admission. Severe acute kidney injury conferred a three-fold increased risk of death by day 28 (hazard ratio, 3.23; 95% CI, 1.52-6.67; p = 0.002), longer ICU stay, and increased duration of mechanical ventilation. Central venous pressure at presentation was higher in severe acute kidney injury by 5 cm H2O. Highest lactate in the first 24 hours of PICU admission, low diastolic blood pressure, low systemic vascular resistance index at admission were associated with severe acute kidney injury. This model reliably predicted stage 2/3 acute kidney injury by day 3 with area under the curve equals to 94%; 95% CI, 88.3-99.99. None of the other hemodynamic variables showed any association with severe acute kidney injury. Manifestations of sepsis-associated acute kidney injury often occur

  15. 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

  16. 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

  17. Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

    PubMed Central

    Wu, Hongyang; Chen, Zhendong; Sun, Guoping; Gu, Kangsheng; Pan, Yueyin; Hao, Jiqing; Du, Yingying; Ning, Jie

    2009-01-01

    Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms. PMID:19267934

  18. Refractory metal particles in refractory inclusions in the Allende meteorite

    NASA Technical Reports Server (NTRS)

    Fuchs, L. H.; Blander, M.

    1980-01-01

    SEM and X-ray analysis were used to study refractory metal particles in five calcium-aluminum-rich inclusions in the Allende meteorite, and a complex variety of compositions and large departures from equilibrium were found. It is suggested that these particles could have been primordial condensates which were isolated from the nebula and from each other at different times by cocondensing oxides. Selective diffusion and/or oxidation of the more oxidizable metals (Mo, W, Fe, and Ni), phase segregations into different alloy phases (fcc, bcc, hcp, and, possibly, ordered phases), and the formation of metastable condensates could have been involved in the genesis of these materials

  19. Development of high performance refractory fibers with enhanced insulating properties and longer service lifetimes

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

    Martin, P.C.; DePoorter, G.L.; Munoz, D.R.

    1991-02-01

    We have initiated a three phase investigation of the development of high performance refractory fibers with enhanced insulating properties and longer usable lifetimes. This report presents the results of the first phase of the study, performed from Aug. 1989 through Feb. 1991, which shows that significant energy saving are possible through the use of high temperature insulating fibers that better retain their efficient insulating properties during the service lifetime of the fibers. The remaining phases of this program include the pilot scale development and then full scale production feasibility development and evaluation of enhanced high temperature refractory insulting fibers. Thismore » first proof of principle phase of the program presents a summary of the current use patterns of refractory fibers, a laboratory evaluation of the high temperature performance characteristics of selected typical refractory fibers and an analysis of the potential energy savings through the use of enhanced refractory fibers. The current use patterns of refractory fibers span a wide range of industries and high temperature furnaces within those industries. The majority of high temperature fiber applications are in furnaces operating between 2000 and 26000{degrees}F. The fibers used in furnaces operating within this range provide attractive thermal resistance and low thermal storage at reasonable cost. A series of heat treatment studies performed for this phase of the program has shown that the refractory fibers, as initially manufactured, have attractive thermal conductivities for high temperature applications but the fibers go through rapid devitrification and subsequent crystal growth upon high temperature exposure. Development of improved fibers, maintaining the favorable characteristics of the existing as-manufactured fibers, could save between 1 and 4% of the energy consumed in high temperature furnaces using refractory fibers.« less

  20. Geology and Refractory Clay Deposits of the Haldeman and Wrigley Quadrangles, Kentucky

    USGS Publications Warehouse

    Patterson, Sam H.; Hosterman, John W.; Huddle, John Warfield

    1962-01-01

    The Haldeman and Wrigley 7th-minute quadrangles are near the western edge of the eastern Kentucky coal field and cover an area of approximately 117 square miles in parts of Carter, Rowan, Elliott, and Morgan Counties, Ky. The rocks exposed in the two quadrangles are of Early and Late Mississippian and Early and Middle Pennsylvanian age. The Mississippian rocks are composed of the thick Brodhead formation, which consists of siltstone and shale, and eleven thin marine limestone and shale formations, having an aggregate thickness of about 150 feet. The Lee and Breathitt formations, of Pennsylvanian age, consist of sandstone, siltstone, and shale; they also contain thin beds of coal and several beds of underclay, including the economically important Olive Hill clay bed of Crider, 1913. Pennsylvanian rocks include beds of both continental and marine origin. The eleven thin Mississippian formations and the upper-most part of the thick Brodhead formation are truncated by a prominent unconformity on which rocks of Pennsylvanian age rest. The rocks occupy a region of gentle dips between the Cincinnati arch and the Appalachian Mountains. Refractory clay deposits are in the Olive Hill clay bed, which occurs in the lower part of the Lee formation. The Olive Hill clay bed is discontinuous and consists of a series of irregularly shaped lenses. The bed is approximately two-thirds semifiint clay and one-third flint clay, and it contains minor amounts of plastic clay. Some of the flint clay is nearly pure kaolinite, but the semi flint and plastic clay consists of mixtures of kaolinite, illite, and mixed-layer clay minerals. The structure of the kaolinite ranges from highly crystalline to very poorly crystalline 'fireclay' type. The degree of crystallinity of the kaolinite and the hardness of the clay vary inversely with the amount of illite and mixed-layer clay minerals present. The nearly pure kaolinite is believed to have formed by the removal of alkalies and some silica fram

  1. 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

  2. Intravenous immunoglobulin therapy for refractory recurrent pericarditis.

    PubMed

    del Fresno, M Rosa; Peralta, Julio E; Granados, Miguel Ángel; Enríquez, Eugenia; Domínguez-Pinilla, Nerea; de Inocencio, Jaime

    2014-11-01

    Recurrent pericarditis is a troublesome complication of idiopathic acute pericarditis and occurs more frequently in pediatric patients after cardiac surgery (postpericardiotomy syndrome). Conventional treatment with nonsteroidal antiinflammatory drugs, corticosteroids, and colchicine is not always effective or may cause serious adverse effects. There is no consensus, however, on how to proceed in those patients whose disease is refractory to conventional therapy. In such cases, human intravenous immunoglobulin, immunosuppressive drugs, and biological agents have been used. In this report we describe 2 patients with refractory recurrent pericarditis after cardiac surgery who were successfully treated with 3 and 5 monthly high-dose (2 g/kg) intravenous immunoglobulin until resolution of the effusion. Our experience supports the effectiveness and safety of this therapy. Copyright © 2014 by the American Academy of Pediatrics.

  3. Evaluation of olivine refractories for TES

    NASA Astrophysics Data System (ADS)

    Gay, B. M.; Cochrane, R. L.; Palmour, H., III; Paisley, M. J.

    1982-02-01

    The principal objectives of this program are to (1) experimentally determine 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, (2) conduct an assessment of existing German ceramic process technology and determine its adaptability to domestic raw materials and manufacturing practices, and (3) investigate, on a limited basis, method for further improvement of domestic-olivine brick. To date, accomplishments include (1) installation of improved, computer-based instrumentation, (2) the use of this system to determine performance characteristics of a set of heat storage refractories under cyclic use conditions, (3) acquisition of the services of a knowledgeable European consultant, (4) continued lab-scale process/property optimization studies, and (5) comparative testing of olivine-based and magnesite-based heat storage refractories in the calorimetric test facility at Purdue University.

