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Sample records for severe refractory status

  1. Efficacy of ketogenic diet in severe refractory status epilepticus initiating fever induced refractory epileptic encephalopathy in school age children (FIRES).

    PubMed

    Nabbout, Rima; Mazzuca, Michel; Hubert, Philippe; Peudennier, Sylviane; Allaire, Catherine; Flurin, Vincent; Aberastury, Marina; Silva, Walter; Dulac, Olivier

    2010-10-01

    Fever induced refractory epileptic encephalopathy in school age children (FIRES) is a devastating condition initiated by prolonged perisylvian refractory status epilepticus (SE) triggered by fever of unknown cause. SE may last more than 1 month, and this condition may evolve into pharmacoresistant epilepsy associated with severe cognitive impairment. We aimed to report the effect of ketogenic diet (KD) in this condition. Over the last 12 years we collected data of nine patients with FIRES who received a 4:1 ratio of fat to combined protein and carbohydrate KD. They presented with SE refractory to conventional antiepileptic treatment. In seven patients, KD was efficacious within 2-4 days (mean 2 days) following the onset of ketonuria and 4-6 days (mean 4.8 days) following the onset of the diet. In one responder, early disruption of the diet was followed by relapse of intractable SE, and the patient died. Epilepsy affected the other six responders within a few months. KD may be an alternative therapy for refractory SE in FIRES and might be proposed in other types of refractory SE in childhood. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

  2. 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

  3. Refractory status epilepticus.

    PubMed

    Fernandez, Andres; Claassen, Jan

    2012-04-01

    Refractory status epilepticus (RSE) has a high morbidity and mortality. There are currently no definitive data to guide both the optimal choice of therapy and treatment goals. This review focuses on RSE diagnosis and outcome and discusses both commonly used and anecdotal therapies for RSE. The challenges in performing randomized controlled trials (RCTs) in neurocritical care and more specifically for the treatment of RSE are illustrated by the early termination of the first RCT of RSE due to low recruitment that compared propofol to barbiturates. Recent case series include the successful treatment of recurrent RSE with ketamine, intravenous lacosamide as an add-on treatment, the use of combination antiepileptics (phenytoin, levetiracetam, and pregabalin), and surgical treatments (vagal nerve and deep brain stimulation) for the control of RSE. A number of different therapeutic options are available for the treatment of RSE but none have been shown to be superior to others at this point.

  4. Status epilepticus: Refractory and super-refractory.

    PubMed

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

    2017-01-01

    Status epilepticus (SE) is an important neurological emergency. It is defined as seizures lasting for 5 minutes or more or recurrent seizures without recovery of consciousness to baseline between the attacks. Refractory SE (RSE) is defined as SE persisting despite sufficient dose of benzodiazepines and at least one antiepileptic drug (AED), irrespective of time. Super refractory SE (SRSE) is defined as SE that continues for 24 hours or more after the use of anesthetic therapy, including cases that recur on weaning of the anesthestic agent. RSE occurs in 23%-48% of the patients and SRSE in approximately 22% of the patients with SE. In general, RSE occurs in patients with new-onset seizures rather than in patients with chronic epilepsy. The etiology of RSE in developing countries is dominated by central nervous system (CNS) infections and head injury compared to stroke and drug withdrawal in the developed countries. The treatment of RSE and SRSE is not evidence based. Following benzodiazepines, the second line antiepileptic drugs include sodium valproate, phenytoin, levetiracetam, and anesthetic drugs such as midazolam, phenobarbital, and propofol. Most intravenous anesthetic drugs produce hypotension and respiratory suppression; therefore, patients with RSE are managed in intensive care units (ICUs). In RSE patients, electroencephalogram (EEG) burst suppression with interburst interval of 2-20 s or even flat EEG has been tried. Recently, concerns have been raised on the safety of burst suppression in RSE and SRSE. The paucity of ICUs in developing countries limits the use of these management protocols. There is a need to explore intravenous AEDs with safer cardiovascular and respiratory profile for the management of SE.

  5. 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

  6. Refractory status epilepticus: a prospective observational study.

    PubMed

    Novy, Jan; Logroscino, Giancarlo; Rossetti, Andrea O

    2010-02-01

    Status epilepticus (SE) that is resistant to two antiepileptic compounds is defined as refractory status epilepticus (RSE). In the few available retrospective studies, estimated RSE frequency is between 31% and 43% of patients presenting an SE episode; almost all seem to require a coma induction for treatment. We prospectively assessed RSE frequency, clinical predictors, and outcome in a tertiary clinical setting. Over 2 years we collected 128 consecutive SE episodes (118 patients) in adults. Clinical data and their relationship to outcome (mortality and return to baseline clinical conditions) were analyzed. Twenty-nine of 128 SE episodes (22.6%) were refractory to first- and second-line antiepileptic treatments. Severity of consciousness impairment and de novo episodes were independent predictors of RSE. RSE showed a worse outcome than non-RSE (39% vs. 11% for mortality; 21% vs. 63% for return to baseline clinical conditions). Only 12 patients with RSE (41%) required coma induction for treatment. This prospective study identifies clinical factors predicting the onset of SE refractoriness. RSE appears to be less frequent than previously reported in retrospective studies; furthermore, most RSE episodes were treated outside the intensive care unit (ICU). Nonetheless, we confirm that RSE is characterized by high mortality and morbidity.

  7. VNS for refractory status epilepticus.

    PubMed

    Zeiler, F A; Zeiler, K J; Teitelbaum, J; Gillman, L M; West, M

    2015-05-01

    Our goal was to perform a systematic review of the literature on the insertion of vagal nerve stimulators (VNS) for refractory status epilepticus (RSE) and its impact on the control of RSE. All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to June 2014), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers (FZ and MW). Overall, 17 studies were identified, with 7 manuscripts and 10 meeting abstracts. A total of 28 patients were treated. In those with generalized RSE, 76% displayed cessation of RSE with VNS insertion. In cases of focal RSE, 25% responded to VNS insertion. Few adverse effects related to VNS insertion were described. We currently cannot recommend the use of VNS for RSE. Oxford level 4, GRADE D evidence exists to suggest improvement in seizure control with the use of urgent VNS in generalized RSE. No comments can be made on the utility of VNS in focal RSE. Further prospective study is warranted. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. The prevalence of severe refractory asthma.

    PubMed

    Hekking, Pieter-Paul W; Wener, Reinier R; Amelink, Marijke; Zwinderman, Aelko H; Bouvy, Marcel L; Bel, Elisabeth H

    2015-04-01

    Severe asthma is characterized by difficulty to achieve disease control despite high-intensity treatment. However, prevalence figures of severe asthma are lacking, whereas longstanding estimates vary between 5% and 10% of all asthmatic patients. Knowing the exact prevalence of severe refractory asthma as opposed to difficult-to-control asthma is important for clinical decision making, drug development, and reimbursement policies by health authorities. We sought to estimate the prevalence of severe refractory asthma as defined by the Innovative Medicine Initiative consensus. Adult patients with a prescription for high-intensity treatment (high-dose inhaled corticosteroids and long-acting β2-agonists or medium- to high-dose inhaled corticosteroids combined with oral corticosteroids and long-acting β2-agonists) were extracted from 65 Dutch pharmacy databases, representing 3% of the population (500,500 inhabitants). Questionnaires were sent to 5,002 patients, of which 2,312 were analyzed. The diagnosis of asthma and degree of asthma control were derived from questionnaires to identify patients with difficult-to-control asthma. Inhalation technique was assessed in a random sample of 60 adherent patients (prescription filling, ≥80%). Patients with difficult-to-control asthma, adherence to treatment, and a correct inhalation technique were qualified as having severe refractory asthma. Results were mirrored to the Dutch population. Of asthmatic adults, 3.6% (95% CI, 3.0% to 4.1%) qualified for a diagnosis of severe refractory asthma, representing 10.4 patients per 10,000 inhabitants. The prevalence of severe refractory asthma might be lower than estimated by expert opinion. This implies that currently recognized severe asthma subphenotypes could meet the criteria of rare diseases. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  9. 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

  10. 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

  11. Propofol infusion syndrome in refractory status epilepticus.

    PubMed

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

    2013-06-01

    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. 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. 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. 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.

  12. 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

  13. Midazolam and pentobarbital for refractory status epilepticus.

    PubMed

    Holmes, G L; Riviello, J J

    1999-04-01

    Status epilepticus, a serious, life-threatening emergency characterized by prolonged seizure activity, occurs most commonly in pediatric patients. Although initial therapies with agents such as diazepam, phenytoin, or phenobarbital generally terminate seizure activity within 30-60 minutes, patients with refractory status epilepticus (RSE) lasting longer require additional intervention. High-dose pentobarbital has been the most commonly prescribed agent for the management of RSE in children; however, midazolam has emerged as a new treatment option. This review compares the use of midazolam with pentobarbital in published reports of pediatric RSE. Both drugs effectively terminated refractory seizure activity, although pentobarbital use was complicated by hypotension, delayed recovery, pneumonia, and other adverse effects. Midazolam use was effective and well tolerated, affirming its value in pediatric RSE management.

  14. Refractory and super-refractory status epilepticus in adults: a 9-year cohort study.

    PubMed

    Delaj, L; Novy, J; Ryvlin, P; Marchi, N A; Rossetti, A O

    2017-01-01

    While status epilepticus (SE) persisting after two antiseizure agents is called refractory (RSE), super-refractory status epilepticus (SRSE) defines SE continuing after general anaesthesia. Its prevalence and related clinical profiles have received limited attention, and most studies were restricted to intensive care facilities. We therefore aimed at describing RSE and SRSE frequencies and identifying associated clinical variables. Between 2006 and 2015, consecutive adult SE episodes were prospectively recorded in a registry. Occurrence of RSE and SRSE and their relationship to clinical variables of interest, including outcome, were analysed. Of 804 SE episodes, 268 (33.3%) were RSE and 33 (4%) SRSE. Coma induction for SE treatment occurred in 79 (9.8%) episodes. Severe consciousness impairment (OR 1.67; 95% CI 1.24-2.46; P = 0.001), increasing age (OR 1.01, 95% CI 1.01-1.02), and lack of remote symptomatic SE aetiology (OR 0.48; 95% CI 0.32-0.72) were independently associated with RSE, while severe consciousness impairment (OR 4.26; 95% CI 1.44-12.60) and younger age (OR 0.96; 95% CI 0.95-0.99) correlated with SRSE; however, most SRSE episodes were not predicted by these variables. Mortality was 15.5% overall, higher in RSE (24.5%) and SRSE (37.9%) than in non-refractory SE (9.8%) (P < 0.001). Super-refractory status epilepticus appears clearly less prevalent in this cohort than previously reported, probably as it is not restricted to intensive care unit. SRSE emerges in younger patients with marked consciousness impairment, pointing to the underlying severe clinical background, but these variables do not predict most SRSE developments. There is currently a knowledge gap for prediction of SRSE occurrence that needs to be filled. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Cardiac injury in refractory status epilepticus.

    PubMed

    Hocker, Sara; Prasad, Abhiram; Rabinstein, Alejandro A

    2013-03-01

    We sought to describe the spectrum of cardiac injury in refractory status epilepticus (RSE). We reviewed all patients with RSE between 1999 and 2011 at Mayo Clinic. RSE was defined as generalized convulsive or nonconvulsive status epilepticus (SE) that continued despite initial therapies. Exclusion criteria were age <18 years, anoxic SE, psychogenic SE, simple partial SE, absence SE, and repeat RSE. Patients were divided into those with (transient left ventricular [LV] dysfunction; electrocardiography [ECG] abnormality-new T-wave inversion, ST elevation or ST depression, or QTc prolongation; and/or elevated blood troponin T levels) versus those without evidence of cardiac injury. We identified 59 consecutive patients with RSE. In 24 patients no cardiac-specific diagnostic studies were obtained. Twenty-two of the remaining 35 patients demonstrated markers of cardiac injury. General anesthesia was necessary for control of seizures in 31 of 35 patients for 10.5 ± 17.4 days. Twenty-three patients had troponin levels drawn at onset of SE, of which nine were abnormal. ECG findings at onset of SE included ST elevation (11.4%), ST depression (5.7%), new T-wave inversion (37.1%), and nonspecific ST changes (37.1%). Cardiac arrhythmias included ventricular tachycardia/fibrillation (11.4%), atrioventricular block (2.9%), atrial fibrillation/flutter (20.0%), sinus bradycardia (48.6%), and sinus tachycardia (65.7%). Intervention was required for cardiac arrhythmias in 42.9%. QTc was prolonged in 22.9% of patients. One patient met criteria for non-ST-elevation myocardial infarction (NSTEMI). Three of 14 patients evaluated with ECG during SE demonstrated reversible systolic dysfunction. In-hospital mortality was 34.3%. Outcome was worse in the group with markers of cardiac injury but the difference was not statistically significant (p = 0.14). Markers of cardiac injury are common in RSE and may be underrecognized in this population. These disturbances may require specific

  16. Refractory status epilepticus: a developing country perspective.

    PubMed

    Sinha, S; Prashantha, D K; Thennarasu, K; Umamaheshwara Rao, G S; Satishchandra, P

    2010-03-15

    To analyse the underlying causes, therapeutic response and outcomes of convulsive refractory status epilepticus (RSE). This retrospective analysis was carried on 98 patients with RSE (age: 16.9+/-14.5 years). All had received a combination of parenteral benzodiazepine and phenytoin or phenobarbitone followed by other anti-epileptic drugs (AEDs). The clinical, EEG, imaging features of convulsive RSE and long-term seizure outcome were analysed. Seventy six patients had de novo RSE for the first time in life. The mean duration of RSE, before and during NICU admission was 3.4+/-3.2 days and 2.9+/-2.4 days respectively. The mean duration of NICU stay and mechanical ventilation was 17.4+/-14.5 was 14.4+/-12.8 days respectively. The precipitating factors included viral fever - 13, AEDs stoppage - 7 and alcohol - 1. EEG was abnormal in 81.5% of patients. CT and MRI were abnormal in 63.4% and 82.3% respectively. Thirty-four patients died and compared to those surviving, patients were older, had lesser duration of NICU stay and elevated CSF protein. Dependence for activities of daily living (ADL) at discharge was: recovered - 29, mild to moderate - 13 and severe - 22. Seizure outcome in 64 patients after 43.5+/-58.2 weeks were - seizure-free: 65.6%, one seizure: 21.8%, >1 seizure/month: 14.1%, and seizure recurrence requiring admission: 1.5%. After six and twelve months of follow up, the long-term seizure outcome were: seizure-free: 48.3% and 28.6%; one seizure: 27.6% and 38.1%; >1 seizure/month: 20.7% and 28.6%; and seizure recurrence requiring admission: 3.4% and 4.7% respectively. Among those survived 49 de novo RSE, about one-third developed post-SE symptomatic seizures after 30.1+/-54.4 weeks. Seizures could still be controlled in two-thirds of patients with convulsive RSE. About 30% of patients achieved long-term seizure freedom.

  17. Hypothermia for pediatric refractory status epilepticus.

    PubMed

    Guilliams, Kristin; Rosen, Max; Buttram, Sandra; Zempel, John; Pineda, Jose; Miller, Barbara; Shoykhet, Michael

    2013-09-01

    Refractory status epilepticus (RSE) is a life-threatening emergency, demonstrating, by definition, significant pharmacoresistance. We describe five cases of pediatric RSE treated with mild hypothermia. Retrospective chart review was performed of records of children who received hypothermia for RSE at two tertiary-care pediatric hospitals between 2009 and 2012. Five children with RSE received mild hypothermia (32-35°C). Hypothermia reduced seizure burden during and after treatment in all cases. Prior to initiation of hypothermia, four children (80%) received pentobarbital infusions to treat RSE, but relapsed after pentobarbital discontinuation. No child relapsed after treatment with hypothermia. One child died after redirection of care. Remaining four children were discharged. This is the largest pediatric case series reporting treatment of RSE with mild hypothermia. Hypothermia decreased seizure burden during and after pediatric RSE and may prevent RSE relapse. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  18. Refractory Status Epilepticus Spontaneously Resolved by Parturition

    PubMed Central

    Jeong, Hye Seon; Oh, Eung Seok; Lee, Ji Hee; Kim, Jae Moon

    2011-01-01

    Status epilepticus (SE) in pregnancy is very rare, and there are only a few case reports of refractory SE (RSE) during pregnancy. The patient was a 27-year-old primigravida woman with a 21-year history of seizures from cortical dysplasia. At 23 weeks of pregnancy, the patient’s seizure frequency progressively increased, and the patient came to the ER in a confused mental state and with intermittent convulsive movements of her left arm. Electroencephalography (EEG) revealed repeated seizures. She was admitted to the ICU, and continuous EEG monitoring was done. Treatment was immediately started with various anti-SE medications, but her SE was not controlled. A cesarean section was done, and SE spontaneously stopped two weeks after the parturition. Parturition may be beneficial and the best treatment option in pregnant patients with RSE. PMID:24649442

  19. Hypothermia for pediatric refractory status epilepticus

    PubMed Central

    Guilliams, Kristin; Rosen, Max; Buttram, Sandra; Zempel, John; Pineda, Jose; Miller, Barbara; Shoykhet, Michael

    2014-01-01

    SUMMARY Purpose Refractory status epilepticus (RSE) is a life-threatening emergency, demonstrating, by definition, significant pharmacoresistance. We describe five cases of pediatric RSE treated with mild hypothermia. Methods Retrospective chart review was performed of records of children who received hypothermia for RSE at two tertiary-care pediatric hospitals between 2009 and 2012. Key Findings Five children with RSE received mild hypothermia (32–35°C). Hypothermia reduced seizure burden during and after treatment in all cases. Prior to initiation of hypothermia, four children (80%) received pentobarbital infusions to treat RSE, but relapsed after pentobarbital discontinuation. No child relapsed after treatment with hypothermia. One child died after redirection of care. Remaining four children were discharged. Significance This is the largest pediatric case series reporting treatment of RSE with mild hypothermia. Hypothermia decreased seizure burden during and after pediatric RSE and may prevent RSE relapse. PMID:23906244

  20. 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.

  1. Levetiracetam in children with refractory status epilepticus.

    PubMed

    Gallentine, William B; Hunnicutt, Addie S; Husain, Aatif M

    2009-01-01

    The objective of this study was to investigate the utility of levetiracetam (LEV) in children with refractory status epilepticus (RSE). Records of children with RSE who received LEV as adjunctive therapy were reviewed. Over a 7-year period, 11 children had received LEV for RSE. Age ranged from 2 days to 9 years (median = 2.5 months). Prior to administration of LEV, the number of anticonvulsants used to treat RSE ranged from 2 to 7 (median = 3). Starting doses of LEV ranged from 15 to 70 mg/kg (median = 30 mg/kg). LEV was felt to be of benefit in 45% (5/11) of cases, resulting in either resolution of RSE or successful weaning of patients off continuous infusions of other anticonvulsants. In 27% (3/11), response to LEV was unclear as other medications were either added or increased concomitantly with LEV use. The median latency to cessation of RSE following LEV initiation was 1.5 days (range = 1-8 days). All responding patients were on LEV doses >or= 30 mg/kg/day (median 40 mg/kg/day). No significant adverse effects of LEV were reported. LEV may be an effective and safe adjuvant therapy in children with RSE.

  2. Ketogenic diet in 3 cases of childhood refractory status epilepticus.

    PubMed

    Sort, Rune; Born, Alfred P; Pedersen, Karen N; Fonsmark, Lise; Uldall, Peter

    2013-11-01

    Refractory status epilepticus (RSE) in children is associated with a significant risk of death or neurological morbidity. Recently attention has been drawn to the ketogenic diet (KD) as an acute treatment, as it has shown promise in controlling seizures in otherwise refractory status epilepticus in several cases. We have listed these and reviewed all cases of KD used in RSE at our centre. KD was given as 4:1 fat:carbohydrate-protein solution. A 3-year-old girl with RSE due to Hemiconvulsion-Hemiplegia Epilepsy syndrome. KD was instigated on day 6. Seizures stopped with ketosis on day 7. A 10-year-old boy rapidly developing RSE. After months a mitochondrial disorder was discovered. KD was tried twice with severe side-effects but no seizure control. 11-year-old healthy boy with RSE as FIRES. On KD seizures stopped for 24 h one day after reaching ketosis. He improved over 3-4 weeks. KD was efficient in two of three cases of RSE. The non-responder had severe side-effects and proved to have a mitochondrial disorder which is arguably a contraindication for KD. More studies are needed to prove efficacy of KD in RSE, to define optimal timing of KD and possible contraindications for KD in RSE. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  3. Ketogenic diet in pediatric patients with refractory focal status epilepticus.

    PubMed

    Caraballo, Roberto Horacio; Flesler, Santiago; Armeno, Marisa; Fortini, Sebastian; Agustinho, Ariela; Mestre, Graciela; Cresta, Araceli; Buompadre, María Celeste; Escobal, Nidia

    2014-12-01

    The ketogenic diet (KD) has been used as an alternative treatment for patients with refractory status epilepticus (SE). In this retrospective study we assess the efficacy and tolerability of the KD in patients with refractory SE. Between March 1, 2010 and January 1, 2014, 10 patients who met the diagnostic criteria of refractory SE seen at our department were placed on the KD and followed for a minimum of 6 months. Ketonuria was reached within 2-4 days (mean 3 days) for all patients. Seizures stopped in two patients and five patients had a 50-75% seizure reduction within 2-5 days (mean 2.5 days) following the onset of ketonuria and within 5-7 days (mean 5 days) following the onset of the diet. Three patients had a <50% seizure reduction and all of them had severe adverse events so the diet was discontinued. Seven patients remained on the diet for 6 months to 3 years (mean 1.5 years). In all seven patients within 4 months the seizures recurred, but their quality of life did not worsen. The frequency of the seizures consisted of weekly seizures in two, monthly seizures in two, occasional seizures in two, and isolated seizures in one. All of them kept a good tolerability of the diet. The KD is an effective and well-tolerated treatment option for patients with refractory SE. In patients with focal SE secondary to inflammatory or probably inflammatory diseases, the KD should be considered earlier in the course of the treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Pediatric Super-Refractory Status Epilepticus Treated with Allopregnanolone

    PubMed Central

    Broomall, Eileen; Natale, JoAnne E.; Grimason, Michele; Goldstein, Joshua; Smith, Craig M.; Chang, Celia; Kanes, Stephen; Rogawski, Michael A.; Wainwright, Mark S.

    2015-01-01

    Super-refractory status epilepticus is a life-threatening condition. Resistance to benzodiazepine and barbiturate treatment for this disorder is thought to be due to internalization of synaptic γ-aminobutyric acid (GABA)A receptors, and withdrawal of benzodiazepines and barbiturates during treatment often triggers seizure recurrence. The neurosteroid allopregnanolone acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors. Here we describe the use of allopregnanolone in 2 pediatric patients with super-refractory status epilepticus. This treatment allowed the general anesthetic infusions to be weaned with resolution of status epilepticus. This is the first report of allopregnanolone use to treat status epilepticus in children. PMID:25363147

  5. Refractory status epilepticus treated with trigeminal nerve stimulation.

    PubMed

    Moseley, Brian D; Degiorgio, Christopher M

    2014-03-01

    Refractory status epilepticus (RSE) is a neurologic emergency associated with significant morbidity and mortality. Alternative therapies are needed for patients who do not respond to more traditional therapies for RSE. We report on a patient with RSE treated with external trigeminal nerve stimulation (eTNS). On admission, the patient was experiencing consecutive focal dyscognitive seizures with secondary generalization without recovery in between. His seizures remained refractory to multiple therapies, including IV lorazepam, valproic acid, levetiracetam, phenobarbital, and midazolam. Although a burst suppression pattern was achieved with a continuous pentobarbital infusion, seizures returned following attempts to taper it. Given his beneficial response to eTNS during a previous clinical trial, eTNS was initiated. Four days after starting eTNS, the pentobarbital infusion was finally weaned, and his EEG revealed no further seizures. The patient's mental status improved and he was ultimately discharged with only moderately severe disability. Our case demonstrates that eTNS may have antiseizure effects in RSE. Given our patient's quick response, such benefit may have arisen from EEG-desynchronization. If confirmed in larger studies, eTNS could one day be considered along with other adjuvant treatments for RSE.

  6. 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.

  7. Prolonged treatment of refractory status epilepticus in a child.

    PubMed

    Sahin, M; Riviello, J J

    2001-02-01

    Barbiturate anesthesia, which is commonly used for refractory status epilepticus, is an effective treatment, but with many significant complications. The relationship between the duration of this extreme therapy and the ultimate outcome of refractory status epilepticus has not been well studied. We report a 7-year-old girl who presented with refractory status epilepticus secondary to presumed encephalitis with a focal lesion on cranial magnetic resonance imaging. She was treated for 70 days with high-dose antiepileptic drugs and recovered with a residual seizure disorder. This case suggests that, if the status epilepticus is due to a reversible cause such as encephalitis, neurologic recovery may occur despite this very prolonged course of extreme therapy.

  8. Pediatric refractory partial status epilepticus responsive to topiramate.

    PubMed

    Blumkin, Lubov; Lerman-Sagie, Tally; Houri, Tzion; Gilad, Eli; Nissenkorn, Andrea; Ginsberg, Mira; Watemberg, Nathan

    2005-03-01

    Topiramate was safely administered to two young children with refractory partial status epilepticus via nasogastric tube in rapid titration up to a very high total daily dose. An excellent clinical response occurred in both cases. Reaching high daily doses of topiramate within days allowed for safe discontinuation of other antiepileptic drugs in both patients. Given the high efficacy of rapidly titrated topiramate in our patients, this medication may be useful in some cases of pediatric refractory partial status epilepticus. However, more clinical studies on this therapeutic approach are needed to establish the precise role of topiramate in status epilepticus in children.

  9. Refractory status epilepticus due to SMART syndrome.

    PubMed

    Jaraba, Sonia; Puig, Oriol; Miró, Júlia; Velasco, Roser; Castañer, Sara; Rodríguez, Laura; Izquierdo, Cristina; Simó, Marta; Veciana, Misericordia; Falip, Mercè

    2015-08-01

    Stroke-like migraine attacks after radiation therapy (SMART) is a late-onset complication of brain irradiation of unknown physiopathology. Our aim was to present three patients with SMART syndrome who had clinical and neuroimage studies suggestive of status epilepticus. Patient 1. A 69-year-old woman, who was treated with radiation therapy 14 years before her first admission to the Neurology Department, presented with several episodes of headache, speech disturbances, and weakness of left limbs with altered awareness. Patient 2. A 49-year-old man, who was treated with whole brain radiation 20 years before the onset of symptoms, developed some episodes consisting of headache and numbness of the right side of face and right arm; the latest episodes were accompanied by visual disturbances followed by generalized tonic-clonic seizures. Patient 3. A 40-year-old man, who received cranial irradiation 20 years before, suffered three episodes of behavioral disturbance, aphasia, headache, and visual aura followed by left homonymous hemianopia. All three patients suffered seizures mostly with visual aura. Electroencephalography showed interictal epileptiform discharges or focal slowing. Brain magnetic resonance image (MRI), positron emission tomography (PET), or ictal-single-photon emission computed tomography (SPECT) showed focal cortical hyperperfusion. Focal diffusion restriction and focal gadolinium-enhancement were observed on MRI. All patients were treated with antiepileptic drugs, being effective in one of them. One patient needed anesthesic coma, and the other patient responded to therapy with corticosteroids. Taking into account clinical evolution and ictal neuroimaging studies, status epilepticus could explain the origin of these episodes in SMART syndrome. Although most patients have reversible symptoms, in some cases, aggressive treatment to avoid sequelae is needed. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier

  10. Phenotypes of refractory/severe asthma.

    PubMed

    Bush, Andrew; Fleming, Louise

    2011-09-01

    The acid test of phenotyping is that it leads either to a clinically useful or mechanistically important insight. Phenotypes may change over time, but the exact definition of a phenotype shift is unclear. Methods of phenotyping are either investigator driven, in which a priori prejudices are applied to the data, or (semi) objective, in which mathematical techniques or systems biology approaches are applied to the dataset. However, the composition of the dataset is driven by investigator prejudice. Phenotyping is likely most useful in severe asthma, because mild and moderate asthma responds to simple treatments, and no great subtlety is required. Our non-evidence based approach is to define the subpopulation of genuine severe, therapy-resistant asthmatics from the generality of problematic severe asthma. We then investigate them invasively with bronchoscopy and a steroid trial using intramuscular triamcinolone to determine the nature of any inflammatory process; whether inflammation and symptoms are concordant or discordant; whether the inflammatory process is steroid resistant or sensitive; and whether the child has persistent airflow limitation. Other possibly relevant phenotypes include the child with severe exacerbations; brittle asthma; and severe asthma with fungal sensitization. Severe, therapy resistant asthma is a disparate disease, and only international uniform approaches, carefully characterising the children as a prelude to focussed clinical trials will allow progress to be made, and vindicate (or otherwise) our suggested approach.