  4. 131I-MIBG followed by consolidation with busulfan, melphalan and autologous stem cell transplantation for refractory neuroblastoma.

    PubMed

    French, Sarah; DuBois, Steven G; Horn, Biljana; Granger, Meaghan; Hawkins, Randall; Pass, Amy; Plummer, Ellen; Matthay, Katherine

    2013-05-01

    (131) I-metaiodobenzylguanidine (MIBG) produces a 37% response rate in relapsed/refractory neuroblastoma, and could be used to improve remission status prior to myeloablative chemotherapy with autologous stem cell transplant (ASCT). The purpose of our report was to evaluate safety and response with MIBG therapy followed by myeloablative busulfan and melphalan (BuMel) with ASCT in patients with refractory neuroblastoma. Retrospective chart review was done on patients treated with MIBG (18 mCi/kg) on Day 1 and ASCT on day 14. Six to eight weeks after MIBG, patients without progressive disease received IV busulfan on days -6 to -2 (target Css 700-900), melphalan (140 mg/m2 IV) on day -1, and ASCT on Day 0. Response and toxicity were evaluated after MIBG and again after myeloablative therapy. Eight patients completed MIBG/ASCT followed by BuMel/ASCT. MIBG was well tolerated, with grade 3 or 4 non-hematologic toxicity limited to one patient with sepsis. Grade 3 mucositis occurred in six patients after BuMel/ASCT. One patient developed sinusoidal obstructive syndrome (SOS) and died 50 days post-ASCT following myeloablative conditioning. All patients engrafted neutrophils (median 16.5 days) and platelets (median 32 days) after BuMel, excluding the patient with SOS. After all therapy, there were three complete, two partial, and one minor response in seven evaluable patients. MIBG at doses up to 18 mCi/kg can be safely administered 6 weeks prior to a BuMel consolidative regimen for refractory neuroblastoma. Preceding MIBG did not impair engraftment following BuMel. This regimen is being further evaluated in a Children's Oncology Group (COG) trial. Copyright © 2012 Wiley Periodicals, Inc.

  5. Intensive nutritional support improves the nutritional status and body composition in severely malnourished children with cerebral palsy.

    PubMed

    García-Contreras, Andrea A; Vásquez-Garibay, Edgar M; Romero-Velarde, Enrique; Ibarra-Gutiérrez, Ana Isabel; Troyo-Sanromán, Rogelio; Sandoval-Montes, Imelda E

    2014-04-01

    To demonstrate that a nutritional support intervention, via naso-enteral tube-feeding or gastrostomy, has a significant impact on the nutritional status and body composition in severely malnourished children with cerebral palsy spastic quadriplegia. Thirteen patients with moderate/severe malnutrition and cerebral palsy spastic quadriplegia who were fed via naso-enteral tube-feeding or gastrostomy were included in a cohort study. Anthropometric measurements and estimated body composition by bioelectric impedance analysis were obtained. ANOVA and Wilcoxon tests were used. During the four weeks of nutritional recovery, an average weight increase of 2700 g was achieved. There were significant increases in anthropometric indicators, including BMI and weight/length (p < 0.01). The increase in arm fat area was significantly higher than the increase in arm muscle area (104.5 vs 17.5%). Intensive nutritional support for four weeks had a significant effect on the nutritional status and body composition of severe and moderately malnourished children with cerebral palsy spastic quadriplegia. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  6. 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

  7. Refractory heartburn: comparison of intercellular space diameter in documented GERD vs. functional heartburn.

    PubMed

    Vela, Marcelo F; Craft, Brandon M; Sharma, Neeraj; Freeman, Janice; Hazen-Martin, Debra

    2011-05-01

    Refractory heartburn despite acid suppression may be explained by ongoing gastroesophageal reflux disease (GERD) or functional heartburn (FH), i.e., symptoms without evidence of GERD. Impedance-pH monitoring (impedance-pH) detects acid and nonacid reflux and is useful for evaluating acid-suppressed, refractory patients. Intercellular space diameter (ISD) of esophageal epithelium measured by transmission electron microscopy (TEM) is a marker of epithelial damage present in both erosive and nonerosive reflux disease. ISD has not been used to study refractory heartburn or FH. Our aim was to compare ISD in healthy controls and refractory heartburn patients with GERD and FH. In refractory heartburn patients (heartburn more than twice/week for at least 2 months despite proton pump inhibitor (PPI) b.i.d.), erosive esophagitis and/or abnormal impedance-pH (increased acid exposure or positive symptom index) defined GERD; normal esophagogastroduodenoscopy (EGD)/impedance-pH defined FH. Asymptomatic, healthy controls had normal EGD and pH-metry. Mean ISD in each subject, determined by blinded TEM of esophageal biopsies, was the average of 100 measurements (10 measurements in each of 10 micrographs). In all, 11 healthy controls, 11 FH, and 15 GERD patients were studied. Mean ISD was significantly higher in GERD compared with controls (0.87 vs. 0.32 μm, P=0.003) and FH (0.87 vs. 0.42 μm, P=0.012). Mean ISD was similar in FH and controls (0.42 vs. 0.32 μm, P=0.1). The proportion of patients with abnormal ISD was significantly higher for GERD compared with FH (60 vs. 9%, P=0.014). ISD is increased in refractory heartburn patients with GERD but not those with FH. Our findings suggest that measurement of ISD by TEM might be a useful tool to distinguish GERD from FH in patients with refractory heartburn.

  8. 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

  9. 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.

  10. [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.

  11. Long-term clinical outcomes of Ahmed valve implantation in patients with refractory glaucoma.

    PubMed

    Lee, Chang Kyu; Ma, Kyoung Tak; Hong, Young Jae; Kim, Chan Yun

    2017-01-01

    To evaluate the long-term efficacy of intraocular pressure (IOP) reduction and complications of Ahmed Glaucoma Valve (AGV) implantation in patients with refractory glaucoma. Retrospective study. The study involved 302 refractory glaucoma patients who underwent AGV implantation and had a minimum follow-up of 6 months between March 1995 and December 2013. An operation was defined as successful when (1) the postoperative IOP remained between 5 and 21 mmHg and was reduced 30% compared to the baseline IOP with or without medication, (2) there was no loss of light perception or vision-threatening severe complications, and (3) no additional filtering or aqueous drainage surgery was required. Clinical records were reviewed. IOP, anti-glaucoma medications, and complications. The mean follow-up period was 62.25 months (range, 6 to 190 months). The cumulative probability of success was 89% at 6 months, 81% at 1 year, 66% at 3 years, 44% at 10 years, and 26% at 15 years. IOP was reduced from a mean of 32.2 ± 10.5 mmHg to 18.6 ± 9.1 mmHg at 1 month, 15.2 ± 7.0 mmHg at 6 months, and 14.2 ± 3.5 mmHg at 15 years. Surgical failures were significantly increased when preoperative IOP was high, and when severe complications occurred after AGV implantation (P < 0.05). AGV implantation was successful for IOP control in patients with refractive glaucoma in the long term. However, the success rate of surgery decreased over time. Preoperative high IOP and severe complications related to the operation were significant risk factors for failure.

  12. Long-term clinical outcomes of Ahmed valve implantation in patients with refractory glaucoma

    PubMed Central

    Lee, Chang Kyu; Ma, Kyoung Tak; Hong, Young Jae

    2017-01-01

    Purpose To evaluate the long-term efficacy of intraocular pressure (IOP) reduction and complications of Ahmed Glaucoma Valve (AGV) implantation in patients with refractory glaucoma. Design Retrospective study. Subjects The study involved 302 refractory glaucoma patients who underwent AGV implantation and had a minimum follow-up of 6 months between March 1995 and December 2013. Methods An operation was defined as successful when (1) the postoperative IOP remained between 5 and 21 mmHg and was reduced 30% compared to the baseline IOP with or without medication, (2) there was no loss of light perception or vision-threatening severe complications, and (3) no additional filtering or aqueous drainage surgery was required. Clinical records were reviewed. Main outcome measures IOP, anti-glaucoma medications, and complications Results The mean follow-up period was 62.25 months (range, 6 to 190 months). The cumulative probability of success was 89% at 6 months, 81% at 1 year, 66% at 3 years, 44% at 10 years, and 26% at 15 years. IOP was reduced from a mean of 32.2 ± 10.5 mmHg to 18.6 ± 9.1 mmHg at 1 month, 15.2 ± 7.0 mmHg at 6 months, and 14.2 ± 3.5 mmHg at 15 years. Surgical failures were significantly increased when preoperative IOP was high, and when severe complications occurred after AGV implantation (P < 0.05). Conclusion AGV implantation was successful for IOP control in patients with refractive glaucoma in the long term. However, the success rate of surgery decreased over time. Preoperative high IOP and severe complications related to the operation were significant risk factors for failure. PMID:29095931

  13. The friction and wear properties of sputtered hard refractory compounds

    NASA Technical Reports Server (NTRS)

    Brainard, W. A.

    1978-01-01

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

  14. Method for hot pressing irregularly shaped refractory articles

    DOEpatents

    Steinkamp, William E.; Ballard, Ambrose H.

    1982-01-01

    The present invention is directed to a method for hot pressing irregularly haped refractory articles with these articles of varying thickness being provided with high uniform density and dimensional accuracy. Two partially pressed compacts of the refractory material are placed in a die cavity between displaceable die punches having compact-contacting surfaces of the desired article configuration. A floating, rotatable block is disposed between the compacts. The displacement of the die punches towards one another causes the block to rotate about an axis normal to the direction of movement of the die punches to uniformly distribute the pressure loading upon the compacts for maintaining substantially equal volume displacement of the powder material during the hot pressing operation.

  15. Efficacy and safety of oral alitretinoin in severe oral lichen planus--results of a prospective pilot study.

    PubMed

    Kunz, M; Urosevic-Maiwald, M; Goldinger, S M; Frauchiger, A L; Dreier, J; Belloni, B; Mangana, J; Jenni, D; Dippel, M; Cozzio, A; Guenova, E; Kamarachev, J; French, L E; Dummer, R

    2016-02-01

    Patients with severe oral lichen planus refractory to standard topical treatment currently have limited options of therapy suitable for long-term use. Oral alitretinoin (9-cis retinoic acid) was never systematically investigated in clinical trials, although case reports suggest its possible efficacy. To assess the efficacy and safety of oral alitretinoin taken at 30 mg once daily for up to 24 weeks in the treatment of severe oral lichen planus refractory to standard topical therapy. We conducted a prospective open-label single arm pilot study to test the efficacy and safety of 30 mg oral alitretinoin once daily for up to 24 weeks in severe oral lichen planus. Ten patients were included in the study. Primary end point was reduction in signs and symptoms measured by the Escudier severity score. Secondary parameters included pain and quality of life scores. Safety parameters were assessed during a follow-up period of 5 weeks. A substantial response at the end of treatment, i.e. >50% reduction in disease severity measured by the Escudier severity score, was apparent in 40% of patients. Therapy was well tolerated. Adverse events were mild and included headache, mucocutaneous dryness, musculoskeletal pain, increased thyroid-stimulating hormone and dyslipidaemia. Alitretinoin given at 30 mg daily reduced disease severity of severe oral lichen planus in a substantial proportion of patients refractory to standard treatment, was well tolerated and may thus represent one therapeutic option for this special group of patients. © 2015 European Academy of Dermatology and Venereology.

  16. 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

  17. Gamma knife radiosurgery for medically and surgically refractory prolactinomas.

    PubMed

    Pouratian, Nader; Sheehan, Jason; Jagannathan, Jay; Laws, Edward R; Steiner, Ladislau; Vance, Mary L

    2006-08-01

    Experience with gamma knife radiosurgery (GKRS) for prolactinomas is limited because of the efficacy of medical and surgical intervention. Patients who are refractory to medical and/or surgical therapy may be treated with GKRS. We characterize the efficacy of GKRS for medically and surgically refractory prolactinomas. We reviewed our series of patients with prolactinomas who were treated with GKRS after failing medical and surgical intervention who had at least 1 year of follow-up. Twenty-three patients were included in analysis of endocrine outcomes (median and average follow-up of 55 and 58 mo, respectively) and 28 patients were included in analysis of imaging outcomes (median and average follow-up of 48 and 52 mo, respectively). Twenty-six percent of patients achieved a normal serum prolactin (remission) with an average time of 24.5 months. Remission was significantly associated with being off of a dopamine agonist at the time of GKRS and a tumor volume less than 3.0 cm3 (P < 0.05 for both). Long-term image-based volumetric control was achieved in 89% of patients. Complications included new pituitary hormone deficiencies in 28% of patients and cranial nerve palsy in two patients (7%). Clinical remission in 26% of treated patients is a modest result. However, because the GKRS treated tumors were refractory to other therapies and because complication rates were low, GKRS should be part of the armamentarium for treating refractory prolactinomas. Patients with tumors smaller than 3.0 cm3 and who are not receiving dopamine agonist at the time of treatment will likely benefit most.

  18. 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

  19. 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.

  20. Phosphates in some Missouri refractory clays

    USGS Publications Warehouse

    Halley, Robert B.; Foord, Eugene E.; Keller, David J.; Keller, Walter D.

    1997-01-01

    This paper describes in detail phosphate minerals occurring in refractory clays of Missouri and their effect on the refractory degree of the clays. The minerals identified include carbonate-fluorapatite (francolite), crandallite, goyazite, wavellite, variscite and strengite. It is emphasized that these phosphates occur only in local isolated concentrations, and not generally in Missouri refractory clays.The Missouri fireclay region comprises 2 districts, northern and southern, separated by the Missouri River. In this region, clay constitutes a major part of the Lower Pennsylvanian Cheltenham Formation. The original Cheltenham mud was an argillic residue derived from leaching and dissolution of pre-Pennsylvanian carbonates. The mud accumulated on a karstic erosion surface truncating the pre-Cheltenham rocks. Fireclays of the northern district consist mainly of poorly ordered kaolinite, with variable but minor amounts of illite, chlorite and fine-grained detrital quartz. Clays of the southern district were subjected to extreme leaching that produced well-ordered kaolinite flint clays. Local desilication formed pockets of diaspore, or more commonly, kaolinite, with oolite-like nubs or burls of diaspore (“burley”" clay).The phosphate-bearing materials have been studied by X-ray diffraction (XRD), scanning electron microscopy-energy dispersive spectral analysis (SEM-EDS) and chemical analysis. Calcian goyazite was identified in a sample of diaspore, and francolite in a sample of flint clay. A veinlet of wavellite occurs in flint clay at one locality, and a veinlet of variscite-strengite at another locality.The Missouri flint-clay-hosted francolite could not have formed in the same manner as marine francolite. The evidence suggests that the Cheltenham francolite precipitated from ion complexes in pore water, nearly simultaneously with crystallization of kaolinite flint clay from an alumina-silica gel. Calcian goyazite is an early diagenetic addition to its diaspore