  11. The outcome of therapies in refractory and super-refractory convulsive status epilepticus and recommendations for therapy.

    PubMed

    Ferlisi, Monica; Shorvon, Simon

    2012-08-01

    In a previous paper, we reviewed the range of therapies available for the treatment of super-refractory status epilepticus. Here we report a review of the outcome of therapies in refractory and super-refractory status epilepticus. Patients (n = 1168) are reported who had therapy with: thiopental, pentobarbital, midazolam, propofol, ketamine, inhalational anaesthetics (isoflurane, desflurane), antiepileptic drugs (topiramate, lacosamide, pregabalin, levetiracetam), hypothermia, magnesium, pyridoxine, immunotherapy, ketogenic diet, emergency neurosurgery, electroconvulsive therapy, cerebrospinal fluid drainage, vagal nerve stimulation and deep brain stimulation. The outcome parameters reported include control of status epilepticus, relapse on withdrawal, breakthrough seizures and mortality. Where reported (596 cases), the long-term outcome was found to be death (35%), severe neurological deficit (13%), mild neurological deficit (13%), undefined deficit (4%) and recovery to baseline (35%). The quality of reported outcome data is generally poor and the number of cases reported for all non-anaesthetic therapies is low. Outcome assessment is complicated by changes in co-medication, delay in response and publication bias. Given these deficits, only broad recommendations can be made regarding optimal therapy. An approach to therapy, divided into first-line, second-line and third-line therapy, is suggested on the basis of this outcome evaluation. The importance of treatments directed at the cause of the status epilepticus, and of supportive ITU care is also emphasized.

  12. Pediatric super-refractory status epilepticus treated with allopregnanolone.

    PubMed

    Broomall, Eileen; Natale, JoAnne E; Grimason, Michele; Goldstein, Joshua; Smith, Craig M; Chang, Celia; Kanes, Stephen; Rogawski, Michael A; Wainwright, Mark S

    2014-12-01

    Super-refractory status epilepticus is a life-threatening condition. Resistance to benzodiazepine and barbiturate treatment for this disorder is thought to be due to internalization of synaptic γ-aminobutyric acid (GABA)A receptors, and withdrawal of benzodiazepines and barbiturates during treatment often triggers seizure recurrence. The neurosteroid allopregnanolone acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors. Here we describe the use of allopregnanolone in 2 pediatric patients with super-refractory status epilepticus. This treatment allowed the general anesthetic infusions to be weaned with resolution of status epilepticus. This is the first report of allopregnanolone use to treat status epilepticus in children. © 2014 American Neurological Association.

  13. Targeted therapeutics for severe refractory asthma: monoclonal antibodies.

    PubMed

    Grainge, Christopher L; Maltby, Steven; Gibson, Peter G; Wark, Peter A B; McDonald, Vanessa M

    2016-07-01

    Severe asthma is a complex multifactorial disease that requires specialist multidisciplinary input for optimal clinical outcomes. Following multidimensional assessment for optimisation of current therapy, self-management skills and comorbidities, all patients should be accurately phenotyped. Only after this assessment has been completed should new monoclonal antibody therapies be considered. In this review, we summarise the new antibody approaches targeting identified pathological pathways in severe refractory asthma.

  14. Neuroprotective effects of deep hypothermia in refractory status epilepticus.

    PubMed

    Niquet, Jerome; Gezalian, Michael; Baldwin, Roger; Wasterlain, Claude G

    2015-12-01

    Pharmacoresistance develops quickly during repetitive seizures, and refractory status epilepticus (RSE) remains a therapeutic challenge. The outcome of RSE is poor, with high mortality and morbidity. New treatments are needed. Deep hypothermia (20°C) is used clinically during reconstructive cardiac surgery and neurosurgery, and has proved safe and effective in those indications. We tested the hypothesis that deep hypothermia reduces RSE and its long-term consequences. We used a model of SE induced by lithium and pilocarpine and refractory to midazolam. Several EEG measures were recorded in both hypothermic (n = 17) and normothermic (n = 20) animals. Neuronal injury (by Fluoro-Jade B), cell-mediated inflammation, and breakdown of the blood-brain barrier (BBB) (by immunohistochemistry) were studied 48 h following SE onset. Normothermic rats in RSE seized for 4.1 ± 1.1 h, and at 48 h they displayed extensive neuronal injury in many brain regions, including hippocampus, dentate gyrus, amygdala, entorhinal and pyriform cortices, thalamus, caudate/putamen, and the frontoparietal neocortex. Deep hypothermia (20°C) of 30 min duration terminated RSE within 12 min of initiation of hypothermia, reduced EEG power and seizure activity upon rewarming, and eliminated SE-induced neuronal injury in most animals. Normothermic rats showed widespread breakdown of the BBB, and extensive macrophage infiltration in areas of neuronal injury, which were completely absent in animals treated with hypothermia. These results suggest that deep hypothermia may open a new therapeutic avenue for the treatment of RSE and for the prevention of its long-term consequences.

  15. 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

  16. 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.

  17. New-onset refractory status epilepticus mimicking herpes virus encephalitis.

    PubMed

    Puoti, Gianfranco; Elefante, Andrea; Saracino, Dario; Capasso, Antonella; Cotrufo, Roberto; Anello, Clara Belluomo

    2013-01-01

    New-onset refractory status epilepticus (NORSE) is a recently defined clinical entity that describes patients who present with status epilepticus of unclear etiology that is highly refractory to therapy. Magnetic resonance imaging (MRI) of NORSE usually discloses no specific abnormalities except for an occasional mild T2/FLAIR hyperintense signal of the mesial temporal lobe. Here, we report a peculiar case of NORSE in which brain MRI showed massive alteration of both temporal lobes, with features strongly supporting the diagnosis of herpes virus encephalitis, but lacking any laboratory evidence of viral infection in the blood and cerebrospinal fluid. It showed also striking signal alterations in the thalamus, which got worse in the course of the disease. This report emphasizes the possibility that seizure activity alone plays a critical role in both determining the disease and whether it will be self-sustaining.

  18. Corpus callosotomy for treatment of pediatric refractory status epilepticus

    PubMed Central

    Greiner, Hansel M.; Tillema, Jan-Mendelt; Hallinan, Barbara E.; Holland, Katherine; Lee, Ki-Hyeong; Crone, Kerry R.

    2012-01-01

    Medically refractory status epilepticus (RSE) causes high morbidity and mortality in children. There are no evidence-based guidelines for treatment. Epilepsy surgery is a treatment option for RSE. We describe a 9-year-old boy treated successfully for RSE with complete corpus callosotomy (CC). Epilepsy surgery should be considered for prolonged RSE. In the absence of evidence of focal epileptogenesis, complete corpus callosotomy may be effective in select cases. PMID:22326839

  19. 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.

  20. Association of seizure duration and outcome in refractory status epilepticus.

    PubMed

    Madžar, Dominik; Geyer, Anna; Knappe, Ruben U; Gollwitzer, Stephanie; Kuramatsu, Joji B; Gerner, Stefan T; Hamer, Hajo M; Huttner, Hagen B

    2016-03-01

    The aim of the study was to identify factors influencing long-term outcome and to evaluate the prognostic power of the Status Epilepticus Severity Score (STESS) in refractory status epilepticus (RSE). We retrospectively extracted data on baseline characteristics, RSE details, and hospital course including complications from all patients treated for RSE in our institution between January 2001 and January 2013. Functional outcome was assessed using the modified Rankin Scale (mRS) and was defined as good when either RSE did not lead to functional decline or when the resulting mRS score was 2 or below. Seventy-one episodes in 65 patients were analyzed. The median follow-up time was 12 weeks (IQR 6-35), two patients were lost to follow-up. Poor functional long-term outcome was observed in 42/69 (60.9%) episodes. In-hospital mortality occurred in 13/71 (18.3%) episodes. Multivariable analysis revealed that STESS ≥ 3, longer RSE duration, and sepsis were independently related to poor functional long-term outcome. Receiver operating characteristics (ROC) curve analyses confirmed the cut-off dichotomization into STESS ≥ 3 and STESS < 3 for optimal discrimination between good and poor outcome (AUC = 0.671, p = 0.002, YI = 0.368, NPV = 0.607, PPV = 0.756) and revealed an RSE duration of 10 days as a significant cut-off point associated with outcome (AUC = 0.712, p = 0.012, YI = 0.310; NPV = 0.545, PPV = 0.750). In conclusion, STESS and RSE duration represent relevant scores and parameters impacting long-term outcome after RSE. A shorter RSE duration is associated with better outcome and, therefore, rapid and adequate treatment for seizure termination should be enforced.

  1. Volatile anesthetic for the control of posthypoxic refractory myoclonic status

    PubMed Central

    Rayadurg, Vivek; Muthuchellappan, Radhakrishnan; Rao, Umamaheshwara

    2016-01-01

    Posthypoxic myoclonus (Lance–Adams syndrome) is characterized by myoclonus involving multiple muscle groups which is resistant to most conventional antiepileptic drugs. We present a case of hypoxic brain injury-induced myoclonic status epilepticus successfully controlled with isoflurane. The antimyoclonic effects of isoflurane are likely due to potentiation of inhibitory postsynaptic GABAA receptor–mediated currents and its effects on thalamocortical pathways. It is effective even when intravenous agents fail to control myoclonus. It may be a useful alternative to intravenous anesthetics as a third tier therapy in patients with refractory status myoclonus. PMID:27630463

  2. Stiripentol for the treatment of super-refractory status epilepticus.

    PubMed

    Strzelczyk, A; Kortland, L-M; Knake, S; Rosenow, F

    2015-12-01

    To determine whether stiripentol (STP) might be a treatment option in super-refractory status epilepticus (SRSE). Medical records of patients treated due to a status epilepticus in Marburg between January 2013 and June 2014 were reviewed for administration of STP. Primary outcome measures were resolution of SE after initiation of STP. Five adult patients were started with STP due to SRSE. The median age was 78 years (interquartile range [IQR] 11 years), and four patients were female. The median duration of SRSE before initiation of STP was 39 days (IQR 16 days), and the median number of anticonvulsants used before was 6 (IQR 1). SRSE ceased in three patients within 2-4 days after the start of STP. In two patients, SRSE continued after administration of STP and further escalation of anticonvulsant regimen. Both were switched eventually to supportive care only. None serious side effects were observed while on STP. Based on our presented cases and previous experimental animal data, STP may prove useful in treating super-refractory SE. Prospective trials are warranted to examine the efficacy of the STP in adults with refractory SE and to examine whether earlier treatment leads to better control of SE. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. 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.

  4. Should Barbiturates be Used in Refractory Status Epilepticus?

    PubMed

    Holtkamp, Martin

    2016-02-01

    Status epilepticus (SE) is a frequent neurologic emergency, one third of patients do not respond to treatment with benzodiazepines followed by a second antiepileptic drug. While initial treatment of complex partial SE is accordant to that of generalized convulsive SE, further management of refractory SE depends on the risk for acute complications and long-term clinical consequences. These risks are low in complex partial SE; therefore, in this clinical form anesthetics commonly are not used. Generalized convulsive SE-even in its early course-is a potentially life-threatening condition; therefore, prompt use of anesthetics is urgently required. Drugs of choice are barbiturates, midazolam, and propofol, all of which exhibit specific advantages and disadvantages. Up to now, data from clinical studies do not allow to prefer or to discard one of these anesthetics, therefore also barbiturates still should be used in refractory SE. A widely accepted in-house protocol for the management of initial and refractory SE is highly recommended.

  5. Super Refractory Status Epilepticus in Hashimoto’s Encephalopathy

    PubMed Central

    Al-Busaidi, Mujahid; Burad, Jyoti; Al-Belushi, Asma; Gujjar, Arun

    2017-01-01

    We present a case of a 38-year-old woman who was at eight weeks of gestation and was admitted to Sultan Qaboos University Hospital with refractory status epilepticus (SE). She presented with a two-day history of fever and a depressed level of consciousness that was followed with generalized tonic-clonic seizures. She progressed to refractory SE that required intubation and mechanical ventilation. Autoimmune workup was suggestive of Hashimoto’s encephalopathy (HE) as suggested by the high levels of thyroid antibodies. Her magnetic resonance imaging showed bilateral hippocampal and basal ganglia hyperintensities, and electroencephalogram showed bilateral frontal epileptiform discharges. Other autoimmune workup was negative. Intravenous anesthetics were started including propofol, midazolam, ketamine, and thiopentone. She was started on multiple immunosuppressive therapies. Multiple antiepileptics were used including phenytoin, lamotrigine, levetiracetam, sodium valproate, clobazam, phenobarbital, and lacosamide. The outcome was unusual in terms of refractoriness to immunotherapy treatment despite a confirmed diagnosis. We did a literature review of all cases with HE presenting with SE with their clinical characteristics and outcome. PMID:28584608

  6. New-Onset Refractory Status Epilepticus: More Investigations, More Questions

    PubMed Central

    Dillien, Philippe; Ferrao Santos, Susana; van Pesch, Vincent; Suin, Vanessa; Lamoral, Sophie; Hantson, Philippe

    2016-01-01

    A 27-year-old previously healthy woman was admitted to the hospital with recurrent seizures. Status epilepticus developed that became refractory to third-line therapy with propofol and barbiturates. The patient had a very extensive diagnostic workup including autoimmune, viral and genetic investigations. A tentative immune therapy was proposed with high doses of steroids and plasma exchanges. Our patient had an inherited heterozygous single nucleotide variant in the sequence c.1280A>G [p.Lys427Arg] of the SMC3 gene that was insufficient to explain the seizures. Surprisingly, IgM antibodies against Japanese encephalitis virus were positive on the serum drawn 11 days after symptom onset, as detected by ELISA and the immunofluorescence antibody (IFA) technique. IgG antibodies were also positive using the IFA technique, but not with ELISA. The same investigations as well as the detection of the viral genome by the q-RT-PCR technique were negative on cerebrospinal fluid. Despite the suspicion of a viral infection, we concluded that our patient had a new-onset refractory status epilepticus of cryptogenic origin. Termination of the status epilepticus was obtained after 47 days, with a possible benefit from the introduction of ketamine. PMID:27462243

  7. Outcome of children with acute encephalitis and refractory status epilepticus.

    PubMed

    Sasaki, Jun; Chegondi, Madhurandhar; Raszynski, Andre; Totapally, Balagangadhar R

    2014-12-01

    Acute encephalitis in children is a life-threatening neurological emergency. However, little is reported about the outcome of this devastating illness in the United States. The authors retrospectively reviewed the charts of patients admitted to a regional pediatric intensive care unit with the diagnosis of acute encephalitis between 2006 and 2011. In 41 cases that met the inclusion criteria, the most common presenting symptoms were fever (65.9%), altered mental status (61%), and seizures (58.5%). Eight patients (19.5%) who presented with refractory status epilepticus had a longer median length of stay in the pediatric intensive care unit (46 vs. 4 days; P < .0001) and a significant worsening of Pediatric Cerebral Performance Category score on discharge by 2 or more points (odds ratio 20.38; 95% confidence interval, 2.89-143.52). All children survived to hospital discharge. In conclusion, children with acute encephalitis who present with refractory status epilepticus have a worse neurological outcome and a longer stay in the pediatric intensive care unit. © The Author(s) 2014.

  8. Refractory ascites - a rare presentation of severe aortic regurgitation.

    PubMed

    Jenkinson, Charles; Rajaratnam, Shanker; Joshi, Pragnesh; Passage, Jurgen

    2014-01-01

    A 47 year-old male with a history of refractory ascites presented to our centre complaining of dyspnoea, abdominal distention, and weight gain. He was admitted under a medical team for investigation and management. Work-up excluded all common aetiologies of ascites. Echocardiography revealed severe aortic regurgitation (AR) with a dilated left ventricle but no right heart pathology or pulmonary hypertension. He underwent mechanical aortic valve replacement. Intra-operatively, a prolapsing left coronary leaflet of the aortic valve with frayed edges raised suspicion of resolved infective endocarditis. Postoperative course was uneventful. Following replacement of the aortic valve, the patient was completely free of ascites. This case demonstrates that ascites can be an unusual clinical presentation of severe aortic regurgitation, which may respond to aortic valve replacement. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  9. Centromedian thalamic nuclei deep brain stimulation in refractory status epilepticus.

    PubMed

    Valentín, Antonio; Nguyen, Huy Q; Skupenova, Alena M; Agirre-Arrizubieta, Zaloa; Jewell, Sharon; Mullatti, Nandini; Moran, Nicholas F; Richardson, Mark P; Selway, Richard P; Alarcón, Gonzalo

    2012-10-01

    Refractory status epilepticus (RSE) is associated with high mortality. We report a potential treatment alternative. Deep brain stimulation (DBS) of the centromedian thalamic nuclei (CMN) can be effective in the treatment of RSE. Report of the evolution of RSE after DBS of the CMN in a 27-year-old man. In the course of an encephalopathy of unknown origin, and after a cardiac arrest, the patient developed RSE with myoclonic jerks and generalized tonic-clonic seizures. The EEG showed continuous generalized periodic epileptiform discharges (GPEDS). Five weeks after RSE onset, bilateral DBS of the CMN was started. This treatment was immediately followed by disappearance of tonic-clonic seizures and GPEDS, suggesting a resolution of RSE. The patient continued having multifocal myoclonic jerks, probably subcortical in origin, which resolved after 4 weeks. The patient remained clinically stable for 2 months in a persistent vegetative state. The remission of RSE, the abolition of GPEDS, and the patient survival suggest that DBS of the CMN may be efficacious in the treatment of refractory, generalized status epilepticus. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. [Super-refractory status epilepticus: treatment with ketogenic diet in pediatrics].

    PubMed

    Vaccarezza, María; Silva, Walter; Maxit, Clarisa; Agosta, Guillermo

    2012-07-01

    Super-refractory status epilepticus is that which persists despite suitable treatment with multiple anti-convulsive schemes, including prolonged coma with general anaesthetic. Different pharmacological treatment schemes have been proposed in these patients, including the use of a ketogenic diet. This study is a retrospective analysis of five patient records of children between 1 and 14 years of age, three of whom were diagnosed with FIRES (febrile infection-related epilepsy syndrome) and two with a diagnosis of refractory symptomatic partial epilepsy. The mean age was six years and the mean duration of the status epilepticus was 32 days. All the patients were given multiple therapeutic schemes; in all was obtained pharmacological coma with barbiturates to reach paroxysm-suppression pattern on electroencephalogram. Since the results of these strategies were not successful, a classical ketogenic diet was indicated. After starting the ketogenic diet, the clinical and electroencephalographic status epilepticus ceased in four patients with good tolerance. One patient did not respond and died. In patients with super-refractory status epilepticus, when different anticonvulsive schemes are unsuccessful, the ketogenic diet would be a good option. The ketogenic diet in this severe clinical situation is highly effective and safe.

  11. Treatment of severe, refractory and rapidly evolving thrombotic thrombocytopenic purpura.

    PubMed

    Acedillo, Rey R; Govind, Mayur; Kashgary, Abdullah; Clark, William F

    2016-06-09

    A 36-year-old man presented to hospital with gross haematuria and evidence of severe, refractory thrombotic thrombocytopenic purpura. Initial treatment with high-volume plasma exchange therapy and early administration of rituximab failed to achieve a sustained clinical response. His clinical course was complicated by left hemianopsia and despite an urgent splenectomy he developed a large right-sided stroke with malignant cerebral oedema that required an emergent decompressive craniotomy. He also had numerous infectious complications as a consequence of an aggressive immunosuppressive strategy. While the patient did not respond to cyclophosphamide, cyclosporine, N-acetylcysteine, and one course of bortezomib, he eventually responded to a second course of bortezomib. One year later, the patient remains in remission and maintains excellent cognitive function. However, he has not completely recovered from his stroke and continues to participate in rehabilitation for his residual physical deficits. 2016 BMJ Publishing Group Ltd.

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

    PubMed Central

    Vyas, Devashish Dhiren; Dash, Gopal Krishna

    2016-01-01

    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. PMID:27390680

  13. Very high dose phenobarbital for refractory status epilepticus.

    PubMed

    Tiamkao, Somsak; Mayurasakorn, Nattakarn; Suko, Panit; Jitpimolmard, Suthipun; Arunpongpaisal, Suwanna; Phuttharak, Warinthorn; Auevitchayapat, Narong; Vannaprasaht, Suda; Tiamkao, Siriporn; Phunikhom, Kutcharin; Chaiyakum, Aporanee; Saengsuwan, Jiamjit

    2007-12-01

    Refractory status epilepticus (RSE), defined as status epilepticus that fails to respond to first, second and third-line therapy. The RSE is associated with high morbidity and mortality. Treatment guidelines of RSE give a spectrum of options, such as, continuous intravenous (i.v.) midazolam (MDL), or continuous i.v. propofol (PRO) as alternatives to phenobarbital (PB) or continuous i.v. pentobarbital (PTB). To study the efficacy of very-high-dose phenobarbital (VHDPB) for treatment RSE. Retrospective study The authors collected and analyzed data from adult patients who were diagnosed with RSE. The authors present 10 patients with RSE who were treated with VHDPB. All of them were generalized convulsive status epilepticus (GCSE). Ages ranged from 16-86 years old (mean.: 43 years). PB dosage ranged 40-140 mg/kg/day (mean: 70 mg/kg/day). The duration of status epilepticus (SE) varied widely, ranged 1-44 days (mean: 7 days). PB level ranged 35.29-218.34 ug/mL (mean 88.1 ug/mL). RSE was controlled by VHDPB 70%, 30% were not controlled. VHDPB were considered as alternative treatment for RSE.

  14. 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.

  15. Propylene Glycol Toxicity in Adolescent with Refractory Myoclonic Status Epilepticus

    PubMed Central

    Cannon, Bryan C.; Ritter, Matthew J.; Schueler, Kerry E.

    2017-01-01

    Propylene glycol (PG) is a solvent commonly used in medications that, while benign at low doses, may cause toxicity in adults and children at high doses. We describe a case and the physiologic sequelae of propylene glycol toxicity manifested in a critically ill adolescent male with refractory myoclonic status epilepticus aggressively treated with multiple PG-containing medications (lorazepam, phenobarbital, and pentobarbital)—all within accepted dosing guidelines and a total daily PG exposure previously recognized to be safe. Hemodynamic measurements by bedside echocardiography during clinical toxicity are also reported. Clinicians should have a high index of suspicion for propylene glycol toxicity in patients treated with PG-containing medications even when the total PG exposure is lower than currently accepted limits. PMID:28331645

  16. (S)-Ketamine in Refractory and Super-Refractory Status Epilepticus: A Retrospective Study.

    PubMed

    Höfler, Julia; Rohracher, Alexandra; Kalss, Gudrun; Zimmermann, Georg; Dobesberger, Judith; Pilz, Georg; Leitinger, Markus; Kuchukhidze, Giorgi; Butz, Kevin; Taylor, Alexandra; Novak, Helmut; Trinka, Eugen

    2016-09-01

    The aim was to describe the safety and efficacy of (S)-ketamine [(S)-KET] in a series of patients with refractory and super-refractory status epilepticus (RSE and SRSE) in a specialized neurological intensive care unit (NICU). We retrospectively analyzed the data of patients with RSE and SRSE treated with (S)-KET in the NICU, Salzburg, Austria, from 2011 to 2015. Data collection included demographic features, clinical presentation, diagnosis, electroencephalogram (EEG) data, anticonvulsant treatment, timing, and duration of treatment with (S)-KET. Outcomes were seizure control and death. A total of 42 patients (14 women) with RSE and SRSE were treated with (S)-KET. The median duration of status epilepticus (SE) was 10 days [first quartile (Q1) 5.0, Q3 21.0]; the median latency from SE onset to the first administration of (S)-KET was 3 days (Q1 2.0, Q3 6.8). Prior to (S)-KET administration, patients had received a median of two (Q1 2.0, Q3 3.0) anesthetics and three (Q1 2.0, Q3 4.0) antiepileptic drugs. Forty percent of patients (17/42) received propofol: 65 % prior to (S)-KET; 35 % at the same time with (S)-KET. Seven patients received a median bolus of (S)-KET of 200 mg (Q1 200, Q3 250) followed by a continuous infusion, while 35 started with a continuous infusion (maximum rate median 2.55 mg/kg/h; Q1 2.09, Q3 3.22). In 64 % of patients (27/42), (S)-KET was the last drug before SE cessation; in five patients, it was given with propofol at the same time. Median duration of administration was 4 days (Q1 2.0, Q3 6.8). Overall (S)-KET treatment was well tolerated, adverse effects were not observed, and overall mortality was 45.2 %. Treatment of SRSE in adult patients with (S)-KET led to resolution of status in 64 %. No adverse events were found, indicating a favorable safety profile.

  17. Refractory anemia with severe dysplasia: clinical significance of morphological features in refractory anemia.

    PubMed

    Matsuda, A; Jinnai, I; Yagasaki, F; Kusumoto, S; Minamihisamatsu, M; Honda, S; Murohashi, I; Bessho, M; Hirashima, K

    1998-04-01

    Refractory anemia (RA) in myelodysplastic syndromes (MDS) are very heterogeneous diseases regarding their morphology, clinical features and survival. We proposed the new designations 'RA with severe dysplasia (RASD)' and 'RA with minimal dysplasia (RAminiD)'. In our criteria, RASD is considered present if a bone marrow (BM) examination shows Pseudo-Pelger-Huet anomalies of mature neutrophils > or =3% and/or micromegakaryocytes (mMgk) of megakaryocytes > or =10% in RA patients. RAminiD is defined as RA cases other than RASD. After the reclassification of 58 primary RA patients, the group was composed of 45 RAminiD and 13 RASD patients. The blast percentage in the BM and the frequency of cytogenetic abnormalities observed in the RASD patients were intermediate between those in the RAminiD and RAEB patients. The analysis of survival curves revealed differences among the three groups; the RASD patients had lower survival probabilities than those of the RAminiD group, and significantly higher probabilities than those of the RAEB group. (RAminiD vs RASD, P=0.06; RASD vs RAEB, P=0.004.) Our data indicate that in RA patients, RASD is a distinct subset of RA with an unfavorable clinical outcome.