  1. Case Series Report of 66 Refractory Maintenance Patients Evaluating the Effectiveness of Topical Oxidizing Agents.

    PubMed

    Cochrane, R Bruce; Sindelar, Betty

    2015-01-01

    To evaluate the clinical effects of a prescription tray application of hydrogen peroxide gel as an adjunct to frequent maintenance appointments for refractory periodontal patients. Case series data were analyzed from 66 failing periodontal maintenance patients who had exhausted treatment options before using prescription trays with a 1.7% hydrogen peroxide gel once or twice daily for two-and-a-half to five years. Data included pocket probing depths (PPD), bleeding on probing (BOP), smoking status, and compliance with tray usage. Data were collected prior to tray usage and after tray delivery at six months, one year, and annual intervals. A clinical and statistical reduction in BOP was maintained over the length of the study (p ≤ 0.01). No differences were seen in patients who used trays two times or one time a day or in patients who smoked or did not smoke. The 1.7% peroxide delivered via a prescription tray was most effective in shallow pockets. Aggregate PPD distribution did not change significantly. Of clinical relevance, only one tooth out of 1,745 teeth studied was lost due to periodontal disease during the study period. Prescription tray application of peroxide gel, as an adjunct to frequent periodontal maintenance appointments for refractory patients, demonstrated significant reductions in BOP'for smokers and non-smokers who used tray delivery once or twice a day.

  2. Oculoplastic technique of connecting a glaucoma valve shunt to extraorbital locations in cases of severe glaucoma.

    PubMed

    Rubin, Peter A D; Chang, Eli; Bernardino, Carlo Roberto; Hatton, Mark P; Dohlman, Claes H

    2004-09-01

    To describe a technique for inserting glaucoma shunts to the sinuses or the lacrimal sac as a means of lowering intraocular pressure in patients with refractory glaucoma associated with severe ocular surface disease. Nineteen patients with severe ocular surface disease necessitating a keratoprosthesis and with intractable glaucoma underwent placement of a modified Ahmed shunt to direct aqueous in the maxillary or ethmoid sinus or lacrimal sac. Intraocular pressure is presently well controlled without glaucoma medications in two thirds of patients. None of the patients had endophthalmitis. Established oculoplastic surgery techniques may be used to redirect aqueous to extraorbital locations and effectively lower intraocular pressure in patients with severe ocular surface disease and refractory glaucoma. This procedure has not been associated with endophthalmitis.

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

    PubMed Central

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

    2014-01-01

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

  4. 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.

  5. 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.

  6. Severity of Obstructive Sleep Apnea is Related to Aldosterone Status in Subjects with Resistant Hypertension

    PubMed Central

    Gonzaga, Carolina C.; Gaddam, Krishna K.; Ahmed, Mustafa I.; Pimenta, Eduardo; Thomas, S. Justin; Harding, Susan M.; Oparil, Suzanne; Cofield, Stacey S.; Calhoun, David A.

    2010-01-01

    Background: We previously described a significant correlation between plasma aldosterone concentration (PAC) and severity of obstructive sleep apnea (OSA) in patients with resistant hypertension. This investigation examines the relationship between aldosterone status and OSA in patients with resistant hypertensive—with and without hyperaldosteronism. Methods and Results: One hundred and nine consecutive patients with resistant hypertension were prospectively evaluated with plasma renin activity (PRA), PAC, 24-hour urinary aldosterone excretion (UAldo), and polysomnography. Hyperaldosteronism (PRA < 1 ng·mL-1·h-1 and UAldo ≥ 12 μg/24-h) prevalence was 28% and OSA prevalence was 77%. In patients with hyperaldosteronism, OSA prevalence was 84%, compared with 74% in hypertensive patients with normal aldosterone levels. There were no significant differences in body mass index or neck circumference between aldosterone groups. PAC and UAldo were both significantly correlated with apnea-hypopnea index (AHI) in the high-aldosterone group (ρ = 0.568, p = 0.0009; ρ = 0.533, p = 0.002, respectively). UAldo correlated weakly with apnea-hypopnea index in the normal-aldosterone group, but there was no significant correlation between PAC and AHI in the normal-aldosterone group (ρ = 0.224, p = 0.049; ρ = 0.015, p = 0.898, respectively). Conclusions: Our analysis of patients with resistant hypertension confirms a markedly high prevalence of OSA in this group. Furthermore, severity of OSA was greater in those patients with hyperaldosteronism and related to the degree of aldosterone excess. The correlation between OSA severity and aldosterone supports the hypothesis that aldosterone excess contributes to greater severity of OSA. Citation: Gonzaga CC; Gaddam KK; Ahmed MI; Pimenta E; Thomas SJ; Harding SM; Oparil S; Cofield SS; Calhoun DA. Severity of obstructive sleep apnea is related to aldosterone status in subjects with resistant hypertension. J Clin Sleep Med 2010

  7. Refractory thermal insulation for smooth metal surfaces

    NASA Technical Reports Server (NTRS)

    1964-01-01

    To protect rocket metal surfaces from engine exhaust heat, a refractory thermal insulation mixture, which adheres to smooth metals, has been developed. Insulation protection over a wide temperature range can be controlled by thickness of the applied mixture.

  8. Epidemiologic Association Between FUT2 Secretor Status and Severe Rotavirus Gastroenteritis in Children in the United States

    PubMed Central

    Payne, Daniel C.; Currier, Rebecca L.; Staat, Mary A.; Sahni, Leila C.; Selvarangan, Rangaraj; Halasa, Natasha B.; Englund, Janet A.; Weinberg, Geoffrey A.; Boom, Julie A.; Szilagyi, Peter G.; Klein, Eileen J.; Chappell, James; Harrison, Christopher J.; Davidson, Barbara S.; Mijatovic-Rustempasic, Slavica; Moffatt, Mary D.; McNeal, Monica; Wikswo, Mary; Bowen, Michael D.; Morrow, Ardythe L.; Parashar, Umesh D.

    2016-01-01

    IMPORTANCE A genetic polymorphism affecting FUT2 secretor status in approximately one-quarter of humans of European descent affects the expression of histo-blood group antigens on the mucosal epithelia of human respiratory, genitourinary, and digestive tracts. These histo-blood group antigens serve as host receptor sites necessary for attachment and infection of some pathogens, including norovirus. OBJECTIVE We investigated whether an association exists between FUT2 secretor status and laboratory-confirmed rotavirus infections in US children. DESIGN, SETTING, AND PARTICIPANTS Multicenter case-control observational study involving active surveillance at 6 US pediatric medical institutions in the inpatient and emergency department clinical settings. We enrolled 1564 children younger than 5 years with acute gastroenteritis (diarrhea and/or vomiting) and 818 healthy controls frequency matched by age and month, from December 1, 2011, through March 31, 2013. MAIN OUTCOMES AND MEASURES Paired fecal-saliva specimens were tested for rotavirus and for secretor status. Comparisons were made between rotavirus test–positive cases and healthy controls stratified by ethnicity and vaccination status. Adjusted multivariable analyses assessed the preventive association of secretor status against severe rotavirus gastroenteritis. RESULTS One (0.5%) of 189 rotavirus test–positive cases was a nonsecretor, compared with 188 (23%) of 818 healthy control participants (P < .001). Healthy control participants of Hispanic ethnicity were significantly less likely to be nonsecretors (13%) compared with healthy children who were not of Hispanic ethnicity (25%) (P < .001). After controlling for vaccination and other factors, children with the nonsecretor FUT2 polymorphism appeared statistically protected (98% [95% CI, 84%–100%]) against severe rotavirus gastroenteritis. CONCLUSIONS AND RELEVANCE Severe rotavirus gastroenteritis was virtually absent among US children who had a genetic

  9. [Early functional hemispherectomy in hemimegalencephaly associated to refractory epilepsy].