  18. Successful treatment of severe refractory lupus hepatitis with mycophenolate mofetil.

    PubMed

    Tagawa, Y; Saito, T; Takada, K; Kawahata, K; Kohsaka, H

    2016-04-01

    Systemic lupus erythematosus-related hepatitis, known as lupus hepatitis, is a rare manifestation of systemic lupus erythematosus, and is usually subclinical with mild abnormalities of serum liver enzymes. While cases with clinically significant and refractory lupus hepatitis are uncommon, treatment options for lupus hepatitis are to be established. Here, we report the case of a 45-year-old man with progressive lupus hepatitis accompanied by autoimmune haemolytic anaemia. Lupus hepatitis of this patient was refractory to tacrolimus, azathioprine and cyclophosphamide, but was successfully treated by mycophenolate mofetil. Mycophenolate mofetil might be an effective therapeutic option for refractory lupus hepatitis.

  19. EEG Characteristics of Successful Burst Suppression for Refractory Status Epilepticus.

    PubMed

    Johnson, Emily L; Martinez, Nirma Carballido; Ritzl, Eva K

    2016-12-01

    Refractory status epilepticus (RSE) is often treated with continuous intravenous medications with the goal of EEG burst suppression. Standard advice is to titrate medications to at least 10-s interburst intervals; however, this has not been shown to improve outcome. We examined EEG characteristics in patients treated with IV anesthetic therapy (IVAT) for RSE to determine which EEG characteristics were associated with successful lifting of IVAT (i.e., without recurrence of status epilepticus). We screened the clinical continuous EEG database for adult patients treated with IVAT for RSE (excluding patients with anoxic injury). We measured the length of bursts and interburst intervals for each patient, calculated EEG burst suppression ratios, and graded bursts for the amount of epileptiform activity. We compared these characteristics in successful versus unsuccessful IVAT lifting attempts. We included 17 successful and 20 unsuccessful lifting attempts in 19 patients (5 used as a holdout validation set). The interburst intervals, burst suppression ratios, and length of bursts did not differentiate successful and unsuccessful lifting attempts; the amount of epileptiform activity in bursts correlated with success or failure to wean IVAT (p = 0.008). Maximum burst amplitude <125 μV had 84.6 % sensitivity and 61.1 % specificity for predicting successful lifting. The length of interburst intervals and burst suppression did not predict successful termination of RSE in this small cohort. This may suggest that EEG characteristics, rather a strict interburst interval goal, could guide IVAT for RSE.

  20. Acute Resective Surgery for the Treatment of Refractory Status Epilepticus.

    PubMed

    Basha, Maysaa Merhi; Suchdev, Kushak; Dhakar, Monica; Kupsky, William J; Mittal, Sandeep; Shah, Aashit K

    2017-03-29

    To identify the role of acute surgical intervention in the treatment of refractory status epilepticus (RSE). Retrospective review of consecutive patients who underwent epilepsy surgery from 2006 to 2015 was done to identify cases where acute surgical intervention was employed for the treatment of RSE. In addition, the adult and pediatric RSE literature was reviewed for reports of surgical treatment of RSE. Nine patients, aged 20-68 years, with various etiologies were identified to have undergone acute surgical resection for the treatment of RSE, aided by electrocorticography. Patients required aggressive medical therapy with antiepileptic drugs and intravenous anesthetic drugs for 10-54 days and underwent extensive neurodiagnostic testing prior to resective surgery. Eight out of nine patients survived and five patients were seizure-free at the last follow-up. The literature revealed 13 adult and 48 pediatric cases where adequate historical detail was available for review and comparison. We present the largest cohort of consecutive adult patients who underwent resective surgery in the setting of RSE. We also reveal that surgery can be efficacious in aborting status and in some can lead to long-term seizure freedom. Acute surgical intervention is a viable option in prolonged RSE and proper evaluation for such intervention should be conducted, although the timing and type of surgical intervention remain poorly defined.

  1. 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.

  2. Successful ECT treatment for medically refractory nonconvulsive status epilepticus in pediatric patient.

    PubMed

    Shin, Hae W; O'Donovan, Cormac A; Boggs, Jane G; Grefe, Annette; Harper, Amy; Bell, William L; McCall, W Vaughn; Rosenquist, Peter

    2011-06-01

    Status epilepticus is a life threatening condition with a high mortality rate in spite of aggressive treatment. There is little consensus on third and fourth line approaches in refractory cases. While electroconvulsive therapy (ECT) has been employed successfully as a treatment for refractory epilepsy and status epilepticus (SE) after exhausting conventional therapy, its use for pediatric patients is limited. We describe a 7-year-old pediatric case in which ECT was used successfully to treat medically refractory nonconvulsive status epilepticus (NCSE) without complete withdrawal of antiepileptic drugs (AED). Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  3. Therapeutic plasma exchange for malignant refractory status epilepticus: a case report.

    PubMed

    Gedik, Ahmet H; Demirkol, Demet; Tatlı, Burak; Bayraktar, Suleyman; Alkan, Alpay; Karabocuoglu, Metin; Yuksel, Adnan

    2014-04-01

    Refractory status epilepticus is a prolongation of status epilepticus despite anticonvulsant therapy with two or three medications in proper doses; it is defined as malignant status epilepticus if it takes weeks or months. Intravenous immunoglobulin, high-dose steroids, magnesium infusion, pyridoxine, hypothermia, ketogenic diet, electroconvulsive therapy, and surgical therapy are the other treatment options for status epilepticus. Our 5-year-old male patient was hospitalized at our pediatric intensive care unit because of status epilepticus secondary to meningoencephalitis. No response could be obtained with many medical and nonmedical therapies in our patient, who developed malignant status epilepticus with unknown etiology. Therapeutic plasma exchange was applied as convulsions continued. Ours is the first child for whom therapeutic plasma exchange was successfully applied because of malignant refractory status epilepticus secondary to meningoencephalitis. Therapeutic plasma exchange may be a treatment option for children with refractory status epilepticus following presumed meningoencephalitis. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. [Use of midazolam for refractory status epilepticus in children].

    PubMed

    Lampin, M-E; Dorkenoo, A; Lamblin, M-D; Botte, A; Leclerc, F; Auvin, S

    2010-01-01

    Morbidity and mortality are high in children with refractory status epilepticus (RSE). Here, we assess the efficacy of midazolam for RSE in children. This was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008. The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failure. We recorded 29 patients with RSE during the study period: 26 were treated with midazolam, including two where midazolam replaced thiopenthal because of hypotension. Midazolam successfully controlled RSE in 58% of patients. Mean delay to cessation of RSE was 48+/-65 minutes. Hypotension was observed in 8% of midazolam-treated patients and 71% of thiopenthal-treated patients. Overall mortality was 15% (4/26). Two deaths occurred long after the cessation of RSE. None of the deaths occurred in midazolam-treated patients. Midazolam is an efficient treatment for RSE in children. Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE.

  5. Assessing the value of topiramate in refractory status epilepticus.

    PubMed

    Madžar, Dominik; Kuramatsu, Joji B; Gerner, Stefan T; Huttner, Hagen B

    2016-05-01

    The aim of this study was to assess factors associated with the use of topiramate (TPM) in refractory status epilepticus (RSE). We retrospectively reviewed RSE episodes over a 12-year period. Episodes treated with and without TPM were compared in terms of demographics, RSE characteristics, clinical course, and outcome in univariate and multivariate analyses. Subgroups defined by type of RSE were studied separately. Functional outcome was assessed with the modified Rankin Scale. Among 71 episodes, 17 (23.9%) were treated with TPM and seizure control was achieved in all of these. The results of unadjusted comparisons suggested a use of TPM in younger and healthier patients who received more perseverant treatment indicated by a higher number of antiepileptic drugs applied. In multivariate analysis adjusting for RSE duration, however, these associations lost significance. Furthermore, TPM was not a predictor of successful RSE termination in neither the overall cohort, nor in the subgroup of complex-partial RSE. After multivariate adjustment, no significant differences were observed between episodes treated with and without TPM in baseline characteristics, treatment, and outcome. Regarding the latter, this study does therefore not yield evidence for a particular efficacy of TPM in RSE. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  6. Ketamine use in the treatment of refractory status epilepticus.

    PubMed

    Synowiec, Andrea S; Singh, Deepinder S; Yenugadhati, Vamsi; Valeriano, James P; Schramke, Carol J; Kelly, Kevin M

    2013-07-01

    Refractory status epilepticus (RSE) occurs when status epilepticus (SE) fails to respond to appropriate therapy with typical antiepileptic drugs (AEDs). Animal studies have shown ketamine to be a highly efficacious agent in this setting, but very few case reports describe use of ketamine in human SE or RSE. We report a retrospective review of 11 patients who were treated for RSE with ketamine infusion in addition to other standard AEDs over a nine-year period. Data collection included age, gender, history of epilepsy, etiology of RSE, daily dose of ketamine, co-therapeutic agents, duration of seizures, treatment response, and disposition. RSE was successfully terminated in all 11 patients treated with ketamine. Dosing ranged from 0.45 mg/kg/h to 2.1 mg/kg/h based upon the preference of the treating clinician and response to therapy, with maximal daily doses ranging from 1392 mg to 4200 mg. Ketamine was the last AED used prior to resolution of RSE in 7/11 (64%) cases. In the remaining four cases, one other AED was added after ketamine infusion had begun. Time from ketamine initiation to seizure cessation ranged from 4 to 28 days (mean=9.8, SD=8.9). In 7/11 patients, RSE was resolved within one week of starting therapy. Administration of ketamine was uniformly associated with improvement in hemodynamic stability. Six of the seven patients (85%) who required vasopressors during early treatment for RSE were able to be weaned from vasopressors during ketamine infusion. No acute adverse effects were noted. These findings suggest that ketamine may be a safe and efficacious adjunctive agent in the treatment of RSE. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Successful rescue of refractory, severe antibody mediated rejection with splenectomy.

    PubMed

    Kaplan, Bruce; Gangemi, Antonio; Thielke, James; Oberholzer, José; Sankary, Howard; Benedetti, Enrico

    2007-01-15

    Antibody-mediated rejection (AMR) commonly occurs after transplantation of ABO-incompatible and sensitized renal transplant. Treatment regimens commonly include a combination of plasmapheresis (PL) and intravenous immunoglobulin (IVIG). However, some cases of AMR remain refractory to treatment. We report a case series of four patients with AMR refractory to standard therapy (ST) who resolved after splenectomy. Four living donor kidney transplant recipients were diagnosed with AMR. Two patients were ABO incompatible, one was cross-match positive and one had no obvious predisposing factors. After failure of therapy with corticosteroids, PL, IVIG, Thymoglobulin, and Rituximab (three patients) or Campath (one patient), AMR was treated with laparoscopic splenectomy. After an average of 11 days of ST, laparoscopic splenectomy was performed for rescue. The urinary output improved immediately in all patients, serum creatinine levels decreased within 48 hr, and ABO titers fell in the ABO-incompatible patient and the cross-match became negative in the two sensitized patients. Splenectomy may play a role in the treatment of AMR refractory to ST.

  8. Effects of clobazam for treatment of refractory status epilepticus.

    PubMed

    Madžar, Dominik; Geyer, Anna; Knappe, Ruben U; Gollwitzer, Stephanie; Kuramatsu, Joji B; Gerner, Stefan T; Hamer, Hajo M; Huttner, Hagen B

    2016-10-21

    Clobazam (CLB) is a well characterized antiepileptic drug (AED) that differs from other benzodiazepines by its basic chemical structure and pharmacodynamic properties. Only one previous study examined the efficacy of CLB as add-on therapy in refractory status epilepticus (RSE). We analyzed RSE episodes treated in our institution between 2001 and 2012. Successful treatment with CLB was scored if CLB was the last AED added to therapy before RSE termination. We assessed the differences between patients with and without CLB and correlated CLB with outcome. Among patients treated with CLB, we studied responders and non-responders and compared our CLB cohort with recently published data. CLB was part of the AED regimen in 24/70 (34.3 %) RSE episodes. In six of these (25.0 %) RSE resolution was attributed to CLB. Baseline characteristics of episodes with and without CLB treatment showed no significant differences and RSE termination rates were very similar (83.3 % vs. 80.4 %). CLB was administered in clinically more complex RSE with longer RSE duration and worse outcome, but CLB was not related independently to outcome. Comparison of our results with previously published data revealed that baseline characteristics as well as CLB maintenance doses and time of treatment initiation were similar in both cohorts. CLB was less frequently the last AED added to RSE therapy in our patients indicating a lower treatment success rate than previously reported. CLB represents a reasonable AED and promising add-on agent for treatment of RSE. However, rates of successful CLB response were substantially lower than in a recently published study. Differing RSE characteristics and treatment strategies may account for the discrepancy between study results, as RSE etiologies and seizures types associated with unfavorable prognosis were more common in our cohort, while anesthetics tended to be less frequently applied to achieve seizure control.

  9. Refractory alloy performance: unresolved issues and status summary

    SciTech Connect

    Harms, W.O.

    1985-01-01

    Viewgraphs are included concerning the research work performed at ORNL on refractory alloys to be used in the SP-100 reactor design concepts. Mechanical properties and irradiation testing of the alloys are described.

  10. 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.

  11. Successful management of super-refractory status epilepticus with thalamic deep brain stimulation.

    PubMed

    Lehtimäki, Kai; Långsjö, Jaakko W; Ollikainen, Jyrki; Heinonen, Hanna; Möttönen, Timo; Tähtinen, Timo; Haapasalo, Joonas; Tenhunen, Jyrki; Katisko, Jani; Öhman, Juha; Peltola, Jukka

    2017-01-01

    Super-refractory status epilepticus is a condition characterized by recurrence of status epilepticus despite use of deep general anesthesia, and it has high morbidity and mortality rates. We report a case of a 17-year-old boy with a prolonged super-refractory status epilepticus that eventually resolved after commencing deep brain stimulation of the centromedian nucleus of the thalamus. Later attempt to reduce stimulation parameters resulted in immediate relapse of status epilepticus, suggesting a pivotal role of deep brain stimulation in the treatment response. Deep brain stimulation may be a treatment option in super-refractory status epilepticus when other treatment options have failed. ANN NEUROL 2017;81:142-146. © 2016 American Neurological Association.

  12. 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.

  13. PD-L1 Status in Refractory Lymphomas

    PubMed Central

    Ghosh, Nilanjan; Kimbrough, Jeffery; Bilalovic, Nurija; Bender, Ryan; Arguello, David; Veloso, Yvonne; Dizdarevic, Aida; Gatalica, Zoran

    2016-01-01

    Targeted immunotherapy based on PD-1/PD-L1 suppression has revolutionized the treatment of various solid tumors. A remarkable improvement has also been observed in the treatment of patients with refractory/relapsing classical Hodgkin lymphoma (cHL). We investigated PD-L1 status in a variety of treatment resistant lymphomas. Tumor samples from 78 patients with therapy resistant lymphomas were immunohistochemically (IHC) investigated for the expression of PD-L1 using two antibody clones (SP142 and SP263, Ventana). Thirteen PD-L1+ cases were further analyzed for gene copy number variations (CNV) by NGS and for PD-L1/JAK2/PD-L2 co-amplification using fluorescent in-situ hybridization assay (FISH). PD-L1 positivity (≥5% positive cancer cells, IHC) was present in 32/77 (42%) and 33/71 cases (46%) using SP142 and SP263 antibodies, respectively. Concordance between the two anti-PD-L1 clones was high with only three (4%) discrepant cases. The strongest and consistent (10/11 cases) expression was observed in cHL and primary mediastinal B-cell lymphomas (3/3). Diffuse large B-cell lymphomas (DLBCL) were frequently positive (13/26) irrespective of subtype. Follicular (1/8), peripheral T-cell (3/11) and mantle cell (1/8) lymphomas were rarely positive, while small lymphocytic lymphoma/CLL and marginal zone lymphomas were consistently negative (3/3). Co-amplification/CNVs of PD-L1/JAK2/PD-L2 were observed in 3 cases of DLBCL and cHL, respectively. Of note, all three cHL-amplified cases were positive by FISH, but not by NGS. Since only a fraction of the IHC positive lymphoma cases were positive by FISH and NGS assays, other mechanisms are involved in PD-L1 upregulation, especially in DLBCL. FISH assay may be more suitable than NGS assay for determination of PD-L1 alterations in cHL. PMID:27861596

  14. Progressive Brain Atrophy in Super-refractory Status Epilepticus.

    PubMed

    Hocker, Sara; Nagarajan, Elanagan; Rabinstein, Alejandro A; Hanson, Dennis; Britton, Jeffrey W

    2016-10-01

    Prolonged seizures in super-refractory status epilepticus (SRSE) have been shown to cause neuronal death and reorganization, and visual inspection in individual case studies has demonstrated progressive cortical and subcortical atrophy. At present, magnetic resonance imaging (MRI) studies that evaluate brain atrophy in SRSE are lacking. To document and quantify the development of atrophy over time in SRSE. This retrospective medical record review included all patients with SRSE who were admitted to a tertiary referral campus of the Mayo Clinic Hospital with SRSE from January 1, 2001, to December 31, 2013. Patients with (1) an initial MRI scan performed within 2 weeks of SRSE onset, (2) a second MRI scan within 6 months of SRSE resolution, and (3) a minimum duration of 1 week between MRI scans were included. The ventricular brain ratio (VBR) was measured on T2-weighted fluid-attenuated inversion recovery (FLAIR) images at disease onset and during follow-up. Measurements were performed on axial FLAIR images with section thickness of less than 5 mm. The plane immediately superior to the caudate head was chosen for analysis. The hypothesis that atrophy develops during SRSE despite seizure control (electroencephalogram background suppression with anesthetic drugs) was tested. Data were analyzed from June 1 to December 31, 2015. Change in VBR (ΔVBR) as a percentage of the starting measure. Nineteen patients met the inclusion criteria; these included 10 men (53%) and 9 women (47%) with a median age of 41 (interquartile range [IQR], 25-68) years. Anesthetic agents were required for a median of 13 (IQR, 5-37) days. Initial MRI was performed a median of 2 (IQR, 1-7.5) days from the onset of SRSE, and the second MRI was performed a median of 11 (IQR, 5-15.5) days from the resolution of SRSE, with a median of 40 (IQR, 15-65) days between MRI scans. Median ΔVBR was 23.3% (IQR, 10.5%-70.3%). A significant correlation between the duration of anesthetic agent use and ΔVBR was

  15. Propofol treatment in adult refractory status epilepticus. Mortality risk and outcome.

    PubMed

    Power, Kjersti Nesheim; Flaatten, Hans; Gilhus, Nils Erik; Engelsen, Bernt A

    2011-03-01

    To retrospectively study effect and safety of propofol treatment in adult refractory generalised tonic clonic status epilepticus. Therapy refractory status epilepticus (RSE) is defined as a status that does not respond to 1st or 2nd line of treatment. Different anaesthetics are used to treat RSE, but no definite recommendations or priority has been scientifically established. Propofol has been the preferred agent for treating RSE at our intensive care unit since 2001. We present treatment mode, effect and outcome in 18 patients with 27 consecutive cases of RSE treated 2001-2010. Fifteen patients had 1 episode, and 3 patients had 2, 3 and 7 episodes, respectively. Mortality risk for each case of RSE was estimated using the Simplified Acute Physiology (SAPS) II score. Probable trigger factors were identified for 22 of the 27 RSE episodes. In 16/27 episodes seizures lasted more than 2h before anaesthesia was induced. A mean total dose of 7885.1mg was given for a mean duration of 34.4h. Break through seizures occurred in 8 of the patients and in 2 episodes of RSE in one patient, i.e. 9/27 episodes of RSE. Propofol was changed to another anaesthetic agent in 2 episodes. Complications occurred in 17 of the RSE episodes, the most frequent was pneumonia (9/27). One patient had complications that could be related to a propofol infusion syndrome (PRIS). In 8 of 18 patients and 14/27 RSE episodes no sequelae occurred. Seven episodes were associated with mild and 4 with severe sequelae and 2 of the patients died. We found a trend only for SAPS II score being higher in patients with more severe sequelae. Our data support propofol as an effective anaesthetic for treating RSE. Close clinical observation for possible PRIS is warranted if propofol is given for more than 48h. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. A Comparison of Intravenous Levetiracetam and Valproate for the Treatment of Refractory Status Epilepticus in Children.

    PubMed

    İşgüder, Rana; Güzel, Orkide; Ceylan, Gökhan; Yılmaz, Ünsal; Ağın, Hasan

    2016-08-01

    Because of the lack of studies comparing the efficacy and safety of levetiracetam and valproate before the induction of general anesthesia in the treatment of convulsive refractory status epilepticus in children, we aimed to compare the effectiveness of these antiepileptic drugs in patients with convulsive status epilepticus admitted to the Pediatric Intensive Care Unit between 2011 and 2014. Forty-six (59%) of the 78 patients received levetiracetam, and 32 (41%) received valproate for the treatment of refractory status epilepticus. The response rate was not significantly different between the 2 groups. Although no adverse event was noted in patients who received levetiracetam, 4 (12.5%) patients in the valproate group experienced liver dysfunction (P = .025). According to our results, levetiracetam and valproate may be used in the treatment of refractory status epilepticus before the induction of general anesthesia. Levetiracetam appears as effective as valproate, and also safer. © The Author(s) 2016.

  17. High-dose barbiturates for refractory intracranial hypertension in children with severe traumatic brain injury.

    PubMed

    Mellion, Sarah A; Bennett, Kimberly Statler; Ellsworth, German L; Moore, Kevin; Riva-Cambrin, Jay; Metzger, Ryan R; Bratton, Susan L

    2013-03-01

    To evaluate high-dose barbiturates as a second-tier therapy for pediatric refractory intracranial hypertension complicating severe traumatic brain injury. This is a retrospective cohort study of children with refractory intracranial hypertension treated with high-dose barbiturates. A single center level I pediatric trauma from 2001 to 2010. Thirty-six children with refractory intracranial hypertension defined as intracranial pressure greater than 20 mm Hg despite standard management treated with high-dose barbiturates after severe traumatic brain injury. High-dose barbiturates were administered for refractory intracranial hypertension for a minimum duration of 6 hours and monitored by continuous electroencephalography. Exposure was control of refractory intracranial hypertension defined as > 20 mm Hg within 6 hours after starting barbiturates. Pediatric cerebral performance category scores at hospital discharge and at 3 months (or longer) follow-up were the primary outcomes. Ten of 36 patients (28%) had control of refractory intracranial hypertension. Neither demographic nor injury characteristics were associated with refractory intracranial hypertension control. Children who responded received barbiturates significantly later after injury (76 vs. 29 median hours). Overall, 14 children died, 13 without control of intracranial pressure. Survival was more common in those who responded compared with those who did not respond to high-dose barbiturates, although this did not reach statistical significance (relative risk of death 0.2; 95% confidence interval; [0.03-1.3]). Of the 22 survivors, 19 had an acceptable survival (pediatric cerebral performance category less than 3) at 3 months or longer after injury; however, only three returned to normal function. Among survivors, control of refractory intracranial hypertension was associated with significantly better pediatric cerebral performance category scores and over two-fold likelihood of acceptable long-term outcome

  18. 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.

  19. 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.

  20. Evolution of Cerebral Atrophy in a Patient with Super Refractory Status Epilepticus Treated with Barbiturate Coma

    PubMed Central

    George, Pravin; Nattanmai, Premkumar; Ahrens, Christine; Hantus, Stephen; Sarwal, Aarti

    2017-01-01

    Introduction. Status epilepticus is associated with neuronal breakdown. Radiological sequelae of status epilepticus include diffusion weighted abnormalities and T2/FLAIR cortical hyperintensities corresponding to the epileptogenic cortex. However, progressive generalized cerebral atrophy from status epilepticus is underrecognized and may be related to neuronal death. We present here a case of diffuse cerebral atrophy that developed during the course of super refractory status epilepticus management despite prolonged barbiturate coma. Methods. Case report and review of the literature. Case. A 19-year-old male with a prior history of epilepsy presented with focal clonic seizures. His seizures were refractory to multiple anticonvulsants and eventually required pentobarbital coma for 62 days and midazolam coma for 33 days. Serial brain magnetic resonance imaging (MRI) showed development of cerebral atrophy at 31 days after admission to our facility and progression of the atrophy at 136 days after admission. Conclusion. This case highlights the development and progression of generalized cerebral atrophy in super refractory status epilepticus. The cerebral atrophy was noticeable at 31 days after admission at our facility which emphasizes the urgency of definitive treatment in patients who present with super refractory status epilepticus. Further research into direct effects of therapeutic coma is warranted. PMID:28182114

  1. [Cases of non-standard approach to treatment of super-refractory status epilepticus].

    PubMed

    Karlov, V A; Vlasov, P N; Gladov, B P; Kamelkova, E G

    2015-01-01

    Authors assume that super-refractoriness is probably characterized by the specific pathophysiological mechanisms of status epilepticus development and can't be treated using standard treatment schemes. By the example of two clinical cases, we have analyzed the efficacy of complex treatment of super-refractory nonconvulsive and myoclonic status using intravenous valproate, central anesthetics (thiopental sodium, propofol), levetiracetam and cortexin. Preliminary results suggest that cortexin and levetiracetam as add-on to standard treatment may be vitally important drugs for the patients.

  2. Refractory metabolic acidosis as a complication of high-dose midazolam infusion for pediatric status epilepticus.

    PubMed

    Federman, Myke D; Kelly, Robert; Harrison, Rick E

    2009-01-01

    The use of midazolam for the treatment of status epilepticus in children has generally been shown to be well tolerated and safe. Furthermore, encouraging efficacy has been observed when pediatric patients with status epilepticus have received continuous intravenous infusions of midazolam. A 9-year-old girl was treated with high-dose, continuous intravenous infusion of midazolam for the management of refractory status epilepticus. The patient developed a severe hyperchloremic, non-anion gap metabolic acidosis and resultant hemodynamic compromise, necessitating significant inotropic support and the initiation of a vasopressor infusion. We speculate that this complication was due to the preparation of parenteral midazolam with hydrochloric acid. The midazolam infusion was stopped, and, in less than 5 hours, the patient's metabolic acidosis resolved. The patient's inotropic and vasopressor infusions could only be weaned after discontinuing the use of high-dose midazolam. Although this complication was observed in only 1 pediatric patient with cortical dysplasia, caution and close clinical and laboratory surveillance should be exercised when administering continuous intravenous infusions of midazolam to pediatric patients.

  3. Clinical profile and outcome of refractory convulsive status epilepticus in older children from a developing country.

    PubMed

    Lingappa, Lokesh; Konanki, Ramesh; Patel, Ravi; Vooturi, Sudhindra; Jayalakshmi, Sita

    2016-03-01

    The current study evaluates the etiology, clinical course and outcome of refractory convulsive status epilepticus (CSE) in older children. Retrospective analysis of data of 73 children with CSE, aged ≥2 and ≤12 years was performed. Odds ratios were calculated between variables for clinical course and outcome. Mortality of the group was analyzed using survival analysis. Thirty three (45.2%) children progressed to refractory status epilepticus (RSE). The most common etiology for CSE was acute symptomatic in 44 (60.3%) of which 37 had presumed CNS infections. The odds of progressing to RSE were higher in children with acute symptomatic etiology (OR 2.62; CI - 95%; 0.99-7.14; p=0.041). Progression to RSE increased the chances of severe sepsis by six times (OR 6.08; CI - 95%; 1.19-31.02; p=0.036) and acidosis by nearly 15 times (OR 14.77; CI - 95%; 1.19-31.02; p=0.020). Overall mortality was 13.7%, higher in RSE (21.2% vs.7.5%). Amongst the 63 surviving children followed for 1 year from discharge, progression to RSE increased the odds of disability by seven times (OR 7.08; CI 29.31; p=0.004). Acute symptomatic etiology was the commonest cause of CSE among older children from developing country and increased the odds of progressing to RSE. RSE was significantly associated with disability at 1 year from discharge. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  4. Thoracic Sympathectomy for Severe Refractory Multivessel Coronary Artery Spasm.

    PubMed

    Cardona-Guarache, Ricardo; Pozen, Jonah; Jahangiri, Arehzo; Koneru, Jayanthi; Shepard, Richard; Roberts, Charlotte; Abbate, Antonio; Cassano, Anthony

    2016-01-01

    Coronary artery spasm is a rare but potentially fatal disease. Herein, we report a case of recurrent ST-segment myocardial infarctions and ventricular fibrillation complicating severe multivessel coronary artery spasm successfully treated with bilateral thoracic surgical sympathectomy. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed

    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

    2017-05-18

    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 hyperresponsiveness, a physiological marker of severe asthma, as well as on airway mast-cell numbers and activation in patients with severe asthma. 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. 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. 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 others; ClinicalTrials.gov number, NCT

  6. 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.

  7. Propofol Infusion Syndrome in Refractory Status Epilepticus: A Case Report and Topical Review

    PubMed Central

    Dam, Mette

    2016-01-01

    Propofol infusion syndrome (PRIS) is a fatal complication when doses of propofol administration exceed 4 mg/kg/h for more than 48 hours. Propofol overdosage is not uncommon in patients with refractory status epilepticus (RSE). We describe a case of refractory status epilepticus complicated by propofol infusion syndrome and collect from 5 databases all reports of refractory status epilepticus cases that were treated by propofol and developed the syndrome and outline whether refractory status epilepticus treatment with propofol is standardized according to international recommendations, compare it with alternative medications, and discuss how this syndrome can be treated and prevented. A total of 21 patients who developed this syndrome reported arrhythmia in all cases (100%), rhabdomyolysis in 9 cases (42%), lactic acidosis in 13 cases (62%), renal failure in 8 cases (38%), lipemia in 7 cases (33%), and elevated hepatic enzymes in 6 cases (28%). 13 patients died (66%). Propofol is still given in a dosage higher than what is internationally recommended, and new treatment modalities such as renal replacement therapy, blood exchange, and extracorporeal membrane oxygenation seem to be promising. In conclusion, propofol should be carefully titrated, the maximal infusion rate needs to be reassessed, and combination of different sedative agents may be considered. PMID:27493812

  8. Prolonged treatment for acute symptomatic refractory status epilepticus: outcome in children.

    PubMed

    Sahin, Mustafa; Menache, Caroline C; Holmes, Gregory L; Riviello, James J

    2003-08-12

    High-dose suppressive therapy (HDST) is used to treat refractory status epilepticus (RSE). Prolonged therapy is required in some cases, and prognosis is important in making therapeutic decisions. The authors therefore studied the long-term outcome in previously normal children who survived prolonged HDST for acute symptomatic RSE. All have intractable epilepsy, and none returned to baseline.

  9. 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.

  10. Management of refractory status epilepticus in adults: still more questions than answers.

    PubMed

    Rossetti, Andrea O; Lowenstein, Daniel H

    2011-10-01

    Refractory status epilepticus (RSE) is 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 cause (which should be actively targeted). Recent recommendations for adults suggest that the aggressiveness of treatment for RSE should be tailored to the clinical situation. To minimise intensive care unit-related complications, focal RSE without impairment of consciousness might initially be approached conservatively; conversely, early induction of pharmacological coma is advisable in generalised convulsive forms of the disorder. At this stage, midazolam, propofol, or barbiturates are the most commonly used drugs. Several other treatments, such as additional anaesthetics, other antiepileptic or immunomodulatory compounds, or non-pharmacological approaches (eg, electroconvulsive treatment or hypothermia), have been used in protracted RSE. Treatment lasting weeks or months can sometimes result in a good outcome, as in selected patients after encephalitis or autoimmune disorders. Well designed prospective studies of RSE are urgently needed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Nonmyeloablative peripheral blood haploidentical stem cell transplantation for refractory severe aplastic anemia.

    PubMed

    Clay, Jennifer; Kulasekararaj, Austin G; Potter, Victoria; Grimaldi, Francesco; McLornan, Donal; Raj, Kavita; de Lavallade, Hugues; Kenyon, Michelle; Pagliuca, Antonio; Mufti, Ghulam J; Marsh, Judith C W

    2014-11-01

    New transplant approaches are urgently needed for patients with refractory severe aplastic anemia (SAA) who lack a matched sibling or unrelated donor (UD) or who have failed UD or cord blood transplant. Patients with refractory SAA are at risk of later clonal evolution to myelodysplastic syndrome and acute leukemia. We report our pilot findings with haploidentical hematopoietic stem cell transplantation (haploHSCT) using uniform reduced-intensity conditioning with postgraft high-dose cyclophosphamide in 8 patients with refractory SAA or patients who rejected a prior UD or cord blood transplant. Six of 8 patients engrafted. Graft failure was associated with donor-directed HLA antibodies, despite intensive pre-HSCT desensitization with plasma exchange and rituximab. There was only 1 case of grade II skin graft-versus-host disease. We show that haploHSCT can successfully rescue refractory SAA patients who lack donor-directed HLA antibodies but not in the presence of donor-directed HLA antibodies. This novel protocol for haploHSCT for SAA has been adopted by the European Group for Blood and Marrow Transplantation Severe Aplastic Anaemia Working Party for a future noninterventional, observational study to further evaluate its efficacy.

  12. 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.

  13. Isolated fatty liver from prolonged propofol use in a pediatric patient with refractory status epilepticus.

    PubMed

    Rison, Richard A; Ko, David Y

    2009-07-01

    Propofol is a widely used rapidly acting sedating or hypnotic agent in the intensive care setting. It is generally considered safe in both pediatric and adult patients and has been used frequently in cases of refractory status epilepticus. The formulation of propofol is highly lipophilic to facilitate central nervous system penetration and has a high fat content, and prolonged infusions have been known to cause both extrahepatic complications and hepatomegaly secondary to fatty liver. Whereas extrahepatic manifestations of prolonged propofol infusions have been well reported in non-neurologic intensive care patients, cases of pathologically confirmed fatty liver in patients with status epilepticus are relatively few. Furthermore, these cases of hepatomegaly and fatty liver have been also in the context of concomitant extrahepatic side effects. We report on a pediatric patient with refractory status epilepticus treated with a prolonged propofol infusion who developed isolated pathologically confirmed fatty liver without the usually reported extrahepatic manifestations.

  14. 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

  15. Surgical treatment of focal symptomatic refractory status epilepticus with and without invasive EEG.

    PubMed

    Oderiz, Carolina Cuello; Aberastury, Marina; Besocke, Ana Gabriela; Sinner, Jorge; Comas-Guerrero, Betiana; Ciraolo, Carlos Alberto; Pasteris, Maria Concepción; Silva, Walter Horacio; García, María Del Carmen

    2015-01-01

    Neurosurgery appears to be a reasonable alternative in carefully selected patients with refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE). We discuss the optimal timing of the surgery and the use of previous stereoelectroencephalography (SEEG) invasive evaluation. We identified 3 patients (two pediatric and one adult) who underwent epilepsy surgery because of RSE or SRSE from our epilepsy surgery database, one of them with previous SEEG. Status epilepticus resolved acutely in all of them with no mortality and no substantial morbidity. At follow-up (median: 2 years), 1 patient was seizure-free, and 2 had significant improvement. Surgery should be considered in all cases of RSE and SRSE early in the course of the evolution of the disease.

  16. New-onset refractory status epilepticus: Etiology, clinical features, and outcome.

    PubMed

    Gaspard, Nicolas; 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

    2015-11-03

    The aims of this study were to determine the etiology, clinical features, and predictors of outcome of new-onset refractory status epilepticus. 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). 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. 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. © 2015 American Academy of Neurology.

  17. Remission of Severe, Relapsed, and Refractory TTP after Multiple Cycles of Bortezomib

    PubMed Central

    Pandey, Manu R.; Ontiveros, Evelena P.

    2017-01-01

    Acquired thrombotic thrombocytopenic purpura (TTP) is characterized by autoantibodies against a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). Uncleaved von Willebrand factor (VWF) multimers accumulate and bind to platelets which causes spontaneous microthrombi ultimately causing microangiopathic hemolytic anemia, thrombocytopenia, and end-organ ischemia. Plasma exchange (PEX) with or without steroids constitutes standard first-line therapy with rituximab typically reserved for refractory cases. Therapies beyond rituximab lack strong evidence for routine use. Recently, bortezomib, a proteasome inhibitor used commonly in patients with multiple myeloma, was shown to induce remission in patients with refractory TTP. Here, we report a case of severe, relapsed TTP that was refractory to PEX, steroids, and rituximab that underwent remission following three cycles of bortezomib. We discuss the salient features of our case, the mechanism of action of bortezomib, and the very few other similar reports that exist in the literature. We conclude that bortezomib should be considered for patients with TTP refractory to PEX, steroids, and rituximab due to its efficacy and relatively favorable side effect profile. PMID:28367342

  18. 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.

  19. Delirium in advanced age and dementia: A prolonged refractory course of delirium and lower functional status.

    PubMed

    Boettger, Soenke; Jenewein, Josef; Breitbart, William

    2015-08-01

    The factors associated with persistent delirium, in contrast to resolved delirium, have not been studied well. The aim of our present study was to identify the factors associated with delirium resolution as measured by the Memorial Delirium Assessment Scale (MDAS) and functional improvement as measured by the Karnofsky Performance Status (KPS) scale. All subjects were recruited from psychiatric referrals at the Memorial Sloan Kettering Cancer Center (MSKCC). The two study instruments were performed at baseline (T1), at 2-3 days (T2), and at 4-7 days (T3). Subjects with persistent delirium were compared to those with resolved delirium in respect to sociodemographic and medical variables. Overall, 26 out of 111 patients had persistent delirium. These patients were older, predominantly male, and had more frequently preexisting comorbid dementia. Among cancer diagnoses and stage of illness, brain cancer and terminal illness contributed to persistent delirium or late response, whereas gastrointestinal cancer was associated with resolved delirium. Among etiologies, infection responded late to delirium management, usually at one week. Furthermore, delirium was more severe in patients with persistent delirium from baseline through one week. At baseline, MDAS scores were 20.1 in persistent delirium compared to 17 to 18.8 in resolved delirium (T2 and T3), and at one week of management (T3), MDAS scores were 15.2 and 4.7 to 7.4, respectively. At one week of management, persistent delirium manifested in more severe impairment in the domains of consciousness, cognition, organization, perception, psychomotor behavior, and sleep-wake cycle. In addition, persistent delirium caused more severe functional impairment. In this delirium sample, advanced age and preexisting dementia, as well as brain cancer, terminal illness, infection, and delirium severity contributed to persistent delirium or late response, indicating a prolonged and refractory course of delirium, in addition to more

  20. Delirium in advanced age and dementia: A prolonged refractory course of delirium and lower functional status

    PubMed Central

    BOETTGER, SOENKE; JENEWEIN, JOSEF; BREITBART, WILLIAM

    2017-01-01

    Objective The factors associated with persistent delirium, in contrast to resolved delirium, have not been studied well. The aim of our present study was to identify the factors associated with delirium resolution as measured by the Memorial Delirium Assessment Scale (MDAS) and functional improvement as measured by the Karnofsky Performance Status (KPS) scale. Method All subjects were recruited from psychiatric referrals at the Memorial Sloan Kettering Cancer Center (MSKCC). The two study instruments were performed at baseline (T1), at 2–3 days (T2), and at 4–7 days (T3). Subjects with persistent delirium were compared to those with resolved delirium in respect to sociodemographic and medical variables. Results Overall, 26 out of 111 patients had persistent delirium. These patients were older, predominantly male, and had more frequently preexisting comorbid dementia. Among cancer diagnoses and stage of illness, brain cancer and terminal illness contributed to persistent delirium or late response, whereas gastrointestinal cancer was associated with resolved delirium. Among etiologies, infection responded late to delirium management, usually at one week. Furthermore, delirium was more severe in patients with persistent delirium from baseline through one week. At baseline, MDAS scores were 20.1 in persistent delirium compared to 17 to 18.8 in resolved delirium (T2 and T3), and at one week of management (T3), MDAS scores were 15.2 and 4.7 to 7.4, respectively. At one week of management, persistent delirium manifested in more severe impairment in the domains of consciousness, cognition, organization, perception, psychomotor behavior, and sleep–wake cycle. In addition, persistent delirium caused more severe functional impairment. Significance of results In this delirium sample, advanced age and preexisting dementia, as well as brain cancer, terminal illness, infection, and delirium severity contributed to persistent delirium or late response, indicating a prolonged

  1. 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.

  2. Observed medical and surgical complications of prolonged barbiturate coma for refractory status epilepticus

    PubMed Central

    Newey, Christopher R.; Wisco, Dolora; Nattanmai, Premkumar; Sarwal, Aarti

    2016-01-01

    Background: Refractory status epilepticus is often treated with third-line therapy, such as pentobarbital coma. However, its use is limited by side effects. Recognizing and preventing major and minor adverse effects of prolonged pentobarbital coma may increase good outcomes. This study retrospectively reviewed direct and indirect medical and surgical pentobarbital coma. Methods: Retrospective chart review of all patients with refractory status epilepticus treated with pentobarbital over a 1 year period at a large tertiary care center. We collected baseline data, EEG data, and complications that were observed. Results: Overall, nine patients [median age 46.4 (IQR 21.7, 75.5) years] were induced with pentobarbital coma median 11 (IQR 3, 33) days after seizure onset for a median of 9 (IQR 3.5, 45.4) days. A total of four to eight concurrent antiepileptics were tried prior to the pentobarbital coma. Phenobarbital, due to recurrence of seizures on weaning pentobarbital coma, was required in seven patients. Observed complications included peripheral neuropathy (77.8%), cerebral atrophy (33.3%), volume overload (44.4%), renal/metabolic (77.8%), gastrointestinal (66.6%), endocrine (55.6%), cardiac/hemodynamic/vascular (77.8%), respiratory (100%), and infectious (77.8%). The number of complications trended with duration of induced coma but was nonsignificant. Median ICU length of stay was 40 (IQR 28, 97.5) days. Overall, five patients were able to follow commands after a median 37 (IQR 25.5, 90) days from coma onset. There were eight patients that were discharged from hospital with three remaining in a prolonged unresponsive state. There was one patient that died prior to discharge. Conclusions: This study highlights the high morbidity in patients with refractory status epilepticus requiring pentobarbital coma. Anticipating and addressing the indirect and direct complications in prolonged pentobarbital coma may improve survival and functional outcomes in patients with

  3. 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.

  4. 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

  5. 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.

  6. Efficacy of Anti-TNFα in Severe and Refractory Neuro-Behcet Disease

    PubMed Central

    Desbois, Anne Claire; Addimanda, Olga; Bertrand, Anne; Deroux, Alban; Pérard, Laurent; Depaz, Raphael; Hachulla, Eric; Lambert, Marc; Launay, David; Subran, Benjamin; Ackerman, Felix; Mariette, Xavier; Cohen, Fleur; Marie, Isabelle; Salvarini, Carlo; Cacoub, Patrice; Saadoun, David

    2016-01-01

    Abstract To report the safety and efficacy of anti-tumor necrosis factor α (TNFα) therapy in severe and refractory neuro-Behçet disease (NBD) patients. Observational, multicenter study including 17 BD patients (70.6% of male, with a median age of 39.3 [24–60] years), with symptomatic parenchymal NBD, refractory to previous immunosuppressant and treated with anti-TNFα (infliximab 5 mg/kg [n = 13] or adalimumab [n = 4]). Complete remission was defined by the disappearance of all neurological symptoms and by the improvement of radiological abnormalities at 12 months. Overall improvement following anti-TNF was evidenced in 16/17 (94.1%) patients including 6 (35.3%) complete response and 10 (58.8%) partial response. The median time to achieve remission was 3 months (1–6). The median Rankin score was 2 (1–4) at the initiation of anti-TNFα versus 1 (0–4) at the time of remission (P = 0.01). Corticosteroids have been stopped in 4 (23.5%) patients, and reduced by more than 50% as compared with the dosage at baseline in 10 (58.8%) patients. Side effects occurred in 23.5% of patients and required treatment discontinuation in 17% of cases. TNF blockade represents an effective therapeutic approach for patients with severe and refractory NBD, a difficult to treat population. PMID:27281066

  7. Comparison of Intravenous Anesthetic Agents for the Treatment of Refractory Status Epilepticus

    PubMed Central

    Reznik, Michael E.; Berger, Karen; Claassen, Jan

    2016-01-01

    Status epilepticus that cannot be controlled with first- and second-line agents is called refractory status epilepticus (RSE), a condition that is associated with significant morbidity and mortality. Most experts agree that treatment of RSE necessitates the use of continuous infusion intravenous anesthetic drugs such as midazolam, propofol, pentobarbital, thiopental, and ketamine, each of which has its own unique characteristics. This review compares the various anesthetic agents while providing an approach to their use in adult patients, along with possible associated complications. PMID:27213459

  8. Deep brain stimulation for medically refractory life-threatening status dystonicus in children.

    PubMed

    Walcott, Brian P; Nahed, Brian V; Kahle, Kristopher T; Duhaime, Ann-Christine; Sharma, Nutan; Eskandar, Emad N

    2012-01-01

    Generalized dystonic syndromes may escalate into persistent episodes of generalized dystonia known as status dystonicus that can be life-threatening due to dystonia-induced rhabdomyolysis and/or respiratory compromise. Treatment of these conditions usually entails parenteral infusion of antispasmodic agents and sedatives and occasionally necessitates a medically induced coma for symptom control. The authors report a series of 3 children who presented with medically intractable, life-threatening status dystonicus and were successfully treated with bilateral pallidal deep brain stimulation. Bilateral globus pallidus internus stimulation appears to be effective in the urgent treatment of medically refractory and life-threatening movement disorders.

  9. 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.

  10. 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

  11. Activity of alemtuzumab monotherapy in treatment-naive, relapsed, and refractory severe acquired aplastic anemia

    PubMed Central

    Nunez, Olga; Weinstein, Barbara; Scheinberg, Priscila; Wu, Colin O.; Young, Neal S.

    2012-01-01

    Antithymocyte globulin (ATG) + cyclosporine is effective in restoring hematopoiesis in severe aplastic anemia (SAA). We hypothesized that the humanized anti-CD52 mAb alemtuzumab might be active in SAA because of its lymphocytotoxic properties. We investigated alemtuzumab monotherapy from 2003-2010 in treatment-naive, relapsed, and refractory SAA in 3 separate research protocols at the National Institutes of Health. Primary outcome was hematologic response at 6 months. For refractory disease, patients were randomized between rabbit ATG + cyclosporine (n = 27) and alemtuzumab (n = 27); the response rate for alemtuzumab was 37% (95% confidence interval [CI], 18%-57%) and for rabbit ATG 33% (95% CI, 14%-52%; P = .78). The 3-year survival was 83% (95% CI, 68%-99%) for alemtuzumab and 60% (95% CI, 43%-85%) for rabbit ATG (P = .16). For relapsed disease (n = 25), alemtuzumab was administered in a single-arm study; the response rate was 56% (95% CI, 35%-77%) and the 3-year survival was 86% (95% CI, 72%-100%). In treatment-naive patients (n = 16), alemtuzumab was compared with horse and rabbit ATG in a 3-arm randomized study; the response rate was 19% (95% CI 0%-40%), and the alemtuzumab arm was discontinued early. We conclude that alemtuzumab is effective in SAA, but best results are obtained in the relapsed and refractory settings. The present trials were registered at www.clinicaltrials.gov as NCT00195624, NCT00260689, and NCT00065260. PMID:22067384

  12. 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.

  13. Treatment of refractory partial status epilepticus with multiple subpial transection: case report.

    PubMed

    D'Giano, C H; Del C García, M; Pomata, H; Rabinowicz, A L

    2001-07-01

    Status epilepticus (SE) represents a medical emergency that annually affects 60,000--150,000 individuals in the United States. Selective neuronal loss in vulnerable areas has been pathologically demonstrated following convulsive SE primarily affecting the limbic system, thalamus and cerebellum. Morbidity in those cases that follow refractory SE (RSE) is poorly documented. There have been anecdotal reports of surgical treatment for this condition, especially secondary to brain lesions. We report a 6-year-old patient who was in RSE for 60 days, without a brain lesion documented by MRI. The patient underwent multiple subpial transection (MST) of the sensorimotor cortex, which by ictal EEG and ictal SPECT proved to be the epileptogenic zone. We conclude that MST should be considered as an alternative treatment for refractory partial SE.

  14. Resolution of mucus plugging and atelectasis after intratracheal rhDNase therapy in a mechanically ventilated child with refractory status asthmaticus.

    PubMed

    Durward, A; Forte, V; Shemie, S D

    2000-02-01

    To report the dramatic resolution of unilateral mucus plugging and atelectasis in a mechanically ventilated child with refractory status asthmaticus after intratracheal recombinant human DNase (rhDNase) therapy. Case report. Critical care unit. A 7-yr-old boy with status asthmaticus, severe respiratory failure and barotrauma unresponsive to conventional therapy. Fiberoptic bronchoscopy confirmed widespread mucus impaction of the subsegmental bronchi of the left lung without response to bronchoscopic lavage. Two 10-mg doses of intratracheal rhDNase were administered 8 hrs apart. The left-sided atelectasis resolved 3 hrs after the first dose of rhDNase. Improvements in gas exchange and tidal volumes were sustained and particularly noticeable after the second dose. The patient was successfully extubated 26 hrs after receiving the rhDNase treatment without any adverse effects. rhDNase should be considered as a potential therapy for refractory mucus plugging and atelectasis in intubated patients with status asthmaticus.

  15. 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.

  16. Alternative Donor Transplantation with High-Dose Post-Transplantation Cyclophosphamide for Refractory Severe Aplastic Anemia

    PubMed Central

    DeZern, Amy E.; Zahurak, Marianna; Symons, Heather; Cooke, Kenneth; Jones, Richard J.; Brodsky, Robert A.

    2017-01-01

    Severe aplastic anemia (SAA) is a life-threatening hematopoietic stem cell disorder that is treated with bone marrow transplantation (BMT) or immunosuppressive therapy (IST). The management of patients with refractory SAA after IST is a major challenge. Alternative donor BMT is the best chance for cure in refractory SAA, but morbidity and mortality from graft failure and complications of graft-versus-host disease (GVHD) have limited enthusiasm for this approach. Here, we employed post-transplantation high-dose cyclophosphamide in an effort to safely expand the donor pool in 16 consecutive patients with refractory SAA who did not have a matched sibling donor. Between July 2011 and August 2016, 16 patients underwent allogeneic (allo) BMT for refractory SAA from 13 haploidentical donors and 3 unrelated donors. The nonmyeloablative conditioning regimen consisted of antithymocyte globulin, fludarabine, low-dose cyclophosphamide, and total body irradiation. Post-transplantation cyclophosphamide 50 mg/kg/day i.v. on days +3 and +4 was administered for GVHD prophylaxis. Additionally, patients received mycophenolate mofetil on days +5 through 35 and tacrolimus from day +5 through 1 year. The median age of the patients at the time of transplantation was 30 (range, 11 to 69) years. The median time to neutrophil recovery over 1000 × 103/mm3 for 3 consecutive days was 19 (range, 16 to 27) days, to red cell engraftment was 25 (range, 2 to 58) days, and to last platelet transfusion to keep platelets counts over 50 × 103/mm3 was 27.5 (range, 22 to 108) days. Graft failure, primary or secondary, was not seen in any of the patients. All 16 patients are alive, transfusion independent, and without evidence of clonality. The median follow-up is 21 (range, 3 to 64) months. Two patients had grade 1 or 2 skin-only acute GVHD. These same 2 also had mild chronic GVHD of the skin/mouth requiring systemic steroids. One of these GVHD patients was able to come off all IST by 15 months and the

  17. Gonococcus - The culprit of refractory, severe conjunctivitis in an elderly patient.

    PubMed

    Hoffman, Jeremy J S; Ali, Bazga

    2015-12-01

    We present a highly unusual case of microbiologically-confirmed adult gonococcal conjunctivitis in an elderly patient with the absence of genital co-infection and no sexual risk factors. Possible routes of infection are discussed, together with diagnosis and management of gonococcal keratoconjunctivitis. This case serves to highlight the possibility of gonococcal conjunctivitis as a diagnosis in severe, refractory conjunctivitis, even if the patient demographics, lack of pre-existing genital infection or sexual risk factors make gonococcus seem unlikely. Copyright © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  18. Topiramate as an adjunctive treatment in patients with refractory status epilepticus: an observational cohort study.

    PubMed

    Hottinger, Annalena; Sutter, Raoul; Marsch, Stephan; Rüegg, Stephan

    2012-09-01

    Refractory status epilepticus (RSE) is the most severe manifestation of status epilepticus (SE), often requiring intensive care and therapeutic coma. It is associated with prolonged intensive care unit (ICU) and hospital stays, as well as increased morbidity and mortality. Treatment involves both intravenous anaesthetics and antiepileptic drugs (AEDs) that can be administrated intravenously, by nasogastric tube or by percutaneous endoscopic gastrostomy. Experience with some of the newer AEDs for the treatment of RSE is restricted and higher-class evidence regarding tolerability and efficacy is lacking. Topiramate is a potent broad-spectrum AED with several modes of action, including blockade of the ionotropic glutamatergic AMPA receptor, which is likely to be an important mechanism for the treatment of SE. While there is no commercially available intravenous formulation, topiramate can be administered enterally, which may make it suitable for the treatment of RSE. The objective of this study was to evaluate the tolerability, safety profile and efficacy of adjunctive and enterally administered topiramate in patients with RSE. A medical chart review was performed of all consecutive patients treated for RSE between August 2004 and December 2011 at the ICU of the University Hospital Basel (Basel, Switzerland). 113 (43%) of all consecutive 268 patients with SE developed RSE. Of those, 35 (31%) were treated with topiramate. Median age was 60.5 years. Topiramate was used as an add-on treatment after 1-6 (median 4) prior administered AEDs had failed. It was introduced after a median of 2 (range 2-23) days for a duration of 1-24 (median 3) days. The response rate after topiramate administration as the third AED was 86% (6/7 patients), and remained stable at 67% after administration as the fourth, fifth, sixth or seventh AED when the groups of successfully and probably successfully treated patients were pooled. Overall, RSE was terminated in 71% of patients within 72 hours

  19. 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

  20. [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.