    PubMed

    Fonseca, Luiz Fernando; Melo, Renato Pacheco de; Cukiert, Arthur; Burattini, Jose Augusto; Mariani, Pedro Paulo; Brandão, Ródio; Ceda, Lauro; Baldauf, Cristine Mella; Argentoni, Meire; Forster, Cássio; Baise, Carla

    2004-12-01

    Hemimegalencephaly (HME) is a rare congenital brain malformation of unknown etiology. Patients with HME can present with an early onset epileptic syndrome which is often refractory to medical treatment and associated to impaired neurological development. Functional hemispherectomy (FH) has proven to be a valuable treatment alternative in patients with refractory epilepsy in this setting. Very few children operated under the age of 6 months and bearing HME and catastrophic epilepsy (CE) have been described in the literature. This study reports on 2 kids younger than 6 months with HME and CE submitted to FH with good clinical outcome.

  10. High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

    ClinicalTrials.gov

    2018-02-28

    Acute Leukemia of Ambiguous Lineage; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  11. Idiopathic burning mouth syndrome: a common treatment-refractory somatoform condition responsive to ECT.

    PubMed

    McGirr, Alexander; Davis, Lindsay; Vila-Rodriguez, Fidel

    2014-04-30

    Somatic symptom disorders are common causes of disability and suffering, and can pose significant management challenges. Idiopathic burning mouth syndrome is a challenging somatic symptom disorder with relatively high prevalence, particularly among post-menopausal women. Here, we present the case of a woman with severe treatment refractory idiopathic burning mouth syndrome and comorbid major depressive disorder, who was successfully treated with bitemporal electroconvulsive therapy. This case highlights the potential effectiveness of electroconvulsive therapy in idiopathic burning mouth syndrome when other treatment options have been exhausted. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Testing Consent Order on Refractory Ceramic Fibers

    EPA Pesticide Factsheets

    This notice announces that EPA has signed signed an enforceable testing consent order under the Toxic Substances Control Act (TSCA), 15 U.S.C. section 2601 at seq., with three of the primary producers of refractory ceramic fibers (RCF).

  13. Emerging treatment options for refractory angina pectoris: ranolazine, shock wave treatment, and cell-based therapies.

    PubMed

    Gennari, Marco; Gambini, Elisa; Bassetti, Beatrice; Capogrossi, Maurizio; Pompilio, Giulio

    2014-01-01

    A challenge of modern cardiovascular medicine is to find new, effective treatments for patients with refractory angina pectoris, a clinical condition characterized by severe angina despite optimal medical therapy. These patients are not candidates for surgical or percutaneous revascularization. Herein we review the most up-to-date information regarding the modern approach to the patient with refractory angina pectoris, from conventional medical management to new medications and shock wave therapy, focusing on the use of endothelial precursor cells (EPCs) in the treatment of this condition. Clinical limitations of the efficiency of conventional approaches justify the search for new therapeutic options. Regenerative medicine is considered the next step in the evolution of organ replacement therapy. It is driven largely by the same health needs as transplantation and replacement therapies, but it aims further than traditional approaches, such as cell-based therapy. Increasing knowledge of the role of circulating cells derived from bone marrow (EPCs) on cardiovascular homeostasis in physiologic and pathologic conditions has prompted the clinical use of these cells to relieve ischemia. The current state of therapeutic angiogenesis still leaves many questions unanswered. It is of paramount importance that the treatment is delivered safely. Direct intramyocardial and intracoronary administration has demonstrated acceptable safety profiles in early trials, and may represent a major advance over surgical thoracotomy. The combined efforts of bench and clinical researchers will ultimately answer the question of whether cell therapy is a suitable strategy for treatment of patients with refractory angina.

  14. Brentuximab Vedotin and Lenalidomide in Treating Patients With Relapsed or Refractory T-Cell Lymphomas

    ClinicalTrials.gov

    2018-06-15

    CD30-Positive Neoplastic Cells Present; Folliculotropic Mycosis Fungoides; Recurrent Mycosis Fungoides; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome

  15. Replacing critical and strategic refractory metal elements in nickel-base superalloys. [NASA's COSAM program

    NASA Technical Reports Server (NTRS)

    Stephens, J. R.; Dreshfield, R. L.; Nathal, M. V.

    1983-01-01

    Because of the import status and essential nature of their use, cobalt, chromium, tantalum, and niobium were identified as strategic and critical in the aerospace industry. NASA's Conservation of Strategic Aerospace Materials (COSAM) program aims to reduce the need for strategic materials used in gas turbine engines. Technological thrusts in two major areas are under way to meet the primary objective of conserving the use of strategic materials in nickelbase superalloys. These thrusts consist of strategic element substitution and alternative material identification. The program emphasizes cooperative research teams involving NASA Lewis Research Center, universities, and industry. The adoption of refractory metals in nickel-base superalloys is summarized including their roles in mechanical strengthening and environmental resistance; current research activities under way in the COSAM Program are presented as well as research findings to date.

  16. [Management of pediatric status epilepticus].

    PubMed

    Vargas L, Carmen Paz; Varela E, Ximena; Kleinsteuber S, Karin; Cortés Z, Rocío; Avaria B, María de Los Ángeles

    2016-01-01

    Pediatric Status Epilepticus (SE) is an emergency situation with high morbidity and mortality that requires early and aggressive management. The minimum time criterion to define SE was reduced from 30 to 5 minutes, defined as continuous seizure activity or rapidly recurrent seizures without resumption of consciousness for more than 5 minutes. This definition considers that seizures that persist for > 5 minutes are likely to do so for more than 30 min. Those that persist for more than 30 minutes are more difficult to treat. Refractory SE is the condition that extends beyond 60-120 minutes and requires anesthetic management. Super-refractory SE is the state of no response to anesthetic management or relapse during withdrawal of these drugs. The aim of this review is to provide and update on convulsive SE concepts, pathophysiology, etiology, available antiepileptic treatment and propose a rational management scheme. A literature search of articles published between January 1993 and January 2013, focused on pediatric population was performed. The evidence about management in children is limited, mostly corresponds to case series of patients grouped by diagnosis, mainly adults. These publications show treatment alternatives such as immunotherapy, ketogenic diet, surgery and hypothermia. A 35% mortality, 26% of neurological sequelae and 35% of recovery to baseline condition is described on patient’s evolution.