  1. New Onset Refractory Status Epilepticus as an Unusual Presentation of a Suspected Organophosphate Poisoning

    PubMed Central

    Waheed, Shahan; Sabeen, Amber; Ullah Khan, Nadeem

    2014-01-01

    New onset refractory status epilepticus (NORSE) is a new entity in medical literature. It has different infectious and noninfectious etiologies showing a devastating impact onto the clinical outcome of patients. Therapy with anaesthetic and antiepileptic agents often fails to improve the condition, unless the primary cause is rectified. Here is presented the case of a young female with a history of depression who after a recent bereavement came to the Emergency Department of Aga Khan University Hospital with complaints of drowsiness that lasted for few hours. Though she had no history of organophosphate poisoning, her physical examination and further investigations were suggestive of the diagnosis. During her hospital stay, she developed refractory status epilepticus. Her seizures did not respond to standard antiepileptic and intravenous anesthetic agents and subsided only after intravenous infusion of atropine for a few days. Organophosphate poisoning is a very common presentation in the developing world and the associated status epilepticus poses a devastating problem for emergency physicians. In patients with suspected organophosphate poisoning with favoring clinical exam findings, the continuation of atropine intravenous infusion can be a safe option to abate seizures. PMID:25580311

  2. Super-refractory status epilepticus and febrile infection-related epilepsy syndrome treated with anakinra

    PubMed Central

    Kenney-Jung, Daniel L.; Kahoud, Robert J.; Vezzani, Annamaria; LaFrance-Corey, Reghann G.; Ho, Mai-Lan; Muskardin, Theresa Wampler; Gleich, Stephen J.; Wirrell, Elaine C.; Howe, Charles L.; Payne, Eric T.

    2017-01-01

    Febrile infection-related epilepsy syndrome (FIRES) is a devastating epileptic encephalopathy with limited treatment options and an unclear etiology. Anakinra is a recombinant version of the human interleukin-1 receptor antagonist used to treat autoinflammatory disorders. This is the first report of anakinra for treatment of a child with super-refractory status epilepticus secondary to FIRES. Anakinra was well-tolerated and effective. Cerebral spinal fluid analysis revealed elevated levels of proinflammatory cytokines before treatment that normalized on anakinra, suggesting a potential pathogenic role for neuroinflammation in FIRES. Further studies are required to assess anakinra efficacy and dosing, and to further delineate disease etiology. PMID:27770579

  3. Detoxification combining fasting with fluid therapy for refractory cases of severe atopic dermatitis.

    PubMed

    Kim, Kyu Seok; Nam, Hae Jeong

    2013-01-01

    To introduce and determine the clinical benefits of a detoxification program that combines fasting with fluid therapy for refractory cases of severe atopic dermatitis (AD), we performed a retrospective chart review of inpatients with AD from March 2010 to February 2012 at the Department of Ophthalmology, Otorhinolaryngology and Dermatology of Korean Medicine in the Kyung Hee Medical Center. Patients were treated with the detoxification program, which combined fasting with fluid therapy, and herbal medicine, herbal wet wrap dressings, or acupuncture treatment when clinically necessary. The primary outcome was the SCORAD total index. The secondary outcome was the pruritus visual analogue scale (VAS) score in SCORAD as evaluated by a trained dermatology specialist. Among the 130 inpatients that have done detoxification, 7 patients met the inclusion criteria. The mean total SCORAD scores significantly decreased from 64.67 ± 11.72 to 26.26 ± 11.01 (P = 0.018) after the detoxification program. There was also a significant decrease in VAS score for pruritus from 8.00 ± 1.16 to 2.57 ± 0.98 (P = 0.016) between admission and discharge. We suggest that fasting with fluid therapy as a complementary and alternative treatment method may provide some benefits for patients with refractory cases of severe atopic dermatitis.

  4. 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

  5. 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.

  6. New-Onset Refractory Status Epilepticus with Claustrum Damage: Definition of the Clinical and Neuroimaging Features

    PubMed Central

    Meletti, Stefano; Giovannini, Giada; d’Orsi, Giuseppe; Toran, Lisa; Monti, Giulia; Guha, Rahul; Kiryttopoulos, Andreas; Pascarella, Maria Grazia; Martino, Tommaso; Alexopoulos, Haris; Spilioti, Martha; Slonkova, Jana

    2017-01-01

    New-onset refractory status epilepticus (NORSE) is a rare but challenging condition occurring in a previously healthy patient, often with no identifiable cause. We describe the electro-clinical features and outcomes in a group of patients with NORSE who all demonstrated a typical magnetic resonance imaging (MRI) sign characterized by bilateral lesions of the claustrum. The group includes 31 patients (12 personal and 19 previously published cases; 17 females; mean age of 25 years). Fever preceded status epilepticus (SE) in 28 patients, by a mean of 6 days. SE was refractory/super-refractory in 74% of the patients, requiring third-line agents and a median of 15 days staying in an intensive care unit. Focal motor and tonic–clonic seizures were observed in 90%, complex partial seizures in 14%, and myoclonic seizures in 14% of the cases. All patients showed T2/FLAIR hyperintense foci in bilateral claustrum, appearing on average 10 days after SE onset. Other limbic (hippocampus, insular) alterations were present in 53% of patients. Within the personal cases, extensive search for known autoantibodies was inconclusive, though 7 of 11 patients had cerebrospinal fluid lymphocytic pleocytosis and 3 cases had oligoclonal bands. Two subjects died during the acute phase, one in the chronic phase (probable sudden unexplained death in epilepsy), and one developed a persistent vegetative state. Among survivors, 80% developed drug-resistant epilepsy. Febrile illness-related SE associated with bilateral claustrum hyperintensity on MRI represents a condition with defined clinical features and a presumed but unidentified autoimmune etiology. A better characterization of de novo SE is mandatory for the search of specific etiologies. PMID:28396650

  7. Mepolizumab for severe refractory eosinophilic asthma: evidence to date and clinical potential

    PubMed Central

    Menzella, Francesco; Lusuardi, Mirco; Galeone, Carla; Taddei, Sofia; Facciolongo, Nicola; Zucchi, Luigi

    2016-01-01

    Severe asthma is characterized by major impairment of quality of life, poor symptom control and frequent exacerbations. Inflammatory, clinical and causative factors identify different phenotypes and endotypes of asthma. In the last few years, new treatment options have allowed for targeted treatments according to the different phenotypes of the disease. To accurately select a specific treatment for each asthmatic variant, the identification of appropriate biomarkers is required. Eosinophilic asthma is a distinct phenotype characterized by thickening of the basement membrane and corticosteroid responsiveness. This review reports the latest evidence on an anti-IL-5 monoclonal antibody, mepolizumab, a new and promising biological agent recently approved by the FDA specifically for the treatment of severe eosinophilic refractory asthma. PMID:27803792

  8. Causes and outcomes of new onset status epilepticus and predictors of refractoriness to therapy.

    PubMed

    Jayalakshmi, Sita; Vooturi, Sudhindra; Sahu, Sambit; Yada, Praveen Kumar; Mohandas, Surath

    2016-04-01

    We aimed to evaluate the determinants of outcome in new onset refractory status epilepticus (SE). A retrospective analysis of patients with new onset SE admitted between May 2005 and October 2013 was performed. Regression analysis was used to determine factors that affect progression of new onset SE to refractory status epilepticus (RSE) and mortality. Among 114 patients with new onset SE, 52 patients progressed to RSE. Sixty seven (58.7%) were men. New onset RSE patients were younger than new onset SE patients (mean 35.9 ± standard deviation18.2 versus 28.7 ± 20.2 years; p=0.050). Cryptogenic aetiology was the most significant determinant of progression of new onset SE to RSE (Exp [β]=5.68; p=0.001). The overall mortality in the entire group was 23.7%, significantly higher in new onset RSE group (40.4% versus 9.7%; p<0.0001). New onset RSE patients with symptomatic and cryptogenic etiology did not differ for clinical characteristics and outcome. Acidosis was the strongest predictor of mortality in the entire cohort (Exp [β]=8.72; p=0.005). Nearly half of the patients with new onset SE progressed to RSE. While cryptogenic aetiology determined progression of new onset SE to RSE, acidosis was associated with mortality. The outcome was similar between symptomatic and cryptogenic new onset RSE. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Continuous Infusion Antiepileptic Medications for Refractory Status Epilepticus: A Review for Nurses.

    PubMed

    Wiss, Adam L; Samarin, Michael; Marler, Jacob; Jones, G Morgan

    Status epilepticus requires treatment with emergent initial therapy with a benzodiazepine and urgent control therapy with an additional antiepileptic drug (AED) to terminate clinical and/or electrographic seizure activity. However, nearly one-third of patients will prove refractory to the aforementioned therapies and are prone to a higher degree of neuronal injury, resistance to pharmacotherapy, and death. Current guidelines for refractory status epilepticus (RSE) recommend initiating a continuous intravenous (CIV) anesthetic over bolus dosing with a different AED. Continuous intravenous agents most commonly used for this indication include midazolam, propofol, and pentobarbital, but ketamine is an alternative option. Comparative studies illustrating the optimal agent are lacking, and selection is often based on adverse effect profiles and patient-specific factors. In addition, dosing and titration are largely based on small studies and expert opinion with continuous electroencephalogram monitoring used to guide intensity and duration of treatment. Nonetheless, the doses required to halt seizure activity are likely to produce profound adverse effects that clinicians should anticipate and combat. The purpose of this review was to summarize the available RSE literature focusing on CIV midazolam, pentobarbital, propofol, and ketamine, and to serve as a primer for nurses providing care to these patients.

  10. Chaos theory and the treatment of refractory status epilepticus: Who benefits from prolonged anesthesia, and is there a better way?

    PubMed

    Hutchinson, Michael; Swanson, Phillip D

    2007-01-01

    Refractory status epilepticus (SE) is a condition of continuous seizure activity in which there is a regular, rapid, succession of spike discharges in the brain. It is incompatible with normal consciousness and is associated with an extremely high morbidity and mortality. Prior to 1990, prevailing opinion held that a brief period of anesthesia (up to two weeks) was to be recommended, but that if SE persisted this was a sign of irreversible brain damage. Therefore support of the patient in SE was not recommended beyond two weeks. On the basis of the theoretical constructs of chaos theory we hypothesized that, for selected cases, anesthesia should be continued indefinitely until the SE resolved. This became the standard of care at the University of Washington and at other institutions. After several years, the accumulating evidence lends support for this hypothesis and we are now able to propose which patients will benefit from such therapy. It is hypothesized that only those patients for whom there is no underlying brain disease, beyond epilepsy, are likely to benefit. Secondly, chaos theory suggests that a strong perturbation will cause a rapid transition from the stable attractor of SE to the stable attractor representing normal consciousness. In certain ways, SE is analogous to ventricular tachycardia, where the cardiac muscle has an abnormally fast rhythm incompatible with proper cardiac function. Therefore the second hypothesis is that a brain perturbation, analogous to defibrillation, may be even more useful than anesthesia in refractory SE.

  11. Tacrolimus Eye Drops as Adjunct Therapy in Severe Corneal Endothelial Rejection Refractory to Corticosteroids.

    PubMed

    Ghaffari, Reza; Ghassemi, Hamed; Zarei-Ghanavati, Mehran; Latifi, Golshan; Dehghani, Shima; Haq, Zeeshan; Djalilian, Ali R

    2017-10-01

    To evaluate the safety and efficacy of tacrolimus eye drops as adjunctive therapy in the treatment of severe corneal endothelial rejection after penetrating keratoplasty refractory to corticosteroids. In this prospective interventional case series, 11 eyes of 11 patients assessed for severe corneal endothelial rejection, with an inadequate response to topical, local, and systemic corticosteroids, were treated with either 0.01% or 0.05% tacrolimus eye drops 4 times daily. Improvement in signs of rejection, visual function, and development of complications were monitored. The duration of steroid treatment before intervention was 8.1 ± 1.4 days (range = 7-11). Patients were subsequently administered topical tacrolimus 0.01% or 0.05% qid. The time to clinical improvement was 10.3 ± 3.4 days (range = 3-17). The time to rejection reversal was 27.8 ± 16.3 days (range = 7-52). After 3 months, 10 patients (90.8%) demonstrated clinical improvement, and complete restoration of graft clarity was achieved in 5 patients (45.4%). In responsive cases, steroid therapy was successfully tapered off after 60.2 ± 19.7 days (range = 36-93). The best spectacle-corrected visual acuity improved from 1.7 ± 0.9 to 0.8 ± 0.5 logMAR (P = 0.0016). Reported side effects included stinging on drop instillation and punctate epithelial keratopathy. Tacrolimus eye drops may be able to play an adjunctive therapeutic role in patients with severe corneal endothelial rejection refractory to conventional steroid treatment. Controlled studies are needed to further investigate the role of tacrolimus in this setting.

  12. Mild hypothermia for refractory focal status epilepticus in an infant with hemimegalencephaly.

    PubMed

    Elting, Jan Willem; Naalt, Joukje van der; Fock, Johanna Maria

    2010-09-01

    Hypothermia can reduce seizure frequency in animal models of status epilepticus, and its effectiveness in human status epilepticus has been reported occasionally. We report an infant with hemimegalencephaly who presented with generalized status epilepticus. After high dose intravenous drug therapy, this converted to focal status epilepticus in the right occipital region. A sudden cessation of all seizure activity was found to coincide with accidental hypothermia. After application of mild continuous hypothermia, a marked reduction of seizure frequency occurred, which allowed reduction of intravenous drug doses and discharge from the IC unit. Ultimately, hemispherectomy was needed to achieve long term seizure control. The therapeutic effect of hypothermia should be further investigated in patients with refractory status epilepticus. When used in combination with anti-epileptic drugs, seizure control may be achieved at lower doses. Hypothermia may obviate the need for potentially dangerous barbiturate therapy. This case demonstrates that even a mild degree of hypothermia (+/-36 degrees C) can be remarkably effective. Copyright (c) 2009. Published by Elsevier Ltd.

  13. Enteral topiramate in a pediatric patient with refractory status epilepticus: a case report and review of the literature.

    PubMed

    Shelton, Chasity M; Alford, Elizabeth L; Storgion, Stephanie; Wheless, James; Phelps, Stephanie J

    2014-01-01

    We describe the use of topiramate in a healthy 12-year-old (88-kg) male who developed refractory generalized convulsive status epilepticus. Seizures persisted despite aggressive use of benzodiazepines (intravenous lorazepam; oral clorazepate), barbiturates (i.e., phenobarbital, pentobarbital), and hydantoins. The child's seizures were controlled with nasogastrically administered topiramate in doses up to 500 mg twice daily (11.4 mg/kg/day). The patient did not display any clinical or laboratory signs of metabolic acidosis while receiving topiramate. Topiramate should be considered as a treatment option in refractory status epilepticus.

  14. Enteral Topiramate in a Pediatric Patient with Refractory Status Epilepticus: A Case Report and Review of the Literature

    PubMed Central

    Shelton, Chasity M.; Alford, Elizabeth L.; Storgion, Stephanie; Wheless, James

    2014-01-01

    We describe the use of topiramate in a healthy 12-year-old (88-kg) male who developed refractory generalized convulsive status epilepticus. Seizures persisted despite aggressive use of benzodiazepines (intravenous lorazepam; oral clorazepate), barbiturates (i.e., phenobarbital, pentobarbital), and hydantoins. The child's seizures were controlled with nasogastrically administered topiramate in doses up to 500 mg twice daily (11.4 mg/kg/day). The patient did not display any clinical or laboratory signs of metabolic acidosis while receiving topiramate. Topiramate should be considered as a treatment option in refractory status epilepticus. PMID:25762878

  15. Deep brain stimulation for the treatment of severe, medically refractory obsessive-compulsive disorder.

    PubMed

    Sedrak, Mark; Wong, William; Wilson, Paul; Bruce, Diana; Bernstein, Ivan; Khandhar, Suketu; Pappas, Conrad; Heit, Gary; Sabelman, Eric

    2013-01-01

    Deep brain stimulation is a rapidly expanding therapy initially designed for the treatment of movement disorders and pain syndromes. The therapy includes implantation of electrodes in specific targets of the brain, delivering programmable small and safe electric impulses, like a pacemaker, that modulates both local and broad neurologic networks. The effects are thought to primarily involve a focus in the brain, probably inhibitory, which then restores a network of neural circuitry. Psychiatric diseases can be refractory and severe, leading to high medical costs, significant morbidity, and even death. Whereas surgery for psychiatric disease used to include destructive procedures, deep brain stimulation allows safe, reversible, and adjustable treatment that can be tailored for each patient. Deep brain stimulation offers new hope for these unfortunate patients, and the preliminary results are promising.

  16. Experience with onabotulinumtoxinA (BOTOX) in chronic refractory migraine: focus on severe attacks.

    PubMed

    Oterino, A; Ramón, C; Pascual, J

    2011-04-01

    The objective of this study is to analyse our experience in the treatment of refractory chronic migraine (CM) with onabotulinumtoxinA (BTA) and specifically in its effects over disabling attacks. Patients with CM and inadequate response or intolerance to oral preventatives were treated with pericranial injections of 100 U of TBA every 3 months. The dose was increased up to 200 U in case of no response. The patients kept a headache diary. In addition, we specifically asked on the effect of BTA on the frequency of disabling attacks, consumption of triptans and visits to Emergency for the treatment of severe attacks. This series comprises a total of 35 patients (3 males), aged 24-68 years. All except three met IHS criteria for analgesic overuse. The number of sessions with BTA ranged from 2 to 15 (median 4) and nine (26%) responded (reduction of >50% in headache days). However, the frequency of severe attacks was reduced to an average of 46%. Oral triptan consumption (29 patients) was reduced by 50% (from an average of 22 to 11 tablets/month). Those six patients who used subcutaneous sumatriptan reduced its consumption to a mean of 69% (from 4.5 to 1.5 injections per month). Emergency visits went from an average of 3 to 0.4 per trimester (-83%). Six patients complained of mild adverse events, transient local cervical pain being the most common. Although our data must be taken with caution as this is an open trial, in clinical practice treatment of refractory CM with BTA reduces the frequency of disabling attacks, the consumption of triptans and the need of visits to Emergency, which makes this treatment a profitable option both clinically and pharmacoeconomically. © The Author(s) 2011. This article is published with open access at Springerlink.com

  17. Treatment of severe refractory pruritus with fractionated plasma separation and adsorption (Prometheus).

    PubMed

    Rifai, Kinan; Hafer, Carsten; Rosenau, Jens; Athmann, Christoph; Haller, Hermann; Peter Manns, Michael; Fliser, Danilo

    2006-10-01

    Severe pruritus is a serious complication of cholestatic liver disease. Prometheus is a recently introduced extracorporeal liver support system with direct toxin adsorption of the patient's albumin fraction (FPSA; fractionated plasma separation and adsorption). Here we report on the effect of Prometheus therapy in patients with intractable cholestatic pruritus. Seven patients with different liver diseases and severe pruritus refractory to all medical treatment efforts for more than 4 weeks were treated with Prometheus (3-5 times, 18+/-3 h total). Pruritus intensity was assessed using the visual analogue scale (VAS; from 0 = no pruritus to 10 = unbearable pruritus), and VAS, serum bile acids and total bilirubin were evaluated directly before and after Prometheus treatment, as well as 4 weeks later. After Prometheus therapy, VAS values had dropped significantly from 9+/-1 to 3+/-3 (p<0.001). Likewise, serum bile acids decreased (from 248+/-192 to 101+/-85 micromol/l; p<0.03). All patients, with the exception of one with no initial bile acid elevation, reported a pronounced improvement in pruritus with Prometheus therapy, although in two anicteric patients the amelioration lasted only a few days. In the other four patients a distinct benefit was still observed 4 weeks after the treatment. Prometheus therapy significantly improved refractory pruritus in all patients with elevated bile acid levels, but in some patients the clinical benefit was of short duration. The clinical findings suggest that we have to better characterize those patients who might derive a long-lasting benefit from this invasive and expensive treatment.

  18. Incidence and mortality of super-refractory status epilepticus in adults.

    PubMed

    Kantanen, Anne-Mari; Reinikainen, Matti; Parviainen, Ilkka; Ruokonen, Esko; Ala-Peijari, Marika; Bäcklund, Tom; Koskenkari, Juha; Laitio, Ruut; Kälviäinen, Reetta

    2015-08-01

    Super-refractory status epilepticus (SRSE) is defined as status epilepticus (SE) that continues or recurs 24h or more after the onset of anesthetic therapy. We defined the incidence and outcome of SRSE in adults in Finland. We analyzed retrospectively the Finnish Intensive Care Consortium database in order to identify adult patients with SRSE treated in ICUs in Finland during a three-year period (2010-2012). The database consists of admissions to all 20 Finnish hospitals treating refractory SE (RSE) with general anesthesia in the intensive care unit (ICU). We included consecutive adult (16 years or older) patients with RSE and identified those who had SRSE. Patients with postanoxic etiologies were excluded. All five university hospitals and 10/15 of the central hospitals participated. The adult referral population of the study hospitals is 3.9 million, representing 91% of the total adult population of Finland. We identified 395 patients with ICU-treated RSE, 87 (22%) of whom were classified as having SRSE. This corresponds to an annual incidence of SRSE of 0.7/100,000 (95% confidence interval [CI]: 0.6-0.9). The one-year mortality rates were 36% (95% CI: 26-46%) for patients with SRSE and 22% (95% CI: 17-27%) for patients with RSE. Mortality was highest (63%) in patients with SRSE aged over 75 years. Approximately 20% of patients with RSE treated in Finnish ICUs progressed to having SRSE. The incidence of SRSE, 0.7/100,000, is about 5-10% of the incidence of SE. The mortality of patients with SRSE, 36%, was comparable to earlier studies and twofold higher than the mortality of patients with RSE. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

  19. 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

    2017-09-09

    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.

  20. 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

  1. Current Trends in Treatment of Status Epilepticus and Refractory Status Epilepticus.

    PubMed

    Betjemann, John P

    2015-12-01

    Status epilepticus is a heterogeneous disorder with varied definitions and presentations. Taken together, all forms of status epilepticus carry significant morbidity and mortality, much of which is dictated by the underlying etiology. Generalized convulsive status epilepticus, which represents a common form, is a true neurologic emergency that requires emergent management. Treatment focuses on stabilizing the patient and aggressive medical management to achieve the timely termination of seizures. For other forms of status epilepticus including nonconvulsive and focal status epilepticus, the goal remains early seizure termination, but the use of intravenous medications should be weighed against the risks associated with these therapies. The diagnostic evaluation of status epilepticus is guided by the patient's history and should be broad, including a screen for toxins, electrolytes, structural abnormalities, and central nervous system infectious and autoimmune/inflammatory etiologies. Considerable research is still needed to improve our understanding of the mechanisms, consequences, and therapy of status epilepticus. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  2. RISK OF SEVERE AND REFRACTORY POSTOPERATIVE NAUSEA AND VOMITING IN PATIENTS UNDERGOING DIEP FLAP BREAST RECONSTRUCTION

    PubMed Central

    MANAHAN, MICHELE A.; BASDAG, BASAK; KALMAR, CHRISTOPHER L.; SHRIDHARANI, SACHIN M.; MAGARAKIS, MICHAEL; JACOBS, LISA K.; THOMSEN, ROBERT W.; ROSSON, GEDGE D.

    2014-01-01

    Background Postoperative nausea and vomiting (PONV) are commonly feared after general anesthesia and can impact results. The primary aim of our study was to examine incidence and severity of PONV by investigating complete response, or absence of PONV, to prophylaxis used in patients undergoing DIEP flaps. Our secondary aims were definition of the magnitude of risk, state of the art of interventions, clinical sequelae of PONV, and interaction between these variables, specifically for DIEP patients. Methods A retrospective chart review occurred for 29 patients undergoing DIEP flap breast reconstruction from September 2007 to February 2008. We assessed known patient and procedure-specific risks for PONV after DIEPs, prophylactic antiemetic regimens, incidence, and severity of PONV, postoperative antiemetic rescues, and effects of risks and treatments on symptoms. Results Three or more established risks existed in all patients, with up to seven risks per patient. Although 90% of patients received diverse prophylaxis, 76% of patients experienced PONV, and 66% experienced its severe form, emesis. Early PONV (73%) was frequent; symptoms were long lasting (average 20 hours for nausea and emesis); and multiple rescue medications were frequently required (55% for nausea, 58% for emesis). Length of surgery and nonsmoking statistically significantly impacted PONV. Conclusion We identify previously undocumented high risks for PONV in DIEP patients. High frequency, severity, and refractoriness of PONV occur despite standard prophylaxis. Plastic surgeons and anesthesiologists should further investigate methods to optimize PONV prophylaxis and treatment in DIEP flap patients. PMID:24038427

  3. Drug-induced EEG pattern predicts effectiveness of ketamine in treating refractory status epilepticus.

    PubMed

    Basha, Maysaa M; Alqallaf, Abdulradha; Shah, Aashit K

    2015-04-01

    Refractory status epilepticus (RSE) can lack overt clinical manifestation and is usually treated with continuous infusion of intravenous anesthetic drugs (IVADs), where the use of continuous electroencephalography (cEEG) is imperative. Ketamine has recently been shown to be effective in the treatment of RSE. We retrospectively review a cohort of 11 patients receiving ketamine as part of their treatment regimen for RSE. We report on the presence of a characteristic EEG rhythm consisting of a generalized archiform theta to beta rhythms (7-20 Hz) appearing after ketamine administration. This pattern was seen in five patients, four of whom achieved successful resolution of RSE. Ketamine-induced EEG pattern may serve as a biomarker predictive of successful treatment outcome in RSE. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  4. Complications during the management of pediatric refractory status epilepticus with benzodiazepine and pentobarbital infusions.

    PubMed

    Patten, William; Naqvi, Sayed Z; Raszynski, Andre; Totapally, Balagangadhar R

    2015-05-01

    The objective of this retrospective study was to evaluate complications in the management of refractory status epilepticus (RSE) treated with benzodiazepine and pentobarbital infusions. Of 28 children with RSE, eleven (39%) were treated with a pentobarbital infusion after failure to control RSE with a benzodiazepine infusion; while17 children (61%) required only a benzodiazepine infusion. The mean maximum pentobarbital infusion dosage was 5.2 ± 1.8 mg/kg/h. Twenty-five patients received a continuous midazolam infusion with an average dosage of 0.41 ± 0.43 mg/kg/h. The median length of stay was longer for the pentobarbital group. Children requiring pentobarbital therapy were more likely to develop hypotension, require inotropic support, need intubation, mechanical ventilation, peripheral nutrition, and blood products; furthermore, they were more likely to develop hypertension and movement disorder after or during weaning. In conclusion, children with RSE who required pentobarbital therapy had a longer hospital stay with more complications.

  5. 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

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

    PubMed

    Barzegar, Mohammad; Mahdavi, Mohammad; Galegolab Behbehani, Afshin; Tabrizi, Aidin

    2015-01-01

    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. 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. 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). 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.

  7. Oxycodone/Naloxone PR: A Review in Severe Refractory Restless Legs Syndrome.

    PubMed

    Frampton, James E

    2015-06-01

    An oral, fixed-dose combination of prolonged-release (PR) oxycodone with PR naloxone (Targin(®), Targiniq(®), Targinact(®); hereafter referred to as oxycodone/naloxone PR) is approved in Europe for the second-line symptomatic treatment of patients with severe to very severe idiopathic restless legs syndrome (RLS), after failure of dopaminergic therapy. Coadministration of naloxone represents a targeted approach to counteracting opioid-induced bowel dysfunction without compromising therapeutic efficacy; because of its very low oral bioavailability, naloxone blocks the action of oxycodone at opioid receptors locally in the gut. The efficacy of oxycodone/naloxone PR in patients with severe RLS inadequately controlled by previous (mainly dopaminergic) treatment has been demonstrated in RELOXYN, a 12-week, randomized, double-blind study with a 40-week open-label extension. In this pivotal study, oxycodone/naloxone PR significantly improved RLS symptoms compared with placebo from week 2 onwards; a beneficial effect of oxycodone/naloxone PR was maintained through 1 year of treatment. Furthermore, improvements in RLS symptoms in oxycodone/naloxone PR recipients were accompanied by similarly sustained improvements in disease-specific quality of life and subjective sleep variables. Oxycodone/naloxone PR was generally well tolerated, with a treatment-related adverse event profile (e.g. gastrointestinal disorders, CNS disorders, fatigue and pruritus) that was consistent with that expected for opioid therapy. Notably, there were no confirmed cases of augmentation among oxycodone/naloxone PR recipients throughout the course of the study. Results from the well-designed RELOXYN trial have thus demonstrated the value of oxycodone/naloxone PR as a second-line therapy for severe refractory RLS; further investigation of this combination product as a first-line treatment for severe RLS is now warranted.

  8. Effects of nebulized sodium cromoglycate on adult patients with severe refractory asthma.

    PubMed

    Sano, Yasuyuki; Adachi, Mitsuru; Kiuchi, Takahiro; Miyamoto, Terumasa

    2006-03-01

    Many patients with severe refractory asthma, which is insufficiently controlled by additional high-dose of inhaled corticosteroids, require oral corticosteroids and/or immunosuppressant. Clinicians should seek for suitable medications, for its' chronic use may induce high risk of side effects. The purpose of this study was to evaluate the efficacy and safety of nebulized sodium cromoglycate (3-4 times/day) in adult severe asthmatic patients with poorly controlled asthmatic symptoms, despite treatments with high-dose inhaled corticosteroids. Adult patients with severe asthma (n=251) were enrolled in a randomized clinical trial at 30 medical centers in Japan. Isotonic saline was used as placebo. The study was conducted for 10 weeks; with initial 2 weeks of observation followed by 8 weeks of treatments. Efficacy was primarily evaluated based on improvements in morning peak expiratory flow after treatment. All patients who applied inhalation of nebulized sodium cromoglycate (SCG group) or saline (Controls) were treated with high-dose of inhaled corticosteroids (median of beclomethasone dipropionate equivalent dose: 1600 microg/days) and second-line control therapy including oral corticosteroids. There was no significant difference in morning peak expiratory flow between SCG group and controls. However, when patients were stratified into atopic and non-atopic groups, morning peak expiratory flow had significantly improved in the atopic SCG group compared to atopic Controls. Additional inhalation of nebulized sodium cromoglycate with inhaled corticosteroids is effective even in patients with severe atopic asthma. This finding shows that nebulized sodium cromoglycate is expected to be new second-line therapeutic option in severe asthma.

  9. 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…

  10. 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…

  11. Seizures – just the tip of the iceberg: Critical care management of super-refractory status epilepticus

    PubMed Central

    Lionel, Karen Ruby; Hrishi, Ajay Prasad

    2016-01-01

    Super-refractory status epilepticus (SRSE) is defined as status epilepticus (SE) that continues or recurs 24 h or more after the onset of anesthetic therapy, including those cases where SE recurs on the reduction or withdrawal of anesthesia. Although SRSE is a rare clinical problem, it is associated with high mortality and morbidity rates. This article reviews the treatment approaches and the systemic complications commonly encountered in patients with SRSE. As evident in our search of literature, therapy for SRSE and its complications have been based on clinical reports and expert opinions since there is a lack of controlled and randomized trials. Even though this complex condition starts as a neurological disorder, because of the associated systemic complications, it can be considered as a multisystem disorder requiring scrupulous attention and deliberate efforts to prevent, detect, and treat these systemic effects. We have critically reviewed the intensive care management for SRSE per se as well as its associated systemic complications. We believe that a good recovery can occur even after prolonged and severe SRSE as long as the systemic complications are detected early and managed appropriately. PMID:27829714

  12. [Refractory status epilepticus in children: characterisation of epilepsies, continuous electroencephalographic monitoring and response to treatment].

    PubMed

    Cardoso, Ingrid; Acevedo, Keryma; Hernández, Marta; Santin, Julia; Moya, Pedro; Godoy, Jaime; Castillo, Andrés; Soto, Pilar; Mesa, Tomás

    2013-04-16

    Patients with refractory status epilepticus (RSE) have high morbidity and mortality rates, are hospitalised for longer periods of time, suffer greater neurological damage and progress to symptomatic epilepsy. Continuous electroencephalogram (cEEG) monitoring is a valuable aid in the early detection of RSE, especially in the case of non-convulsive status epilepticus (NCSE). In this study we describe the clinical characteristics, treatment and use of cEEG in paediatric patients with RSE. A retrospective study was conducted at the Hospital Clinico de la Pontificia Universidad Catolica de Chile between November 2005 and March 2011 in patients aged between 1 month and 15 years diagnosed with RSE and cEEG. Demographic characteristics, baseline and final conditions, and therapy were recorded. A total of 15 patients, 12 of whom were males, with a mean age of 4 years (1.5 months-13 years) were identified. Eight patients had a history of epilepsy. The most frequent aetiologies were progressive symptomatic and acute symptomatic. Convulsive epileptic status (CSE) was present in 11 patients and NCSE in the other four. During the cEEG, six of the 11 patients with CSE later progressed to NCSE. The mean amount of time with RSE was 10.2 days. Of the 15 patients, 13 responded to anticonvulsive drugs and the main secondary complications were respiratory depression and hypotension. Patients with CSE tended to evolve in a more torpid manner than patients with NCSE. On discharge from hospital, 13 patients (86.6%) presented new neurological deficit or difficult-to-manage epilepsy, one still had RSE and one died (6%). The aggregate neurological morbidity and mortality rates of RSE were high. The use of cEEG monitoring should be considered for use in the management of such cases of status epilepticus.

  13. 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.

  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. Early predictors of refractory status epilepticus: an international two-center study.

    PubMed

    Sutter, R; Kaplan, P W; Marsch, S; Hammel, E M; Rüegg, S; Ziai, W C

    2015-01-01

    Status epilepticus (SE) refractory to first- and second-line antiepileptic drugs carries high mortality. Little is known on early prediction of refractory SE (RSE)—an essential tool for planning appropriate therapy. Our aim was to identify and validate independent early RSE predictors in adults. Clinical and laboratory data on consecutive intensive care unit patients with SE from two academic care centers (a derivation data set from a Swiss center and a validation data set from a US center) were assessed. Multivariable analysis was performed with the derivation set to identify RSE predictors at SE onset. Their external validity was evaluated with an independent validation set. Measures of calibration and discrimination were assessed. In all, 302 patients were analyzed (138 with and 164 without RSE), 171 in the derivation data set and 131 in the validation data set. Acute SE etiology, coma/stupor and serum albumin <35 g/l at SE onset were independent predictors for RSE in the derivation data set [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.01-4.07; OR 4.83, 95% CI 2.42-9.68; OR 2.45, 95% CI 1.16-5.16]. The prediction model showed good measures of calibration (Hosmer-Lemesow goodness-of-fit test P = 0.99) and discrimination (area under the receiver operating characteristic curve 0.8) on the derivation data set—results that were similar in the validation data set (Hosmer-Lemeshow P = 0.24; area under the receiver operating characteristic curve 0.73). This study confirms the independent prognostic value of readily available parameters for early RSE prediction. Prospective studies are needed to identify additional robust predictors, which could be added to the proposed model for further optimization towards a reliable prediction scoring system. © 2014 EAN.

  16. Efficacy and safety of ketamine in refractory status epilepticus in children.

    PubMed

    Rosati, Anna; L'Erario, Manuela; Ilvento, Lucrezia; Cecchi, Costanza; Pisano, Tiziana; Mirabile, Lorenzo; Guerrini, Renzo

    2012-12-11

    To evaluate the efficacy and safety of ketamine (KE) in the management of refractory convulsive status epilepticus (RSE) in children. In November 2009, we started using KE for treating all children consecutively referred for RSE. Clinical and treatment data were analyzed. Between November 2009 and June 2011, 9 children with RSE received IV KE. In 8 patients, SE had persisted for more than 24 hours (super-refractory RSE), with a median of 6 days (mean 8.5 ± 7.5; range 2-26 days). Prior to KE administration, conventional anesthetics were used, including midazolam, thiopental, and propofol in 9, 5, and 4 patients each. Median dose of KE in continuous IV infusion was 40 gamma(μg)/kg/min (mean 36.5 ± 18.6 gamma[μg]/kg/min; range 10-60 gamma[μg]/kg/min). Midazolam was administered add-on to prevent emergence reactions. The use of KE was associated with resolution of RSE in 6 children. None of the patients experienced serious adverse events. Among the 3 individuals who did not respond to KE, 2 were cured by surgical removal of epileptogenic focal cortical dysplasia. In this small, open-label, unblinded series with no concurrent control group, KE appears effective and safe in treating RSE in children. Larger, randomized studies are needed to confirm data emerging from this preliminary observation. This study provides Class IV evidence that IV KE can be effective in treating children with RSE (no statistical analysis was done).

  17. 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

  18. Clobazam: An effective add-on therapy in refractory status epilepticus.

    PubMed

    Sivakumar, Sanjeev; Ibrahim, Mohammad; Parker, Dennis; Norris, Gregory; Shah, Aashit; Mohamed, Wazim

    2015-06-01

    Refractory status epilepticus (RSE) is a medical emergency, with significant morbidity and mortality. The use and effectiveness of clobazam, a unique 1,5-benzodiazepine, in the management of RSE has not been reported before. Over the last 24 months, we identified 17 patients with RSE who were treated with clobazam in our hospital. Eleven of the 17 patients had prior epilepsy. Fifteen patients had focal status epilepticus. Use of clobazam was prompted by a favorable pharmacokinetic profile devoid of drug interactions. Clobazam was introduced after a median duration of 4 days and after a median of three failed antiepileptic drugs. A successful response, defined as termination of RSE within 24 h of administration, without addition or modification of concurrent AED and with successful wean of anesthetic infusions, was seen in 13 patients. Indeterminate response was seen in three patients, whereas clobazam was unsuccessful in one patient. Clobazam averted the need for anesthetic infusions in five patients. Clobazam was well tolerated, and appears to be an effective and promising option as add-on therapy in RSE. Its efficacy, particularly early in the course of SE, should be further investigated in prospective, randomized trials. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  19. The role of ketogenic diet in the treatment of refractory status epilepticus.

    PubMed

    Nam, Sook Hyun; Lee, Bo Lyun; Lee, Cha Gon; Yu, Hee Joon; Joo, Eun Yeon; Lee, Jeehun; Lee, Munhyang

    2011-11-01

    Ketogenic diet (KD) is known to be effective in intractable epilepsy. However, the role of KD in refractory status epilepticus (RSE) has not been well described. The aim of this study is to explore the role of KD in patients with RSE. We retrospectively reviewed the medical records of four children and one adult with RSE between October 2006 and August 2010. All presented with status epilepticus (SE) that was presumed to be associated with viral encephalitis. After we failed to control the seizures with standard measures for SE, we tried KD. The overall seizure frequency decreased to <50% of baseline in median eight (1-19) days. At one month of KD, two patients were seizure-free, one patient showed >90% seizure reduction, and the others had >75% decrease without generalized seizures. With improvement in the RSE, we were able to taper the antiepileptic drugs (AEDs) and wean patients from prolonged mechanical ventilation. The adverse events of KD in RSE included aspiration pneumonia, gastroesophageal reflux, constipation, and hypertriglyceridemia. Those results demonstrate that KD can be a valuable therapeutic option for patients with RSE. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

  20. Is dengue severity related to nutritional status?

    PubMed

    Kalayanarooj, Siripen; Nimmannitya, Suchitra

    2005-03-01

    A retrospective review of dengue patients admitted to Queen Sirikit National Institute of Child Health (previously known as Children's Hospital) from 1995 to 1999 revealed 4,532 confirmed cases of dengue infection; 80.9% were dengue hemorrhagic fever (DHF) and 19.1% were dengue fever cases (DF). Among the DHF patients; 30.6% had shock. The majority of them, 66.6%, had a normal nutritional status, while 9.3% were malnourished and 24.2% had obesity as classified by weight for age. Compared with control patients with other diagnoses (excluding HIV/AIDS patients), malnourished children had a lower risk of contracting dengue infection (odds ratio = 0.48, 95% Cl = 0.39-0.60, p = 0.000) while obese children had a greater risk of infection with dengue viruses (odds ratio = 1.96, 95% Cl = 1.55-2.5, p = 0.000). The clinical signs, symptoms and laboratory findings of dengue were almost the same among the 3 groups of malnourished, normal, and obese patients. The minor differences observed were that in obese children liver enlargement was found less often; maculopapular/convalescence rash and elevations of alanine aminotransferase were found more often. Malnourished patients had a higher risk of developing shock (37.8%) than normal (29.9%) and obese patients (30.2%) (p = 0.000). Obese patients had more unusual presentations: encephalopathy (1.3%) and associated infections (4.8%), than normal (0.5% and 2.7%) and malnourished patients (1.2% and 3.1%). Complications of fluid overload were found more in obese patients (6.5%) compared to normal (3.2%) and malnourished patients (2.1%) (p = 0.000). The case-fatality rates (CFR) in malnourished patients and obese patients were 0.5% and 0.4%, respectively, while in normal patients the CFR was 0.07%. Under and over nutrition DHF patients had either a greater risk of shock or unusual presentations and complications, which can lead to severe disease or complications and probably a higher CFR.

  1. Interleukin-1 receptor is a target for adjunctive control of diazepam-refractory status epilepticus in mice.

    PubMed

    Xu, Zheng-Hao; Wang, Yi; Tao, An-Feng; Yu, Jie; Wang, Xiao-Yu; Zu, Yun-Yun; Zhang, Shi-Hong; Chen, Zhong

    2016-07-22

    Proinflammatory cytokine interleukin-1 beta (IL-1β) may accumulate in the brain during status epilepticus, but whether it contributes to the progressive refractoriness of SE remains unclear. By using a kainic acid-induced SE mice model, we tested whether pharmacological blockade or knock-out of interleukin-1 receptor type 1 (IL-1R1) could influence the diazepam-refractory phenomenon of prolonged SE. We confirmed diazepam failed to terminate prolonged SE (allowed to continue for 40min before diazepam administration). The expression level of IL-1β in the hippocampus during prolonged SE was significantly higher than that of baseline. Interestingly, prolonged SE was not diazepam-refractory in IL-1R1 knock-out mice. Moreover, administration of interleukin-1 receptor antagonist (IL-1RA) combined with diazepam terminated established prolonged SE, while IL-1RA alone is not capable to terminate prolonged SE. On the contrary, administration of recombinant human IL-1β weakens the efficacy of diazepam by prolonging its latency to terminate non-prolonged SE. Thus, the present study provides direct evidence that accumulated IL-1β contributed to the diazepam refractoriness of prolonged SE, and suggests that interleukin-1 receptor is a target for adjunctive control of diazepam-refractory SE. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Modulation of oxidative stress and microinflammatory status by colloids in refractory dialytic hypotension

    PubMed Central

    2011-01-01

    Background Intradialytic hypotension may adversely affect the outcome of chronic hemodialysis. Therapeutic albumin has powerful anti-oxidant and anti-inflammatory properties. We have recently shown that systematic colloid infusion during hemodialysis sessions improves hemodynamic parameters in most dialysis hypotension-prone patients unresponsive to usual of preventive measures. We postulated that frequent hypotensive episodes may lead to a noxious inflammatory response mediated by oxidative stress induced by ischemia-reperfusion. The aim of this study was therefore to analyze the effect of 20% albumin and 4% gelatin infusions on oxidative stress and microinflammatory status in hypotension-prone patients unresponsive to usual preventive measures. Methods Prospective cross-over study (lasting 20 weeks) of routine infusion of 200 ml of 20% albumin versus 200 ml of 4% gelatin in 10 patients with refractory intradialytic hypotension. We analyzed the effect of 20% albumin and 4% gelatin on microinflammatory status, oxidative stress, serum nitrite and nitrate levels by analysis of variance. Results A significant decrease in serum ceruloplasmin and serum C3 was observed during the albumin period (p < 0.05, repeated measure ANOVA). A significant decrease in serum hydrogen peroxide was seen during albumin and gelatin administration (p < 0.01, repeated measure ANOVA) and a very large decrease in serum lipid peroxides was observed during the albumin period only (p < 0.01, Friedman test). Serum lactoferrin, serum proinflammatory cytokines and serum nitrite and nitrate levels remained stable during the different periods of this pilot trial. Conclusions We conclude that the improvement in microinflammatory status observed during colloid infusion in hypotension-prone dialysis patients may be related to a decrease in ischemia-reperfusion of noble organs, together with a specific reduction in oxidative stress by albumin. Trial registration ISRCTN 20957055 PMID:22013952

  3. 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

  4. Lidocaine treatment in refractory status epilepticus resulting from febrile infection-related epilepsy syndrome: a case report and follow-up.

    PubMed

    Capizzi, Giorgio; Vittorini, Roberta; Torta, Francesca; Davico, Chiara; Rainò, Elena; Conio, Alessandra; Longobardo, Annalisa; Briatore, Eleonora; Podestà, Barbara; Calzolari, Stefano

    2015-02-01

    We report the management of refractory status epilepticus (SE) by using continuous intravenous infusions of lidocaine in a previously healthy 15-year-old girl with a "catastrophic encephalopathy" in whom a diagnosis of febrile infection-related epilepsy syndrome was supposed. One week after a banal pharyngitis and fever, the patient presented confusion and intractable clusters of seizures. Although she underwent multiple examinations investigating all possible etiologies (intracranial infection, autoimmune disease, or toxic and metabolic illness), all results were negative except a feeble positivity to Mycoplasma pneumoniae serum antibodies. SE was initially treated with benzodiazepine followed by administration of barbiturates and subsequent induction of coma because of refractory SE; different antiepileptic drugs (AEDs) were given at different times in a period of 6 weeks but clinical and electroencephalographic improvements were achieved only after continuous infusion of lidocaine. When she recovered from SE, the patient developed severe psychomotor and cognitive impairment associated with cerebral atrophy. Treatment with lidocaine or other alternative drugs in cases of prolonged SE should be taken into account as soon as it becomes clear that the clinical condition is refractory to common AEDs included in available guidelines for SE treatment, to improve the bad outcome of this severe condition, at least limiting the negative effects of prolonged high metabolic demand due to continuous epileptiform activity and/or the possible negative effects of prolonged burst-suppression coma. Georg Thieme Verlag KG Stuttgart · New York.

  5. 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.

  6. Measurements of Total Hemispherical Emissivity of Several Stably Oxidized Metals and Some Refractory Oxide Coatings

    NASA Technical Reports Server (NTRS)

    Wade, William R.

    1959-01-01

    A description of the apparatus and methods used for obtaining total hemispherical emissivity is presented, and data for several stably oxidized metals are included. The metals which were tested included type 347 stainless steel, tungsten, and Haynes alloys B, C, X, and 25. No values of emissivity were obtained for tungsten or Haynes alloy B because of the nature of the oxides produced. The refractory oxide coatings tested were flame-sprayed alumina and zirconia. The results of the investigation indicate that strongly adherent, oxidized surfaces of a high stable emissivity can be produced on type 347 stainless steel for which the total hemispherical emissivity varied from 0.87 to 0.91 for temperatures from 600 F to 2,000 F. For this same temperature range, the Haynes alloys tested showed values of total hemispherical emissivity from 0.90 to 0.96 for alloy C, from 0.85 to 0.88 for alloy X, and from 0.85 to 0.89 for alloy 25. Haynes alloy B and tungsten formed nonadherent oxides at elevated temperatures and, therefore, stable emissivities were not obtained. The results obtained for the flame-sprayed ceramics (alumina and zirconia) showed considerably higher values of total emissivity than those measured for coatings applied by other methods. Emissivity values ranging from 0.69 to 0.44 for aluminum oxide and from 0.62 to 0.44 for zirconium oxide were measured for temperatures from 800 F to 2,000 F.

  7. Bowel Ischemia in Refractory Status Epilepticus: Report of Two Cases and Review of the Literature.

    PubMed

    Rizek, P; Ikeda, K M; Mele, T; Garcia, B; Gofton, T E

    2016-02-01

    Bowel ischemia is a rare life threatening complication seen in patients with refractory status epilepticus (RSE). The few reported cases of bowel ischemia in this setting have been associated with the use continuous barbiturate infusions. We report two patients with RSE in the absence of barbiturate infusion and without clear structural, infectious, anatomic, vascular, or autoimmune etiology. We review the clinical details of the cases and potential factors involved in the development of non-occlusive bowel ischemia in patients with RSE. The following is a retrospective review of two cases of non-occlusive mesenteric ischemia that occurred during the management of RSE. The clinical data and the details of pathological examination of the infarcted segments of bowel are presented in both cases. In both cases, the bowel ischemia occurred in the absence of barbiturate infusion or evidence of clear thrombosis, infection, or autoimmune etiology. Case 1 had extensive ischemic necrosis of the small bowel with secondary pseudomembrane formation, and case 2 had full thickness infarction of both the large and small bowel. The mechanism of bowel infarction in these cases is likely multifactorial and was not associated with barbiturate use. Likely contributors to ischemia include RSE itself, systemic hypotension, vasopressor use, general anesthesia, and abnormal cardiac function. During the management of RSE, every effort must be made to avoid the secondary complications such as bowel ischemia.

  8. Successful Treatment of Refractory Status Epilepticus Using Anterior Thalamic Nuclei Deep Brain Stimulation.

    PubMed

    Lee, Ching-Yi; Lim, Siew-Na; Wu, Tony; Lee, Shih-Tseng

    2017-03-01

    Refractory status epilepticus (RSE) is considered a medical emergency in neurology and is related to high mortality. We report a successfully treated case of RSE using deep brain stimulation (DBS) at the anterior thalamic nuclei (ATN) in a 17-year-old woman. This patient developed RSE as a result of progressive seizure activity. RSE with generalized tonic-clonic seizures was noted 2 weeks before admission. Video electroencephalography monitoring showed continuous 3-Hz generalized spike-and-wave complexes with higher amplitude over bilateral frontal. Four weeks after RSE onset, bilateral DBS of the ATN was started. This treatment was immediately followed by the disappearance of tonic-clonic seizures and spike-and-wave complexes, suggesting resolution of the RSE. Significant clinical improvement was noted 1 week after DBS implantation. DBS at the ATN significantly improved both the electroencephalography and clinical presentation in the patient with RSE. DBS at the ATN should be considered as a possible treatment choice once a patient develops RSE. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Plasmapheresis for refractory status epilepticus, part I: A scoping systematic review of the adult literature.

    PubMed

    Zeiler, F A; Matuszczak, M; Teitelbaum, J; Kazina, C J; Gillman, L M

    2016-12-01

    Our goal was to perform a scoping systematic review of the literature on the use of plasmapheresis or plasma exchange (PE) for refractory status epilepticus (RSE) in adults. Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to May 2016), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. Twenty-two original articles were identified. Twenty-seven adult patients were described in these articles, with a variety of autoimmune conditions leading to RSE. Seizure response with the application of PE therapy occurred in 14 of the 27 patients (51.9%), with 1 (3.7%) and 13 (48.1%) displaying partial and complete responses respectively. Generalized RSE was the most likely seizure subtype to respond to PE therapy. One patient had recorded an adverse events related to PE therapy. Oxford level 4, GRADE D evidence exists to suggest an uncertain response of adult autoimmune RSE to PE therapy. Thus, the routine application of PE therapy for adult autoimmune RSE cannot be recommended at this time. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  10. Lacosamide in children with refractory status epilepticus. A multicenter Italian experience.

    PubMed

    Grosso, Salvatore; Zamponi, Nelia; Bartocci, Arnaldo; Cesaroni, Elisabetta; Cappanera, Silvia; Di Bartolo, Rosanna; Balestri, Paolo

    2014-09-01

    Status epilepticus (SE) is considered a life-threatening medical emergency. First-line treatment with antiepileptic drugs (AEDs) consists of intravenous benzodiazepines followed by phenytoin. SE is considered refractory (RSE) when unresponsive to standard doses of the first two AEDs. Scarce evidence is available to support specific guidelines for the management of RSE in either adults or children. This study aimed to assess the efficacy and tolerability of intravenous (iv) lacosamide (LCM) in children affected by RSE. Children with RSE who were treated with ivLCM were included in the study. Efficacy was defined as the cessation of seizures after administration of ivLCM, with no need for any further antiepileptic drug. All patients had been unsuccessfully treated following standard protocols before ivLCM was administered. Eleven children entered the study (mean age: 9.4 years). Etiology was symptomatic in 7 patients (63%). RSE was convulsive (focal or generalized) in 6 patients and nonconvulsive in 5. The mean initial bolus dose of LCM was 8.6 mg/kg. The drug, which was used as a fourth or later option, was effective in stopping RSE in 45% of patients, with seizures terminating within 12 h in three children. No serious adverse events attributable to LCM were reported. LCM might be an effective and well-tolerated AED in children with RSE. Copyright © 2014. Published by Elsevier Ltd.

  11. Propofol and barbiturates for the anesthesia of refractory convulsive status epilepticus: pros and cons.

    PubMed

    Parviainen, Ilkka; Kälviäinen, Reetta; Ruokonen, Esko

    2007-10-01

    To discuss mainly the use of propofol and barbiturates in the anesthesia of refractory status epilepticus (RSE). Review of literature. There are no prospective, randomized works comparing the effects of anesthetics in the treatment of RSE. Recently, the use of propofol has increased in the treatment of RSE. Propofol terminates both clinical and electric seizures quickly, but the maintenance of burst-suppression EEG pattern requires repetitive titration of doses. Relapses of seizures have occurred in 19-33% of patients, especially when tapering of dose. The advantages of barbiturates are lower frequency of short-term treatment failures, breakthrough seizures and changes to a different anesthetic agent. On the other hand, prolonged recovery leads to prolonged duration of mechanical ventilation, intensive care and hospital stay. The use of propofol, barbiturates or midazolam in the anesthesia of RSE can be justified. When using propofol, the duration of high doses should be limited to 48 hours and the risk of propofol infusion syndrome should be kept in mind. High doses of barbiturates terminate effectively seizures but recovery from anesthesia prolongs ventilator treatment and intensive care.

  12. Survey of the diagnostic and therapeutic approach to new-onset refractory status epilepticus.

    PubMed

    Cabrera Kang, Christian M; Gaspard, Nicolas; LaRoche, Suzette M; Foreman, Brandon

    2017-03-01

    We conducted a survey of providers to assess for practice patterns in diagnosing and treating new-onset refractory status epilepticus (NORSE). NORSE is the occurrence of prolonged seizures that are not responsive to initial therapies in otherwise healthy individuals without obvious cause on initial presentation. This entity is thought to have multiple etiologies, including autoimmune. A 29-question electronic survey was sent to providers included in the Neurocritical Care Society emailing list. Questions regarded responders' demographics, existing institutional practice protocols, diagnostic work-up, therapeutic management and expected outcomes in NORSE. Responses were collected from October 23, 2014, to November 25, 2014. There were 107 respondents out of 1334 (8%). CT head, continuous EEG, lumbar puncture and microbe serologies were suggested within 24h of presentation as part of a diagnostic work-up. MRI brain, autoimmune work-up (systemic and anti-neuronal antibodies) and cytology/flow cytometry were favored later in the course. About 25% of providers would never perform an autoimmune work-up in this setting. Initial treatment included up to 3 anticonvulsants (including one anesthetic), followed by additional anticonvulsants/anesthetics along with antimicrobials, followed by steroids, plasma exchange, hypothermia and ketogenic diet. Many respondents would never use IV immunoglobulin or steroid-sparing immunosuppressants (29% and 42%, respectively) for NORSE. This survey could serve as the foundation for development of a standardized approach for the diagnosis and treatment of NORSE. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  13. Plasmapheresis for refractory status epilepticus Part II: A scoping systematic review of the pediatric literature.