  17. 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

  18. Electrodeposition of Refractory Carbide Coatings.

    DTIC Science & Technology

    1982-12-30

    refractory carbide coatings from molten salts is described. It consists of the simultaneous reduction of the appropriate metal species dissolved in the...Electrodeposition Molden salts 20. ASSTRACT (Continue an reve.e. 0g.. It necooom wed identify bp block nu.be) A novel method for electrodepositing...respectively. Electrolysis resulted in the formation of millimeter-size crystals on the walls of the graphite crucible which served as the cathode. Analysis of

  19. REFRACTORY DIE FOR EXTRUDING URANIUM

    DOEpatents

    Creutz, E.C.

    1959-08-11

    A die is presented for the extrusion of metals, said die being formed of a refractory complex oxide having the composition M/sub n/O/sub m/R/sub x/O/sub y/ where M is magnesium, zinc, manganese, or iron, R is aluminum, chromic chromium, ferric iron, or manganic manganese, and m, n, x, and y are whole numbers. Specific examples are spinel, magnesium aluminate, magnetite, magnesioferrite, chromite, and franklinite.

  20. 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.

  1. Quetiapine for insomnia associated with refractory depression exacerbated by phenelzine.

    PubMed

    Sokolski, Kenneth N; Brown, Brenda J

    2006-03-01

    To report the successful treatment of phenelzine-associated insomnia with low-dose quetiapine in a patient with refractory depression. A 42-year-old white man with severe major depression unresponsive to selective serotonin-reuptake inhibitors, bupropion, and tricyclic antidepressants improved following treatment with the monoamine oxidase inhibitor (MAOI) phenelzine. Insomnia, present to a moderate degree prior to antidepressant therapy, worsened markedly following phenelzine treatment and failed to respond to diphenhydramine, temazepam, triazolam, clonazepam, zolpidem, or trazodone given at high therapeutic doses. Sleep disturbance resolved with low-dose (50 mg) adjunctive quetiapine, with no adverse effects. Major depression refractory to standard therapy is a common and serious condition. Some cases respond to MAOIs; however, orthostatic hypotension and insomnia frequently occur. Potentially serious MAOI interactions with psychotropic drugs have raised concerns about combining these agents. In this case, a failure of a number of other medications known to treat MAOI-associated insomnia safely prompted a trial of quetiapine. Despite the possibility that enhanced serotonergic activity might have resulted in serotonin syndrome, no adverse interactions between phenelzine and quetiapine were noted. The use of low-dose, once-daily quetiapine, along with its unique binding properties, may account for its increased safety in combination with phenelzine. This case illustrates that low-dose quetiapine may be an alternative treatment for phenelzine-associated insomnia. Further case reports are needed to establish the safety and effectiveness of combining these agents.

  2. Angina pectoris refractory for conventional therapy--is neurostimulation a possible alternative treatment?

    PubMed

    Hautvast, R W; DeJongste, M J; ter Horst, G J; Blanksma, P K; Lie, K I

    1996-07-01

    The treatment of angina pectoris as a symptom of coronary artery disease usually is focused on restoring the balance between oxygen demand and supply of the myocardium by administration of drugs interfering in heart rate, cardiac pre- and afterload, and coronary vascular tone. For nonresponders to drug therapy or for those with jeopardized myocardium, revascularization procedures such as coronary bypass surgery and percutaneous transluminal coronary angioplasty are at hand. However, the atherosclerotic process is not stopped by these therapies and, at longer terms, angina may recur. It is not always possible to revascularize all the patients who do not positively react to medical treatment. Those with angina, not responding to adequate medication and who are not suitable anymore for revascularization, are considered to suffer from refractory angina pectoris. This group of patients has a poor quality of life, for their exercise tolerance is severely afflicted. For these patients, neurostimulation has been described repeatedly as an effective and safe therapy. The mechanism of action of neurostimulation is not completely known, but recent studies suggest an anti-ischemic effect, exerted through changes in myocardial blood flow. As soon as its safety is sufficiently established, it may become a useful alternative in the treatment of refractory angina pectoris.

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

    PubMed Central

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

    2012-01-01

    Background High-dose chemotherapy followed by autologous stem cell transplantation is the standard treatment for relapsed and/or refractory Hodgkin’s lymphoma although half of patients relapse after transplantation. Predictive factors, such as relapse within 12 months, Ann-Arbor stage at relapse, and relapse in previously irradiated fields are classically used to identify patients with poor outcome. Recently, 18-fluorodeoxyglucose positron emission tomography has emerged as a new method for providing information to predict outcome. The aim of this study was to confirm the predictive value of positron emission tomography status after salvage therapy and to compare single versus tandem autologous stem cell transplantation in patients with relapsed and/or refractory Hodgkin’s lymphoma. Design and Methods We report a series of 111 consecutive patients with treatment-sensitive relapsed and/or treatment-refractory Hodgkin’s lymphoma who achieved complete (positron emission tomography-negative group) or partial remission (positron emission tomography-positive group) at positron emission tomography evaluation after salvage chemotherapy and who underwent single or tandem autologous stem cell transplantation. Results Five-year overall and progression-free survival rates were 81% and 64%, respectively. There were significant differences in 5-year progression-free survival (79% versus 23%; P<0.001) and 5-year overall survival (90% versus 55%, P=0.001) between the positron emission tomography-negative and -positive groups, respectively. A complete response, as determined by positron emission tomography evaluation, after salvage therapy predicted significantly better 5-year overall survival rates in both intermediate (91% versus 50%; P=0.029) and unfavorable (89% versus 58%; P=0.026) risk subgroup analyses. In the positron emission tomography-positive subgroup, tandem transplantation improved 5-year progression-free survival from 0% (in the single transplantation group) to

  4. P2X purinoceptors as a link between hyperexcitability and neuroinflammation in status epilepticus.

    PubMed

    Henshall, David C; Engel, Tobias

    2015-08-01

    There remains a need for more efficacious treatments for status epilepticus. Prolonged seizures result in the release of ATP from cells which activates the P2 class of ionotropic and metabotropic purinoceptors. The P2X receptors gate depolarizing sodium and calcium entry and are expressed by both neurons and glia throughout the brain, and a number of subtypes are upregulated after status epilepticus. Recent studies have explored the in vivo effects of targeting ATP-gated P2X receptors in preclinical models of status epilepticus, with particular focus on the P2X7 receptor (P2X7R). The P2X7R mediates microglial activation and the release of the proepileptogenic inflammatory cytokine interleukin 1β. The receptor may also directly modulate neurotransmission and gliotransmission and promote the recruitment of immune cells into brain parenchyma. Data from our group and collaborators show that status epilepticus produced by intraamygdala microinjection of kainic acid increases P2X7R expression in the hippocampus and neocortex of mice. Antagonism of the P2X7R in the model reduced seizure severity, microglial activation and interleukin 1β release, and neuronal injury. Coadministration of a P2X7R antagonist with a benzodiazepine also provided seizure suppression in a model of drug-refractory status epilepticus when either treatment alone was minimally effective. More recently, we showed that status epilepticus in immature rats is also reduced by P2X7R antagonism. Together, these findings suggest that P2X receptors may be novel targets for seizure control and interruption of neuroinflammation after status epilepticus. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

  5. 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

  6. The relationship between periodontal status and peripheral levels of neutrophils in two consanguineous siblings with severe congenital neutropenia: case reports.