    PubMed

    Zeiler, F A; Matuszczak, M; Teitelbaum, J; Kazina, C J; Gillman, L M

    2016-12-01

    Our goal was to perform a scoping systematic review of the literature on the use of plasmapheresis or plasma exchange (PE) for refractory status epilepticus (RSE) in children. Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to May 2016), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. Twenty-two original articles were identified, with 37 pediatric patients. The mean age of the patients was 8.3 years (age median: 8.5, range: 0.6 years-17 years). Seizure response to PE therapy occurred in 9 of the 37 patients (24.3%) included in the review, with 7 patients (18.9%) displaying resolution of seizures and 2 patients (5.4%) displaying a partial reduction in seizure volume. Twenty-eight of the 37 patients (75.7%) had no response to PE therapy. No adverse events were recorded. Oxford level 4, GRADE D evidence exists to suggest little to no benefit of PE in pediatric RSE. Routine application of PE for pediatric RSE cannot be recommended at this time. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  14. 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.

  15. Fecal Microbiota Transplantation Using Upper Gastrointestinal Tract for the Treatment of Refractory or Severe Complicated Clostridium difficile Infection in Elderly Patients in Poor Medical Condition: The First Study in an Asian Country

    PubMed Central

    Gweon, Tae-Geun; Kim, Jinsu; Lim, Chul-Hyun; Park, Jae Myung; Lee, Dong-Gun; Lee, In Seok; Cho, Young-Seok; Kim, Sang Woo; Choi, Myung-Gyu

    2016-01-01

    Background and Aims. Fecal microbiota transplantation (FMT) is a highly effective treatment option for refractory Clostridium difficile infection (CDI). FMT may be challenging in patients with a low performance status, because of their poor medical condition. The aims of this study were to describe our experience treating patients in poor medical condition with refractory or severe complicated CDI using FMT via the upper GI tract route. Methods. This study was a retrospective review of seven elderly patients with refractory or severe complicated CDI and a poor medical condition who were treated with FMT through the upper GI tract route from May 2012 through August 2013. The outcomes studied included the cure rate of CDI and adverse events. Results. Of these seven patients who received FMT via the upper GI tract route, all patients were cured. During the 11-month follow-up period, CDI recurrence was observed in two patients; rescue FMT was performed in these patients, which led to a full cure. Vomiting was observed in two patients. Conclusions. FMT via the upper gastrointestinal tract route may be effective for the treatment of refractory or severe complicated CDI in patients with a low performance status. Physicians should be aware of adverse events, especially vomiting. PMID:27127501

  16. Ketamine in refractory convulsive status epilepticus in children avoids endotracheal intubation.

    PubMed

    Ilvento, Lucrezia; Rosati, Anna; Marini, Carla; L'Erario, Manuela; Mirabile, Lorenzo; Guerrini, Renzo

    2015-08-01

    The purpose of this study was to report on the efficacy and safety of intravenous ketamine (KE) in refractory convulsive status epilepticus (RCSE) in children and highlight its advantages with particular reference to avoiding endotracheal intubation. Since November 2009, we have used a protocol to treat RCSE including intravenous KE in all patients referred to the Neurology Unit of the Meyer Children's Hospital. From November 2009 to February 2015, 13 children (7 females; age: 2 months-11 years and 5 months) received KE. Eight patients were treated once, two were treated twice, and the remaining three were treated 3 times during different RCSE episodes, for a total of 19 treatments. Most of the RCSE episodes were generalized (14/19). A malformation of cortical development was the most frequent etiology (4/13 children). Ketamine was administered from a minimum of 22 h to a maximum of 17 days, at doses ranging from 7 to 60 mcg/kg/min, obtaining a resolution of the RCSE in 14/19 episodes. Five patients received KE in lieu of conventional anesthetics, thus, avoiding endotracheal intubation. Ketamine was effective in 4 of them. Suppression-burst pattern was observed after the initial bolus of 3mg/kg in the majority of the responder RCSE episodes (10/14). Ketamine is effective in treating RCSE and represents a practical alternative to conventional anesthetics for the treatment of RCSE. Its use avoids the pitfalls and dangers of endotracheal intubation, which is known to worsen RCSE prognosis. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Prognosis and predictors of outcome of refractory generalized convulsive status epilepticus in adults treated in neurointensive care unit.

    PubMed

    Vooturi, Sudhindra; Jayalakshmi, Sita; Sahu, Sambit; Mohandas, Surath

    2014-11-01

    To evaluate the etiological profile, clinical characteristics and outcome of patients with refractory generalized convulsive status epilepticus treated in Neurological Intensive Care Unit (NICU). In this open cohort study, data of 126 patients, aged 18 years and above, with convulsive status epilepticus (SE) admitted in NICU was collected. Status epilepticus was defined as seizures lasting for more than five minutes without regaining consciousness. Refractory SE (RSE) was defined as SE refractory to 2 antiepileptic drugs and requiring anesthetic agents for seizure control. Survival and regression analysis were done to analyze the outcome and factors predicting outcome respectively in the study population. Out of 126 patients, 81 patients had non -refractory status epilepticus (NRSE); 45 (35.7%) had RSE. Acute symptomatic etiology was noted in 58.6% of entire cohort. Significantly higher percentage of patients with RSE had an etiology of CNS infections than NRSE group (44.4% vs. 23.5%; P=0.0171). Amongst the CNS infections, viral encephalitis was significantly higher in RSE than NRSE patients (31% vs. 6.2%; P=0.0004). All the patients with RSE required mechanical ventilation. Overall mortality was 19%. The mortality in RSE was 42% (19 out of 45), significantly higher when compared to NRSE where only 6% (5 out of 81) died. On logistic regression, the only predictor of death was fever with an odds ratio of 8.55 (P=0.024). CNS infections, especially viral encephalitis and complications of mechanical ventilation were significantly higher in adult RSE patients. Although mortality is higher in adult patients with RSE, etiology does not contribute to mortality; however fever predicts mortality in these patients. Aggressive management of underlying etiology and prevention of systemic complications may improve outcome in adult RSE patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Severe repetitive exercise and haematological status.

    PubMed Central

    Ross, J. H.; Attwood, E. C.

    1984-01-01

    The effects of severe repetitive exercise on certain haematological measurements were studied. Decreases in haematocrit and haemoglobin (13% in one group of participants) took place during the first 2 weeks but not the third week of increasingly severe exertion and the reasons for this are discussed. Haemolysis probably plays only a small part and plasma volume expansion is likely to be the main cause of this phenomenon. It is suggested that there is no stimulus for the haemoglobin concentration to be increased to match the increased plasma volume as tissue oxygen tension is maintained satisfactorily. PMID:6462992

  19. Therapeutic Efficacy of Fresh, Autologous Mesenchymal Stem Cells for Severe Refractory Gingivostomatitis in Cats

    PubMed Central

    Mills-Ko, Emily; Verstraete, Frank J.M.; Kol, Amir; Walker, Naomi J.; Badgley, Megan R.; Fazel, Nasim; Murphy, William J.; Vapniarsky, Natalia; Borjesson, Dori L.

    2016-01-01

    Mesenchymal stem cells (MSCs) are a promising therapy for immune-mediated and inflammatory disorders, because of their potent immunomodulatory properties. In this study, we investigated the use of fresh, autologous, adipose-derived MSCs (ASCs) for feline chronic gingivostomatitis (FCGS), a chronic, debilitating, idiopathic, oral mucosal inflammatory disease. Nine cats with refractory FCGS were enrolled in this pilot study. Each cat received 2 intravenous injections of 20 million autologous ASCs, 1 month apart. Oral biopsies were taken before and at 6 months after the first ASC injection. Blood immune cell subsets, serum protein, and cytokine levels were measured at 0, 1, 3, and 6 months after treatment to assess immunomodulatory effects. Seven of the 9 cats completed the study. Five cats responded to treatment by either complete clinical remission (n = 3) or substantial clinical improvement (n = 2). Two cats were nonresponders. Cats that responded to treatment also exhibited systemic immunomodulation demonstrated by decreased numbers of circulating CD8+ T cells, a normalization of the CD4/CD8 ratio, decreased neutrophil counts, and interferon-γ and interleukin (IL)-1β concentration, and a temporary increase in serum IL-6 and tumor necrosis factor-α concentration. No clinical recurrence has occurred following complete clinical remission (follow-up of 6–24 months). In this study, cats with <15% cytotoxic CD8 T cells with low expression of CD8 (CD8lo) cells were 100% responsive to ASC therapy, whereas cats with >15% CD8lo cells were nonresponders. The relative absence of CD8lo cells may be a biomarker to predict response to ASC therapy, and may shed light on pathogenesis of FCGS and mechanisms by which ASCs decrease oral inflammation and affect T-cell phenotype. Significance This study is the first to demonstrate the safety and efficacy of fresh, autologous, adipose-derived stem cell systemic therapy for a naturally occurring, chronic inflammatory disease in cats

  20. Therapeutic Efficacy of Fresh, Autologous Mesenchymal Stem Cells for Severe Refractory Gingivostomatitis in Cats.

    PubMed

    Arzi, Boaz; Mills-Ko, Emily; Verstraete, Frank J M; Kol, Amir; Walker, Naomi J; Badgley, Megan R; Fazel, Nasim; Murphy, William J; Vapniarsky, Natalia; Borjesson, Dori L

    2016-01-01

    Mesenchymal stem cells (MSCs) are a promising therapy for immune-mediated and inflammatory disorders, because of their potent immunomodulatory properties. In this study, we investigated the use of fresh, autologous, adipose-derived MSCs (ASCs) for feline chronic gingivostomatitis (FCGS), a chronic, debilitating, idiopathic, oral mucosal inflammatory disease. Nine cats with refractory FCGS were enrolled in this pilot study. Each cat received 2 intravenous injections of 20 million autologous ASCs, 1 month apart. Oral biopsies were taken before and at 6 months after the first ASC injection. Blood immune cell subsets, serum protein, and cytokine levels were measured at 0, 1, 3, and 6 months after treatment to assess immunomodulatory effects. Seven of the 9 cats completed the study. Five cats responded to treatment by either complete clinical remission (n=3) or substantial clinical improvement (n=2). Two cats were nonresponders. Cats that responded to treatment also exhibited systemic immunomodulation demonstrated by decreased numbers of circulating CD8+ T cells, a normalization of the CD4/CD8 ratio, decreased neutrophil counts, and interferon-γ and interleukin (IL)-1β concentration, and a temporary increase in serum IL-6 and tumor necrosis factor-α concentration. No clinical recurrence has occurred following complete clinical remission (follow-up of 6-24 months). In this study, cats with <15% cytotoxic CD8 T cells with low expression of CD8 (CD8lo) cells were 100% responsive to ASC therapy, whereas cats with >15% CD8lo cells were nonresponders. The relative absence of CD8lo cells may be a biomarker to predict response to ASC therapy, and may shed light on pathogenesis of FCGS and mechanisms by which ASCs decrease oral inflammation and affect T-cell phenotype. This study is the first to demonstrate the safety and efficacy of fresh, autologous, adipose-derived stem cell systemic therapy for a naturally occurring, chronic inflammatory disease in cats. The findings

  1. The cost of treating severe refractory asthma in the UK: an economic analysis from the British Thoracic Society Difficult Asthma Registry.

    PubMed

    O'Neill, Stephen; Sweeney, Joan; Patterson, Chris C; Menzies-Gow, Andrew; Niven, Rob; Mansur, Adel H; Bucknall, Christine; Chaudhuri, Rekha; Thomson, Neil C; Brightling, Chris E; O'Neill, Ciaran; Heaney, Liam G

    2015-04-01

    Severe refractory asthma poses a substantial burden in terms of healthcare costs but relatively little is known about the factors which drive these costs. This study uses data from the British Thoracic Society Difficult Asthma Registry (n=596) to estimate direct healthcare treatment costs from an National Health Service perspective and examines factors that explain variations in costs. Annual mean treatment costs among severe refractory asthma patients were £2912 (SD £2212) to £4217 (SD £2449). Significant predictors of costs were FEV1% predicted, location of care, maintenance oral corticosteroid treatment and body mass index. Treating individuals with severe refractory asthma presents a substantial cost to the health service.

  2. Liver Transplantation as a Treatment for Severe Refractory Vitamin E Deficiency Related to Progressive Familial Intrahepatic Cholestasis Type 2 in a Pediatric Patient.

    PubMed

    Collyer, Elizabeth; Hupertz, Vera; Eghtesad, Bijan; Radhakrishnan, Kadakkal

    2016-08-01

    Refractory vitamin E deficiency is thought to have irreversible effects on neurologic function. We report an adolescent boy with severe refractory vitamin E deficiency due to progressive familial intrahepatic cholestasis (PFIC) type 2. His consequent neurologic dysfunction included severe ataxia, dysmetria, dysarthria, and cranial nerve VI palsy. He underwent liver transplantation at age 13 due to his neurologic dysfunction; and afterward, he had marked improvement in neurologic function. We demonstrate that in a patient with PFIC 2 and severe refractory vitamin E deficiency, liver transplant can improve vitamin E absorption, prevent further neurological sequelae, and reverse prior neurologic dysfunction.

  3. Liver Transplantation as a Treatment for Severe Refractory Vitamin E Deficiency Related to Progressive Familial Intrahepatic Cholestasis Type 2 in a Pediatric Patient

    PubMed Central

    Hupertz, Vera; Eghtesad, Bijan; Radhakrishnan, Kadakkal

    2016-01-01

    Refractory vitamin E deficiency is thought to have irreversible effects on neurologic function. We report an adolescent boy with severe refractory vitamin E deficiency due to progressive familial intrahepatic cholestasis (PFIC) type 2. His consequent neurologic dysfunction included severe ataxia, dysmetria, dysarthria, and cranial nerve VI palsy. He underwent liver transplantation at age 13 due to his neurologic dysfunction; and afterward, he had marked improvement in neurologic function. We demonstrate that in a patient with PFIC 2 and severe refractory vitamin E deficiency, liver transplant can improve vitamin E absorption, prevent further neurological sequelae, and reverse prior neurologic dysfunction. PMID:28119944

  4. Intravenous ketamine for the treatment of refractory status epilepticus: a retrospective multi-center study

    PubMed Central

    Gaspard, Nicolas; Foreman, Brandon; Judd, Lilith M.; Brenton, James N.; Nathan, Barnett R.; McCoy, Blathnaid M.; Al-Otaibi, Ali; Kilbride, Ronan; Fernández, Ivan Sánchez; Mendoza, Lucy; Samuel, Sophie; Zakaria, Asma; Kalamangalam, Giridhar P.; Legros, Benjamin; Szaflarski, Jerzy P.; Loddenkemper, Tobias; Hahn, Cecil D.; Goodkin, Howard P.; Claassen, Jan; Hirsch, Lawrence J.; LaRoche, Suzette M.

    2013-01-01

    Summary Purpose To examine patterns of use, efficacy and safety of intravenous ketamine for the treatment of refractory status epilepticus (RSE). Methods Multicenter retrospective review of medical records and EEG reports in ten academic medical centers in North America and Europe, including 58 subjects, representing 60 episodes of RSE were identified between 1999 and 2012. Seven episodes occurred after anoxic brain injury. Key findings Permanent control of RSE was achieved in 57% (34/60) of episodes. Ketamine was felt to have contributed to permanent control (“possible” or “likely” responses) in 32% (19/60) including seven (12%) in which ketamine was the last drug added (likely responses). Four of the seven likely responses, but none of the 12 possible ones, occurred in patients with post-anoxic brain injury. No likely responses were observed when infusion rates were lower than 0.9mg/kg/h; when ketamine was introduced at least eight days after SE onset; or after failure of seven or more drugs. Ketamine was discontinued due to possible adverse events in five patients. Complications were mostly attributed to concurrent drugs, especially other anesthetics. Mortality rate was 43% (26/60), but was lower when SE was controlled within 24h of ketamine initiation (16% vs. 56%, p=0.0047). Significance Ketamine appears to be a relatively effective and safe drug for the treatment of RSE. This retrospective series provides preliminary data on effective dose and appropriate time of intervention to aid in the design of a prospective trial to further define the role of ketamine in the treatment of RSE. PMID:23758557

  5. The efficacy of topiramate in adult refractory status epilepticus: experience of a tertiary care center.

    PubMed

    Synowiec, Andrea S; Yandora, Kristin A; Yenugadhati, Vamsi; Valeriano, James P; Schramke, Carol J; Kelly, Kevin M

    2012-02-01

    Refractory status epilepticus (RSE) occurs in patients with SE when they fail to respond to traditional medical therapy. Because there are very few case reports of topiramate (TPM) treatment of RSE in adult patients, we examined our experience with TPM with regard to its safety and efficacy in seizure termination in RSE in an adult patient population. We report a retrospective review of 35 adult patients with RSE who were treated with TPM in addition to other antiepileptic drugs (AEDs) between 2003 and 2010. After failure of initial treatments of benzodiazepines and weight-based intravenous loading doses of standard AEDs, TPM tablets were crushed and administered via nasogastric tube. Data were collected on age, gender, history of epilepsy, etiology of RSE, daily dose of TPM, co-therapeutic agents, treatment response, and disposition. Following initiation of TPM use and discontinuation of continuous intravenous anesthetics with no additional AEDs administered, cumulative cessation of RSE in patients was 4/35 (11%) at one day, 10/35 (29%) at two days, and 14/35 (40%) at three days. However, when including all patients and comparing the two patient groups in which RSE was or was not terminated within three days of initiating TPM as the last or not last AED given, there was no significant difference. Time to TPM response was not associated with the type of seizures, etiology of SE, or whether there was a history of epilepsy. There were no documented side effects or complications of therapy with TPM. This study provides support for the use of TPM as an adjunctive agent in the treatment of RSE. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Feasibility Study Evaluating Therapeutic Hypothermia for Refractory Status Epilepticus in Children.

    PubMed

    Buttram, Sandra D W; Au, Alicia K; Koch, Joshua; Lidsky, Karen; McBain, Kristin; O'Brien, Nicole; Zielinski, Brandon A; Bell, Michael J

    2015-12-01

    Pediatric refractory status epilepticus (RSE) is a neurological emergency with significant morbidity and mortality, which lacks consensus regarding diagnosis and treatment(s). Therapeutic hypothermia (TH) is an effective treatment for RSE in preclinical models and small series. In addition, TH is a standard care for adults after cardiac arrest and neonates with hypoxic-ischemic encephalopathy. The purpose of this study was to identify the feasibility of a study of pediatric RSE within a research group (Pediatric Neurocritical Care Research Group [PNCRG]). Pediatric intensive care unit (PICU) admissions at seven centers were prospectively screened from October 2012 to July 2013 for RSE. Experts within the PNCRG estimated that clinicians would be unwilling to enroll a child, unless the child required at least two different antiepileptic medications and a continuous infusion of another antiepileptic medication with ongoing electrographic seizure activity for ≥2 hours after continuous infusion initiation. Data for children meeting the above inclusion criteria were collected, including the etiology of RSE, history of epilepsy, and maximum dose of continuous antiepileptic infusions. There were 8113 PICU admissions over a cumulative 52 months (October 2012-July 2013) at seven centers. Of these, 69 (0.85%) children met inclusion criteria. Twenty children were excluded due to acute diagnoses affected by TH, contraindications to TH, or lack of commitment to aggressive therapies. Sixteen patients had seizure cessation within 2 hours, resulting in 33 patients who had inadequate seizure control after 2 hours and a continuous antiepileptic infusion. Midazolam (21/33, 64%) and pentobarbital (5/33, 15%) were the most common infusions with a wide maximum dose range. More than one infusion was required for seizure control in four patients. There are substantial numbers of subjects at clinical sites within the PNCRG with RSE that would meet the proposed inclusion criteria for a

  7. 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.

  8. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol.

    PubMed

    Shorvon, Simon; Ferlisi, Monica

    2011-10-01

    Super-refractory status epilepticus is defined as status epilepticus that continues or recurs 24 h or more after the onset of anaesthetic therapy, including those cases where status epilepticus recurs on the reduction or withdrawal of anaesthesia. It is an uncommon but important clinical problem with high mortality and morbidity rates. This article reviews the treatment approaches. There are no controlled or randomized studies, and so therapy has to be based on clinical reports and opinion. The published world literature on the following treatments was critically evaluated: anaesthetic agents, anti-epileptic drugs, magnesium infusion, pyridoxine, steroids and immunotherapy, ketogenic diet, hypothermia, emergency resective neurosurgery and multiple subpial transection, transcranial magnetic stimulation, vagal nerve stimulation, deep brain stimulation, electroconvulsive therapy, drainage of the cerebrospinal fluid and other older drug therapies. The importance of treating the identifying cause is stressed. A protocol and flowchart for managing super-refractory status epilepticus is suggested. In view of the small number of published reports, there is an urgent need for the establishment of a database of outcomes of individual therapies.

  9. Safety and efficacy of intravenous lacosamide for adjunctive treatment of refractory status epilepticus: a comparative cohort study.

    PubMed

    Sutter, Raoul; Marsch, Stephan; Rüegg, Stephan

    2013-04-01

    Refractory status epilepticus (RSE) is an emergency with high mortality requiring neurointensive care. Treatment paradigms include first-generation antiepileptic drugs (AEDs) and anesthetics. Lacosamide (LCM) is a new AED, holding promise as a potent treatment option for RSE. High-level evidence regarding safety and efficacy in the treatment of RSE is lacking. The objective of the study was to evaluate the safety profile and efficacy of intravenous (i.v.) LCM as an add-on treatment in adult RSE patients. All consecutive RSE patients treated in the intensive care units (ICUs) of an academic tertiary care center between 2005 and 2011 were included. Severity of status epilepticus (SE) was graded by the SE Severity Scale (STESS), and SE etiology was categorized according to the guidelines of the International League Against Epilepsy (ILAE). Outcomes were seizure control, RSE duration, and death. Of 111 RSE patients, 53 % were treated with LCM. Twenty-five patients with hypoxic-ischemic encephalopathy were excluded. Mortality was 30 %. Mean number of AEDs, duration, severity, and etiology of SE, as well as critical medical conditions did not differ between patients with and without LCM. While age tended to be higher, critical interventions, such as the use of anesthetics and mechanical ventilation, tended to be less frequent in patients with LCM. Seizure control tended to be achieved more frequently in patients with LCM (odds ratio, OR 2.34, 95 % CI 0.5-10.1, p = 0.252). Among patients with LCM, 51 % received LCM as the last AED (including hypoxic-ischemic encephalopathy), allowing the reasonable assumption that LCM was responsible for seizure control, which was achieved in 91 %. Multivariable analysis revealed a decreased mortality in patients with LCM (OR 0.34, 95 % CI 0.1-0.9, p = 0.035). A possible confounder in this context was the implementation of continuous video-electroencephalography (EEG) monitoring 6 months prior to the first use of i.v. LCM. There were no

  10. 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

  11. Remission of refractory pyoderma gangrenosum, severe acne, and hidradenitis suppurativa (PASH) syndrome using targeted antibiotic therapy in 4 patients.

    PubMed

    Join-Lambert, Olivier; Duchatelet, Sabine; Delage, Maïa; Miskinyte, Snaigune; Coignard, Hélène; Lemarchand, Nicolas; Alemy-Carreau, Murielle; Lortholary, Olivier; Nassif, Xavier; Hovnanian, Alain; Nassif, Aude

    2015-11-01

    Pyoderma gangrenosum, severe acne, and suppurative hidradenitis (PASH) syndrome can prove refractory to treatment and is characterized by relapses and recurrences. The combination of antibiotic therapy and surgery can produce success in the management of the syndrome. Acute treatment is required, but maintenance therapy is also necessary to prevent disease relapse. The response to antibiotic therapy is hypothesis generating, raising the issue of a modified host response. To date, anecdotal reports support the use of surgery and medical therapy, but controlled investigations with extended follow-up are necessary to substantiate preliminary data observed with individual cases.

  12. [Current status of treatment of refractory ascites in patients with liver cirrhosis].

    PubMed

    Shao, J; Zhang, L; Han, G H; Fan, D M

    2016-10-20

    Ascites is a common clinical manifestation of cirrhotic portal hypertension, and about 60%-80% of cirrhotic patients develop the symptom of ascites within 10 years. Once ascites occurs, the 5-year survival rate is reduced from 80% to 50%. With the progression of liver diseases, approximately 5%-10% of patients with ascites develop refractory ascites, and the median survival time is only 6-12 months. This article reviews the definition and diagnosis of refractory ascites, evaluation of prognostic factors, and treatment regimens, including large-volume paracentesis combined with protein supplementation, transjugular intrahepatic portosystemic shunt, and liver transplantation.

  13. 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.

  14. Severe and refractory peptic ulcer disease: the diagnostic dilemma: case report and comprehensive review.

    PubMed

    Guzzo, James L; Duncan, Mona; Bass, Barbara L; Bochicchio, Grant V; Napolitano, Lena M

    2005-11-01

    The recognition of Helicobacter pylori infection as a cause of peptic ulcer disease, medical regimens to eradicate the organism, and the widespread use of proton pump inhibition to suppress gastric acid secretion have revolutionized the management of peptic ulcer disease. As a result, successful medical management of peptic ulcer disease has largely supplanted the need for gastric surgery by general surgeons. Surgery is reserved for complications of the disease, refractory disease, or rare causes of ulcer disease such as gastrinoma and Zollinger-Ellison syndrome. In this report, we describe a case of intractable peptic ulcer disease that progressed to gastric outlet obstruction despite maximal medical therapy. We review the diagnostic studies utilized to evaluate the potential etiologies of peptic ulcer disease and the difficulty in diagnosing gastrinoma and Zollinger-Ellison in the setting of potent medical acid suppression therapy.

  15. Refractory epilepsy is highly associated with severe dentoalveolar and maxillofacial injuries.

    PubMed

    Costa, Andre Luiz F; Yasuda, Clarissa Lin; França, Marcondes C; Morita, Marcia Elisabete; Cendes, Fernando

    2011-03-01

    Dental intrusion and avulsion, crown fracture and mandibular fractures are important dentofacial complications in patients with epilepsy-related traumas. The objective of the present study was to describe the occurrence of orofacial injuries in patients with epilepsy. One hundred and nine consecutive patients (60 women; mean age 38.81 ± 14 years), treated for refractory epilepsy (45 with extratemporal epilepsy and 64 with temporal epilepsy) at the outpatient clinic of our University Hospital, were included in the present study. Orofacial injury occurring as a direct result of a seizure was determined by clinical examination and interview. In addition, seizure frequency, use of medication, and the occurrence and type of injury to other parts of the body, were documented. We employed regression analyses to investigate the association between teeth fractures and frequency of seizures. The majority of injuries were crown fractures (42 subjects), followed by mandibular fractures (eight subjects) and tooth avulsion (eight subjects). Sixteen patients had more than two fractured teeth. Patients with mandibular trauma also suffered concomitant injuries (teeth fracture, avulsion and dislocation). The number of fractured teeth was associated with seizure frequency (r(2) = 0.59, p < 0.001). The data suggest that there is an increased rate of dentoalveolar and maxillofacial injuries in patients with poorly controlled epileptic seizures.