    PubMed

    Tözüm, Tolga Fikret; Berker, Ezel; Ersoy, Fügen; Tezcan, Iihan; Sanal, Ozden

    2003-03-01

    Congenital neutropenia is characterized by a severe reduction in absolute neutrophil counts, resulting in an almost total absence of neutrophils. It is well known that severe neutropenia affects periodontal status. Oral manifestations include ulcerations, gingival desquamation, gingival inflammation, attachment loss, and alveolar bone loss which may result in tooth loss. Treatment with granulocyte-colony stimulating factor (G-CSF) may improve this periodontal condition. This article reports the relationship between periodontal disease status and peripheral neutrophil levels in two consanguineous siblings with severe congenital neutropenia who did not receive routine G-CSF for 2 years prior to examination. Both siblings were given scaling, root planing, and periodontal prophylaxis in regular follow-up visits. This report demonstrates that periodontal therapy supported by adequate oral hygiene may result in restoration of neutrophil counts in siblings with congenital neutropenia.

  7. Clinical and etiological profile of refractory rickets from western India.

    PubMed

    Joshi, Rajesh R; Patil, Shailesh; Rao, Sudha

    2013-07-01

    To present clinical and etiological profile of refractory rickets from Mumbai. Case records of 36 patients presenting over 2½ y with refractory rickets were evaluated with respect to clinical presentation, biochemical, radiological features and where needed, ophthalmological examination, ultrasonography and special tests on blood and urine. Twenty three (63 %) patients had renal tubular acidosis (RTA)-distal RTA in 20 and proximal RTA in 3 patients; 5 (14 %) had vitamin D dependent rickets (VDDR I in 2 and VDDR II in 3 patients), 4 (11 %) had chronic renal failure (CRF) and 2 each (6 %) had hypophosphatemic rickets and chronic liver disease as cause of refractory rickets. A significant proportion of patients with RTA and VDDR showed skeletal changes of rickets in the first 2 y of life, while those with hypophosphatemic rickets presented later. Patients with hypophosphatemic rickets had predominant involvement of lower limbs, normal blood calcium and PTH levels and phosphorus leak in urine. All patients with RTA presented with failure to thrive, polyuria and marked rickets; blood alkaline phosphatase levels being normal in almost 50 % patients. Three (75 %) patients with rickets due to CRF had GFR < 30 ml/min/1.73 m(2) and hyperphosphatemia. Patients with cirrhosis due to biliary atresia had rickets inspite of taking high dose of vitamin D orally. Refractory rickets is a disorder of multiple etiologies; a good history and clinical examination supplemented with appropriate investigations helps to determine its cause.

  8. Methods and apparatus for reducing corrosion in refractory linings

    DOEpatents

    Poeppel, Roger B.; Greenberg, Sherman; Diercks, Dwight R.

    1987-01-01

    Methods and apparatus are provided for reducing corrosion in a refractory lining of a liquid-containing vessel used in direct steelmaking processes. The vessel operates at between about 1600.degree. C. and about 1800.degree. C. and an oxygen partial pressure of about 10.sup.-12 atmospheres, creating slag which is rich in FeO. The refractory lining includes a significant level of chromium oxide (Cr.sub.2 O.sub.3), and has small interconnected pores which may be filled with a gas mixture having a higher total pressure and oxygen partial pressure than the total pressure and oxygen partial pressure associted with the liquid against the lining of the vessel. The gas mixture is forced through the pores of the lining so that the pores are continuously filled with the mixture. In this manner, the gas mixture creates a blanket which increases the oxygen partial pressure at the lining enough to maintain the chromium in the lining in a selected valence state in which the chromium has decreased solubility in the FeO slag, thereby reducing corrosion by the FeO and increasing the useful life of the refractory lining.

  9. 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.

  10. Sharp Refractory Composite Leading Edges on Hypersonic Vehicles

    NASA Technical Reports Server (NTRS)

    Walker, Sandra P.; Sullivan, Brian J.

    2003-01-01

    On-going research of advanced sharp refractory composite leading edges for use on hypersonic air-breathing vehicles is presented in this paper. Intense magnitudes of heating and of heating gradients on the leading edge lead to thermal stresses that challenge the survivability of current material systems. A fundamental understanding of the problem is needed to further design development. Methodology for furthering the technology along with the use of advanced fiber architectures to improve the thermal-structural response is explored in the current work. Thermal and structural finite element analyses are conducted for several advanced fiber architectures of interest. A tailored thermal shock parameter for sharp orthotropic leading edges is identified for evaluating composite material systems. The use of the tailored thermal shock parameter has the potential to eliminate the need for detailed thermal-structural finite element analyses for initial screening of material systems being considered for a leading edge component.

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

    PubMed

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

    2017-12-01

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

  12. 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.

  13. Add-on levetiracetam in children and adolescents with refractory epilepsy: results of an open-label multi-centre study.

    PubMed

    Callenbach, Petra M C; Arts, Willem Frans M; ten Houten, Robert; Augustijn, Paul; Gunning, W Boudewijn; Peeters, Els A J; Weber, Alma M; Stroink, Hans; Geerts, Yvette; Geerts, Ada T; Brouwer, Oebele F

    2008-07-01

    To study the efficacy and tolerability of add-on levetiracetam in children and adolescents with refractory epilepsy. In this prospective multi-centre, open-label, add-on study, 33 children aged 4-16 years (median 8.5 years) with epilepsy refractory to at least two antiepileptic drugs were treated with levetiracetam in addition to their present treatment regimen with a follow-up of 26 weeks. The starting dose of 10 mg/kg/day was increased with 2-week steps of 10 mg/kg/day, if necessary, up to a maximum dose of 60 mg/kg/day. Retention rate was 69.7% after 26 weeks on a median levetiracetam dosage of 22 mg/kg/day. Four children dropped-out because levetiracetam was ineffective, four because seizure frequency increased and/or seizures became more severe, and two because they developed aggressive behaviour. Compared to their baseline seizure frequency, 13 children (39.4%) had a >50% seizure reduction 12 weeks after initiation of levetiracetam, and 17 children (51.5%) at 26 weeks. At 26 weeks, nine children (27.3%) had been seizure-free for at least the last 4 weeks, terminal remission ranged from 0 to 187 days (mean 46 days). Levetiracetam was effective in both partial and primary generalized seizures, but had most effect in partial seizures. Most reported side effects were hyperactivity (48.5%), somnolence (36.4%), irritability (33.3%) and aggressive behaviour (27.3%). Severity of most side effects was mild. Five children had a serious adverse event, which all concerned hospital admissions that were not related to levetiracetam use. Levetiracetam proved to be an effective and well-tolerated add-on treatment in this group of children with refractory epilepsy.

  14. R-ICE and Lenalidomide in Treating Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2018-06-25

    CD20 Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  15. Obinutuzumab, Venetoclax, and Lenalidomide in Treating Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2017-10-17

    B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  16. Efficacy of spinal cord stimulation as an adjunct therapy for chronic refractory angina pectoris.

    PubMed

    Imran, Tasnim F; Malapero, Raymond; Qavi, Ahmed H; Hasan, Zachariah; de la Torre, Bryan; Patel, Yash R; Yong, R Jason; Djousse, Luc; Gaziano, J Michael; Gerhard-Herman, Marie-Denise

    2017-01-15

    Patients with chronic refractory angina whose symptoms are not controlled with conventional therapies have a poor quality of life. Adjunctive therapies, such as spinal cord stimulation (SCS) may be considered in these cases. We sought to examine whether SCS is associated with changes in exercise capacity and angina severity in these patients. We searched Pubmed, Medline and other databases until December 2015. Two reviewers independently extracted data and assessed risk of bias. Exercise capacity included exercise duration and rate pressure product, determined via an exercise test. Angina severity included daily angina frequency and nitrate consumption. A total of 518 participants (1048.25 person-years of follow-up), from 14 studies met our inclusion criteria. The mean age was 66.8years and 68.5% were men. SCS implant duration ranged from 3weeks to 5years (median: 6months). Using random effects meta-analysis, we found that SCS was associated with a higher exercise duration (1.90min, 95% CI 1.71, 2.06) and lower angina severity, 1.55 less daily angina episodes, (95% CI -1.75, -1.33), 1.54 less daily nitrates consumed, (95% CI -1.81, -1.26), and a 22 points higher SF-36 angina frequency score (95% CI 10.76, 32.81; p<0.0001) on follow-up. The change in rate pressure product was not significant. This meta-analysis suggests that SCS, as an adjunct therapy to medical management, may be associated with a longer exercise duration and lower angina frequency and nitrate consumption in patients with chronic refractory angina pectoris who are not candidates for percutaneous intervention or revascularization. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Virtual reality therapy for refractory auditory verbal hallucinations in schizophrenia: A pilot clinical trial.

    PubMed

    du Sert, Olivier Percie; Potvin, Stéphane; Lipp, Olivier; Dellazizzo, Laura; Laurelli, Mélanie; Breton, Richard; Lalonde, Pierre; Phraxayavong, Kingsada; O'Connor, Kieron; Pelletier, Jean-François; Boukhalfi, Tarik; Renaud, Patrice; Dumais, Alexandre

    2018-02-24

    Schizophrenia is a chronic and severe mental illness that poses significant challenges. While many pharmacological and psychosocial interventions are available, many treatment-resistant schizophrenia patients continue to suffer from persistent psychotic symptoms, notably auditory verbal hallucinations (AVH), which are highly disabling. This unmet clinical need requires new innovative treatment options. Recently, a psychological therapy using computerized technology has shown large therapeutic effects on AVH severity by enabling patients to engage in a dialogue with a computerized representation of their voices. These very promising results have been extended by our team using immersive virtual reality (VR). Our study was a 7-week phase-II, randomized, partial cross-over trial. Nineteen schizophrenia patients with refractory AVH were recruited and randomly allocated to either VR-assisted therapy (VRT) or treatment-as-usual (TAU). The group allocated to TAU consisted of antipsychotic treatment and usual meetings with clinicians. The TAU group then received a delayed 7weeks of VRT. A follow-up was ensured 3months after the last VRT therapy session. Changes in psychiatric symptoms, before and after TAU or VRT, were assessed using a linear mixed-effects model. Our findings showed that VRT produced significant improvements in AVH severity, depressive symptoms and quality of life that lasted at the 3-month follow-up period. Consistent with previous research, our results suggest that VRT might be efficacious in reducing AVH related distress. The therapeutic effects of VRT on the distress associated with the voices were particularly prominent (d=1.2). VRT is a highly novel and promising intervention for refractory AVH in schizophrenia. Copyright © 2018. Published by Elsevier B.V.

  18. Immunity and inflammation in status epilepticus and its sequelae: possibilities for therapeutic application

    PubMed Central

    Vezzani, Annamaria; Dingledine, Raymond; Rossetti, Andrea O

    2016-01-01

    Status epilepticus (SE) is a life-threatening neurological emergency often refractory to available treatment options. It is a very heterogeneous condition in terms of clinical presentation and causes, which besides genetic, vascular and other structural causes also include CNS or severe systemic infections, sudden withdrawal from benzodiazepines or anticonvulsants and rare autoimmune etiologies. Treatment of SE is essentially based on expert opinions and antiepileptic drug treatment per se seems to have no major impact on prognosis. There is, therefore, urgent need of novel therapies that rely upon a better understanding of the basic mechanisms underlying this clinical condition. Accumulating evidence in animal models highlights that inflammation ensuing in the brain during SE may play a determinant role in ongoing seizures and their long-term detrimental consequences, independent of an infection or auto-immune cause; this evidence encourages reconsideration of the treatment flow in SE patients. PMID:26312647

  19. CSF Lumbar Drainage: A Safe Surgical Option in Refractory Intracranial Hypertension Associated with Acute Posttraumatic External Hydrocephalus.

    PubMed

    Manet, R; Schmidt, E A; Vassal, F; Charier, D; Gergelé, L

    2016-01-01

    External lumbar drainage (ELD) of cerebrospinal fluid (CSF) in posttraumatic refractory intracranial hypertension (ICHT) is controversial. We report our experience of ELD in ICHT associated with acute disturbance of CSF flow within subarachnoid spaces (SASs). Four adult patients admitted to the neurointensive care unit for severe TBI who presented with secondary ICHT are retrospectively reported. When refractory to second-tier therapy, if external ventricular drainage were not possible or failed, and in the absence of an indication for craniotomy to treat a mass lesion or decompressive craniectomy, we assessed the evolution of CSF volume within cranial SAS and checked the presence of basal cisterns and the absence of tonsillar herniation to evaluate interest in and the safety of ELD. As second-tier therapy failed to lower intracranial pressure (ICP; mean ICP 37 ± 5 mmHg), and computed tomography (CT) showed abnormally enlarged cranial SAS following traumatic subarachnoid hemorrhage, patients received ELD. ICP decreased, with immediate and long-term effect (mean ICP 5 mmHg ± 2 mmHg). There were no complications to report. Acute traumatic external hydrocephalus may explain some of the specific situations of secondary increased ICP, with a "normal" CT scan, that is refractory to medical treatment. In these situations, lumbar drainage should be considered to be a safe, minimally invasive, and effective surgical option.

  20. Dietary prevention of hormone refractory prostate cancer in Lobund-Wistar rats: a review of studies in a relevant animal model.

    PubMed

    Pollard, Morris; Suckow, Mark A

    2006-12-01

    Lobund-Wistar (LW) rats, which have high testosterone levels, are predisposed to develop hormone-refractory prostate cancer (HRPC) spontaneously and by methylnitrosourea (MNU) induction, and the development of HRPC progresses through 2 stages. This paper reviews several studies in which LW rats were placed on soy-containing diets and were evaluated for development of either spontaneous or MNU-induced prostate cancer. The premalignant, testosterone-dependent stage is inhibited by testosterone deprivation. In the absence of testosterone deprivation, tumorigenesis progresses spontaneously to the testosterone-independent refractory stage. In LW rats: moderate caloric restriction prevented development of spontaneous prostate cancer; dietary 4-hydroxyphenylretinamide prevented MNU-induced prostate cancer; and dietary supplementation with soy protein isolate with high isoflavones prevented spontaneous and induced tumors and led to moderate reduction of serum testosterone. In rats 12 mo of age and younger, changing from the control diet to the soy+isoflavone diet significantly prevented progression of spontaneous tumors to the refractory stage of disease. Tumors that developed spontaneously and after MNU induction showed similar developmental stages and morphology, but MNU-induced tumors had shorter latency periods before development. The accumulated data indicate that soy-based diets are effective in the prevention of prostate cancer.