  16. MR enteroclysis in refractory celiac disease: proposal and validation of a severity scoring system.

    PubMed

    Van Weyenberg, Stijn J B; Meijerink, Martijn R; Jacobs, Maarten A J M; van Kuijk, Cornelis; Mulder, Chris J; van Waesberghe, Jan Hein T M

    2011-04-01

    To determine magnetic resonance (MR) enteroclysis findings in patients with uncomplicated celiac disease (CD), refractory CD (RCD) type I, and RCD type II, to develop and validate a scoring system to identify patients with RCD II and to determine the diagnostic accuracy of MR enteroclysis to detect CD-related malignancies. This study was performed with approval of the institutional review board. One radiologist blinded to clinical details retrospectively evaluated quantitative and qualitative criteria of 28 studies obtained in symptomatic patients with CD (uncomplicated CD, n = 10; RCD I, n = 8; RCD II, n = 10). A scoring system was developed by using parameters identified in multivariate analysis to be associated with RCD II, which two radiologists evaluated in a second group of 40 symptomatic patients with CD. Accuracy to detect malignancy was assessed in the total study group. Cumulative survival was evaluated in the total study group by using the Kaplan-Meier method. MR enteroclysis could not be used to discriminate between uncomplicated CD and RCD I. The presence of less than 10 folds per 5 cm jejunum, mesenteric fat infiltration, and bowel wall thickening were associated with RCD II. A positive MR score was defined as the presence of two or more of these features. In the validation group, the MR score was positive in 13 of 15 patients with RCD II (sensitivity, 0.87) and negative in 24 of 25 patients without RCD II (specificity, 0.96). The 5-year survival rate was 95% in patients with a negative MR score and 56% in patients with a positive MR score (P < .0001). MR enteroclysis helped to identify the presence of seven of eight malignancies and to diagnose absence of malignancy in 58 of 60 studies. MR enteroclysis can be used to investigate the presence of RCD II or malignancy in symptomatic patients with CD. © RSNA, 2011.

  17. Medium to long-term efficacy and safety of oral tacrolimus in moderate to severe steroid refractory ulcerative colitis.

    PubMed

    Olmedo Martín, Raúl Vicente; Amo Trillo, Víctor; González Grande, Rocío; Jiménez Pérez, Miguel

    2017-08-01

    Oral tacrolimus is an effective drug that induces clinical remission in patients with moderate to severe ulcerative colitis refractory to steroids. However, there is little data with regard to its medium to long-term efficacy and safety. The aim of this study was to assess the medium to long-term efficacy and safety of oral tacrolimus in this challenging clinical situation. This was a retrospective observational review of the clinical charts of 34 patients with moderate to severe ulcerative colitis refractory to steroids treated with oral tacrolimus at our hospital (July 2001-July 2016). Remission was defined as a Lichtiger index score < 3 and response was defined as a score < 10 with a reduction of at least three points compared to the baseline score. Seven patients (20.58%) required colectomy during the follow-up period (mean 65 months). Nine patients required rescue with infliximab (four patients during the first six months of follow-up and the other five after the first six months). The short to medium clinical efficacy combining both remission and clinical response was 82% at six months. Kaplan-Meier analysis showed that the percentage of patients free from colectomy and additional sequential rescue therapy was 75% at 54 months (median follow-up). The early introduction of thiopurines (< 2 months from start of tacrolimus) showed no significant improvement in prognosis (p = 0.72). Fifty-three per cent of patients experienced adverse effects, none of whom required treatment withdrawal. No severe infections were noted during the follow-up.

  18. Statistical Cluster Analysis of the British Thoracic Society Severe Refractory Asthma Registry: Clinical Outcomes and Phenotype Stability

    PubMed Central

    Newby, Chris; Heaney, Liam G.; Menzies-Gow, Andrew; Niven, Rob M.; Mansur, Adel; Bucknall, Christine; Chaudhuri, Rekha; Thompson, John; Burton, Paul; Brightling, Chris

    2014-01-01

    Background Severe refractory asthma is a heterogeneous disease. We sought to determine statistical clusters from the British Thoracic Society Severe refractory Asthma Registry and to examine cluster-specific outcomes and stability. Methods Factor analysis and statistical cluster modelling was undertaken to determine the number of clusters and their membership (N = 349). Cluster-specific outcomes were assessed after a median follow-up of 3 years. A classifier was programmed to determine cluster stability and was validated in an independent cohort of new patients recruited to the registry (n = 245). Findings Five clusters were identified. Cluster 1 (34%) were atopic with early onset disease, cluster 2 (21%) were obese with late onset disease, cluster 3 (15%) had the least severe disease, cluster 4 (15%) were the eosinophilic with late onset disease and cluster 5 (15%) had significant fixed airflow obstruction. At follow-up, the proportion of subjects treated with oral corticosteroids increased in all groups with an increase in body mass index. Exacerbation frequency decreased significantly in clusters 1, 2 and 4 and was associated with a significant fall in the peripheral blood eosinophil count in clusters 2 and 4. Stability of cluster membership at follow-up was 52% for the whole group with stability being best in cluster 2 (71%) and worst in cluster 4 (25%). In an independent validation cohort, the classifier identified the same 5 clusters with similar patient distribution and characteristics. Interpretation Statistical cluster analysis can identify distinct phenotypes with specific outcomes. Cluster membership can be determined using a classifier, but when treatment is optimised, cluster stability is poor. PMID:25058007

  19. Statistical cluster analysis of the British Thoracic Society Severe refractory Asthma Registry: clinical outcomes and phenotype stability.

    PubMed

    Newby, Chris; Heaney, Liam G; Menzies-Gow, Andrew; Niven, Rob M; Mansur, Adel; Bucknall, Christine; Chaudhuri, Rekha; Thompson, John; Burton, Paul; Brightling, Chris

    2014-01-01

    Severe refractory asthma is a heterogeneous disease. We sought to determine statistical clusters from the British Thoracic Society Severe refractory Asthma Registry and to examine cluster-specific outcomes and stability. Factor analysis and statistical cluster modelling was undertaken to determine the number of clusters and their membership (N = 349). Cluster-specific outcomes were assessed after a median follow-up of 3 years. A classifier was programmed to determine cluster stability and was validated in an independent cohort of new patients recruited to the registry (n = 245). Five clusters were identified. Cluster 1 (34%) were atopic with early onset disease, cluster 2 (21%) were obese with late onset disease, cluster 3 (15%) had the least severe disease, cluster 4 (15%) were the eosinophilic with late onset disease and cluster 5 (15%) had significant fixed airflow obstruction. At follow-up, the proportion of subjects treated with oral corticosteroids increased in all groups with an increase in body mass index. Exacerbation frequency decreased significantly in clusters 1, 2 and 4 and was associated with a significant fall in the peripheral blood eosinophil count in clusters 2 and 4. Stability of cluster membership at follow-up was 52% for the whole group with stability being best in cluster 2 (71%) and worst in cluster 4 (25%). In an independent validation cohort, the classifier identified the same 5 clusters with similar patient distribution and characteristics. Statistical cluster analysis can identify distinct phenotypes with specific outcomes. Cluster membership can be determined using a classifier, but when treatment is optimised, cluster stability is poor.

  20. Seizure frequency and severity: How really important are they for the quality of life of patients with refractory epilepsy

    PubMed Central

    Viteva, Ekaterina Ivanova

    2014-01-01

    Introduction: The data in the scientific literature about the significance of seizure severity and frequency for the quality of life (QOL) of patients with refractory epilepsy (RE) are contradictory. Objective: Our objective was to assess the impact of the seizure severity and frequency on the QOL of Bulgarian patients with RE. Materials and Methods: A total of 70 patients with RE were studied by examining the medical documentation and seizure diaries. All study participants completed quality of life epilepsy inventory (QOLIE-89). Seizure severity of only 59 patients who had a seizure in the last month was assessed by the Liverpool seizure severity scale. Results: A limited negative impact of the seizure severity and frequency on some aspects of the physical health, epilepsy, all aspects of the social health and epilepsy and the overall QOL has been demonstrated. A weak to moderate reverse correlation between the specified factors and the respective QOLIE-89 subscales has been found. Conclusion: The clinical factors seizure severity and seizure frequency have a limited negative impact mostly on the social aspects of QOL. The study results support the multidisciplinary approach to persons with epilepsy. PMID:24753657

  1. Predictors of hospital and one-year mortality in intensive care patients with refractory status epilepticus: a population-based study.

    PubMed

    Kantanen, Anne-Mari; Kälviäinen, Reetta; Parviainen, Ilkka; Ala-Peijari, Marika; Bäcklund, Tom; Koskenkari, Juha; Laitio, Ruut; Reinikainen, Matti

    2017-03-23

    The aim was to determine predictors of hospital and 1-year mortality in patients with intensive care unit (ICU)-treated refractory status epilepticus (RSE) in a population-based study. This was a retrospective study of the Finnish Intensive Care Consortium (FICC) database of adult patients (16 years of age or older) with ICU-treated RSE in Finland during a 3-year period (2010-2012). The database consists of admissions to all 20 Finnish hospitals treating RSE in the ICU. All five university hospitals and 11 out of 15 central hospitals participated in the present study. The total adult referral population in the study hospitals was 3.92 million, representing 91% of the adult population of Finland. Patients whose condition had a post-anoxic aetiological basis were excluded. We identified 395 patients with ICU-treated RSE, corresponding to an annual incidence of 3.4/100,000 (95% confidence interval (CI) 3.04-3.71). Hospital mortality was 7.4% (95% CI 0-16.9%), and 1-year mortality was 25.4% (95% CI 21.2-29.8%). Mortality at hospital discharge was associated with severity of organ dysfunction. Mortality at 1 year was associated with older age (adjusted odds ratio (aOR) 1.033, 95% CI 1.104-1.051, p = 0.001), sequential organ failure assessment (SOFA) score (aOR 1.156, CI 1.051-1.271, p = 0.003), super-refractory status epilepticus (SRSE) (aOR 2.215, 95% CI 1.20-3.84, p = 0.010) and dependence in activities of daily living (ADL) (aOR 2.553, 95% CI 1.537-4.243, p < 0.0001). Despite low hospital mortality, 25% of ICU-treated RSE patients die within a year. Super-refractoriness, dependence in ADL functions, severity of organ dysfunction at ICU admission and older age predict long-term mortality. Retrospective registry study; no interventions on human participants.

  2. Phenolic Resin for Refractories

    NASA Astrophysics Data System (ADS)

    Irie, Shunsuke; Rappolt, James

    Refractories are used in furnaces and boilers that process steel, cement, or glass as well as incinerators that operate at high temperatures. A variety of binders is used when refractories are manufactured. In this chapter, the use of phenolic resin as a binder for refractories is described. There are several factors that support the use of phenolic resins in comparison to other refractory binders. These include the following: 1. Both adhesion and green body strength are high.

  3. 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.

  4. Outcome of myeloablative allogeneic peripheral blood hematopoietic stem cell transplantation for refractory/relapsed AML patients in NR status.

    PubMed

    Liu, Na; Ning, Hong-Mei; Hu, Liang-Ding; Jiang, Min; Xu, Chen; Hu, Jiang-Wei; Wang, Jun; Li, Yu-Hang; Li, Bo-Tao; Lou, Xiao; Yang, Fan; Chen, Jian-Lin; Su, Yong-Feng; Li, Meng; Wang, Hong-Ye; Ren, Jing; Feng, Yue-Qian; Zhang, Bin; Wang, Dan-Hong; Chen, Hu

    2015-12-01

    To further find effective method to improve the long term survival of refractory or relapsed acute myeloid leukemia (AML) patients, we retrospectively analyzed the outcomes of myeloablative hematopoietic stem cell transplantation (HSCT) for 133 consecutive patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) therapy related AML(t-AML) in not remission status. The overall 3-year OS and DFS were 40.9% and 35.6% respectively. The variables associated with improved long term DFS were a bone marrow blast cell count less than 20% and an intensified conditioning regimen. In addition, the t-AML group had higher rates of relapse and III-IV acute GVHD than the primary AML group. The unrelated donor group had similar OS and DFS with sibling groups. Our study suggested that decreasing bone marrow blast cell counts before HSCT and strengthening the conditioning regimen may improve long-term DFS for refractory/relapsed AML patients, and unrelated donor group can get similar effect when compared to the sibling group.

  5. The mechanism of action of vagus nerve stimulation for refractory epilepsy: the current status.

    PubMed

    Vonck, K; Van Laere, K; Dedeurwaerdere, S; Caemaert, J; De Reuck, J; Boon, P

    2001-09-01

    Vagus nerve stimulation (VNS) is a neurophysiologic treatment for patients with medically or surgically refractory epilepsy. Since the first human implant in 1989, more than 10,000 patients have been treated with VNS. The precise mechanism of action remains to be elucidated. Animal experiments with VNS were initially performed to demonstrate efficacy and safety preceding the clinical trials in human patients. Mechanism of action research involving animal experiments can provide essential clues. Animal experiments are often labor-intensive even in the hands of experienced researchers, however, and the results remain only a reflection of the complicated pathophysiologic systems of the human brain. Mechanism of action research in human patients treated with VNS is particularly challenging because of safety concerns, the large number of patients required, and the heterogeneous nature of various small patient series. This study provides an overview of the progress that has been made in the past 10 years through neurophysiologic, neuroanatomic, neurochemical, and cerebral blood flow studies in animals and patients treated with VNS. Further elucidation of the mechanism of action of VNS may increase its clinical efficacy. It may also provide inspiration for the development of new therapeutic modalities for refractory epilepsy.

  6. Differential Diagnosis of Genetic Disorders Associated with Moderate to Severe Refractory Eczema and Elevated Immunoglobulin E.

    PubMed

    Arjona Aguilera, C; Albarrán Planelles, C; Tercedor Sánchez, J

    2016-03-01

    The association of moderate to severe eczema and elevated plasma levels of immunoglobulin E is a characteristic not only of atopic dermatitis but also of various genodermatoses: hyperimmunoglobulin E syndromes, Omenn syndrome, Netherton syndrome, peeling skin syndrome type B, severe dermatitis, multiple allergies, and metabolic wasting syndrome, Wiskott-Aldrich syndrome, prolidase deficiency, Loeys-Dietz syndrome, IPEX syndrome, STAT5B deficiency, and pentasomy X. The clinical presentation of these genodermatoses -typically in children- is consistent with severe atopic dermatitis. Immunoglobulin E is elevated from birth and response to conventional treatments is poor. Diagnosis is further complicated by the fact that these genodermatoses often share other clinical manifestations and laboratory findings. We present practical guidelines for differentiating among these various entities, with the aim of helping physicians decide what type of genetic test should be carried out -and when- in order to establish a definitive diagnosis.

  7. Severe Acute Pulmonary Toxicity Associated with Brentuximab in a Patient with Refractory Hodgkin's Lymphoma

    PubMed Central

    Sabet, Yasmin; Ramirez, Saul; Rosell Cespedes, Elizabeth; Rensoli Velasquez, Marimer; Porres-Muñoz, Mateo; Gaur, Sumit; Figueroa-Casas, Juan B.; Porres-Aguilar, Mateo

    2016-01-01

    Acute pulmonary toxicity associated with brentuximab appears to be a rare but serious adverse effect that can be potentially fatal. We report the case of a twenty-nine-year-old female with Hodgkin's lymphoma who was treated with brentuximab and later presented with severe acute pulmonary toxicity; she improved after the discontinuation of brentuximab and administration of antibiotics and glucocorticoid therapy. Currently there is very little data in the literature in regard to the clinical manifestations and characteristics of patients taking brentuximab and the potential development of acute severe pulmonary toxicity, as well as the appropriate therapeutic approach, making this particular case of successful treatment and resolution unique. PMID:27190667

  8. A complex transcatheter mitral valve replacement and repair for the treatmemt of refractory severe mitral regurgitation.

    PubMed

    Condado, Jose F; Babaliaros, Vasilis C; Thourani, Vinod H; Jensen, Hanna K; Kim, Dennis W; Kaebnick, Brian W; Block, Peter C; Lerakis, Stamatios

    2017-01-23

    Hybrid transcatheter Mitral Valve-in-Ring and Mitral Valve-in-Valve procedures can be an alternative to traditional surgical valve replacement in patients with high surgical risk. We present a case of a 65-year-old male with recurrent severe mitral regurgitation (MR) that failed two traditional surgical attempts due to severe chest fibrosis. We performed a mitral valve-in ring replacement with a Sapien valve followed by a mitral valve-in-valve replacement with a Melody valve. Patient had a residual paravalvular leak that was closed with a vascular plug. Our case proves that is feasible to treat selected patients with MR using a hybrid transcatheter approach.

  9. High-frequency oscillatory ventilation is an effective treatment for severe pediatric acute respiratory distress syndrome with refractory hypoxemia

    PubMed Central

    Guo, Yu-Xiong; Wang, Zhao-Ni; Li, Ya-Ting; Pan, Li; Yang, Li-Fen; Hu, Yan; Sun, Yue-Yu; Cai, Liang-Ming; Chen, Zhuang-Gui

    2016-01-01

    Background and purpose Early or primary application of high-frequency oscillatory ventilation (HFOV) has been recently suggested not to offer benefit to patients with acute respiratory distress syndrome (ARDS). However, the rescue effects of HFOV on severe pediatric acute respiratory distress syndrome (PARDS) with hypoxemia refractory to conventional mechanical ventilation (CMV) remain unclear. This study aimed to determine whether severe PARDS children would benefit from HFOV when oxygenation deteriorated on CMV and to identify any potential risk factors related to mortality. Patients and methods In a retrospective and observational study, 48 children with severe PARDS between January 2009 and July 2015 were divided into two groups: 26 in HFOV group and 22 in CMV group. Data regarding demographic, underlying conditions, arterial blood gases and clinical outcomes were collected and analyzed. Results The arterial partial pressure of oxygen (PaO2)/fraction of inspiration oxygen (FiO2) ratio and PaO2 improved significantly during HFOV, whereas arterial partial pressure of carbon dioxide (PaCO2) and oxygenation index decreased. There was no statistical difference in the in-hospital mortality between the groups (P=0.367). The odds ratio of survival in HFOV group was 2.74 (95% confidence interval 0.52 to 14.58, P=0.237). The pediatric intensive care unit length of stay and total ventilation duration were longer in HFOV group (P=0.048 and P=0.000, respectively). Vasoactive agents were used more frequently in HFOV group (P=0.007). The incidence of new air leak was similar between the two groups (P=0.674). The presence of multiple organ dysfunction syndrome and heavier body weight were identified as predictors of mortality in the HFOV group (P=0.006 and P=0.020, respectively). Conclusion HFOV as an efficient alternative therapy could significantly improve hypoxemia and promote CO2 removal in severe PARDS children when oxygenation progressively worsens on CMV. PMID:27799777

  10. Current Status of Autologous Stem Cell Transplantation in Relapsed and Refractory Hodgkin's Lymphoma

    PubMed Central

    Colpo, Anna; Hochberg, Ephraim

    2012-01-01

    Despite the relatively high long-term disease-free survival (DFS) rate for patients with Hodgkin lymphoma (HL) with modern combination chemotherapy or combined modality regimens, ∼20% of patients die from progressive or relapsed disease. The standard treatment for relapsed and primary refractory HL is salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT), which has shown a 5-year progression-free survival rate of ∼50%–60%. Recent developments in a number of diagnostic and therapeutic modalities have begun to improve these results. Functional imaging, refinement of clinical prognostic factors, and development of novel biomarkers have improved the predictive algorithms, allowing better patient selection and timing for ASCT. In addition, these algorithms have begun to identify a group of patients who are candidates for more aggressive treatment beyond standard ASCT. Novel salvage regimens may potentially improve the rate of complete remission prior to ASCT, and the use of maintenance therapy after ASCT has become a subject of current investigation. We present a summary of developments in each of these areas. PMID:22210089

  11. Therapeutic Efficacy of Fresh, Allogeneic Mesenchymal Stem Cells for Severe Refractory Feline Chronic Gingivostomatitis.

    PubMed

    Arzi, Boaz; Clark, Kaitlin C; Sundaram, Ayswarya; Spriet, Mathieu; Verstraete, Frank J M; Walker, Naomi J; Loscar, Megan R; Fazel, Nasim; Murphy, William J; Vapniarsky, Natalia; Borjesson, Dori L

    2017-08-01

    Mesenchymal stem cells (MSCs) have potent immunomodulatory functions and are a promising therapy for immune-mediated inflammatory disorders. We previously demonstrated the efficacy of fresh, autologous, adipose-derived MSCs (ASCs) to treat feline chronic gingivostomatitis (FCGS), a chronic oral mucosal inflammatory disease similar to human oral lichen planus. Here, we investigate the use of fresh allogeneic ASCs for treatment of FCGS in seven cats. Radiolabeled ASCs were also tracked systemically. Each cat received two intravenous injections of 20 million ASCs, 1 month apart. Oral inflammation, blood lymphocyte subsets, anti-fetal bovine serum antibody levels, ASC crossmatching and serum proteins and cytokine concentrations were determined. Four of the 7 cats (57%) responded to treatment [complete clinical remission (n = 2) or substantial clinical improvement (n = 2)]. Three cats were nonresponders. Prior to therapy, most cats had increased circulating CD8+ T cells, decreased CD8(lo) cells, and a decreased CD4/CD8 ratio, however clinical resolution was not associated with normalization of these parameters. Nonresponders showed more severe systemic inflammation (neutrophilia, hyperglobulinemia and increased interferon gamma and tumor necrosis factor alpha concentration) prior to ASC therapy. Clinical remission took up to 20 months and no clinical relapse has occurred. A higher fraction of radiolabeled ASCs were identified in the oral cavity of FCGS affected cats than the control cat. The administration of fresh, allogenic ASCs appeared to have lower clinical efficacy with a delayed response as compared to the fresh, autologous ASCs. In addition, the mechanism(s) of action for autologous and allogenic ASCs may differ in this model of oral inflammation. Stem Cells Translational Medicine 2017;6:1710-1722. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  12. Ten-year followup of infliximab therapy in rheumatoid arthritis patients with severe, longstanding refractory disease: a cohort study.

    PubMed

    De Keyser, Filip; De Kock, Joris; Leroi, Hermine; Durez, Patrick; Westhovens, René

    2014-07-01

    Our study describes the 10-year followup data of the Belgian Expanded Access Program (EAP) for infliximab (IFX), which included patients with active rheumatoid arthritis who were refractory to methotrexate. The objectives of the study were to evaluate the continuation rate, reasons for discontinuation, and longterm disease control under IFX treatment, and to study baseline characteristics associated with longterm successful IFX therapy. Between February 2000 and September 2001, 511 patients were enrolled in the Belgian IFX EAP, and 507 effectively started IFX therapy. Previously reported data showed that 160 patients were still treated with IFX after 7 years of followup. We describe the therapy status, reasons for IFX discontinuation, and the level of disease activity of this subgroup after 10 years of followup. Baseline characteristics of the total EAP cohort were used to describe variables associated with longterm successful IFX treatment. After 10 years of followup, 110 of the 507 patients (21.7%) were still receiving IFX treatment. In the 7-year to 10-year period, which is the focus of the current study, 16 patients were lost to followup and 34 patients discontinued IFX treatment, mainly because of loss of efficacy. Patients successfully treated with IFX for 10 years had lower baseline values for 28-joint Disease Activity Score (DAS28), patient pain scale, physician visual analog scale, and Health Assessment Questionnaire in comparison with the rest of the study cohort. The mean DAS28 level of the subgroup still taking IFX after 10 years was 2.55 ± 1.01. In the Belgian EAP, 21.7% of patients continued to receive maintenance IFX treatment after 10 years of followup. IFX provided good longterm disease control in these patients.

  13. Dorsal anterior cingulotomy and anterior capsulotomy for severe, refractory obsessive-compulsive disorder: a systematic review of observational studies.

    PubMed

    Brown, Lauren T; Mikell, Charles B; Youngerman, Brett E; Zhang, Yuan; McKhann, Guy M; Sheth, Sameer A

    2016-01-01

    OBJECT The object of this study was to perform a systematic review, according to Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA) and Agency for Healthcare Research and Quality (AHRQ) guidelines, of the clinical efficacy and adverse effect profile of dorsal anterior cingulotomy compared with anterior capsulotomy for the treatment of severe, refractory obsessive-compulsive disorder (OCD). METHODS The authors included studies comparing objective clinical measures before and after cingulotomy or capsulotomy (surgical and radiosurgical) in patients with OCD. Only papers reporting the most current follow-up data for each group of investigators were included. Studies reporting results on patients undergoing one or more procedures other than cingulotomy or capsulotomy were excluded. Case reports and studies with a mean follow-up shorter than 12 months were excluded. Clinical response was defined in terms of a change in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score. The authors searched MEDLINE, PubMed, PsycINFO, Scopus, and Web of Knowledge through October 2013. English and non-English articles and abstracts were reviewed. RESULTS Ten studies involving 193 participants evaluated the length of follow-up, change in the Y-BOCS score, and postoperative adverse events (AEs) after cingulotomy (n = 2 studies, n = 81 participants) or capsulotomy (n = 8 studies, n = 112 participants). The average time to the last follow-up was 47 months for cingulotomy and 60 months for capsulotomy. The mean reduction in the Y-BOCS score at 12 months' follow-up was 37% for cingulotomy and 55% for capsulotomy. At the last follow-up, the mean reduction in Y-BOCS score was 37% for cingulotomy and 57% for capsulotomy. The average full response rate to cingulotomy at the last follow-up was 41% (range 38%-47%, n = 2 studies, n = 51 participants), and to capsulotomy was 54% (range 37%-80%, n = 5 studies, n = 50 participants). The rate of transient AEs was 14.3% across

  14. Simultaneous penile lengthening and penile prosthesis implantation in patients with Peyronie's disease, refractory erectile dysfunction, and severe penile shortening.

    PubMed

    Sansalone, Salvatore; Garaffa, Giulio; Djinovic, Rados; Egydio, Paulo; Vespasiani, Giuseppe; Miano, Roberto; Loreto, Carla; Ralph, David J

    2012-01-01

    Due to loss of length, patients who had penile prosthesis implantation for Peyronie's disease (PD) show a statistically significant reduction in their levels of satisfaction when compared with the general implant population. The aim of this study is to report our experience of penile lengthening with circumferential graft during penile prosthesis implantation in patients with PD and severe penile shortening. Between March 2006 and February 2008, 23 patients with PD, refractory erectile dysfunction, and severe penile shortening underwent penile lengthening with circumferential graft and concomitant implantation of an inflatable penile prosthesis. Surgical outcome and complications have been recorded during postoperative follow-up. Patients' satisfaction has been assessed 6 months postoperatively with the administration of the modified Erectile Dysfunction Index of Treatment Satisfaction (EDITS) questionnaire. After an average follow-up of 22 months (range 6-36), 20 patients attended all the postoperative follow-up visits and returned the EDITS questionnaire. An average length gain of 2.8 cm (range 2.2-4.5) was recorded, and all patients were able to cycle the device and engage in penetrative sexual intercourse. Patient recorded complications included diminished glans sensitivity in four (20%) and persistent dorsal curvature of less than 15° in three (15%). Overall, 18 patients (90%) were satisfied with the cosmetic and functional result of surgery. Penile lengthening with circumferential graft during penile prosthesis implantation in patients with PD represents a safe and reproducible technique that yields higher satisfaction rates than penile prosthesis implantation alone in patients with severe penile shortening. © 2011 International Society for Sexual Medicine.

  15. Mortality and recovery from refractory status epilepticus in the intensive care unit: a 7-year observational study.

    PubMed

    Sutter, Raoul; Marsch, Stephan; Fuhr, Peter; Rüegg, Stephan

    2013-03-01

    Refractory status epilepticus (RSE) is a life-threatening neurologic emergency with high mortality and morbidity. The aim of this study was to identify and quantify associations between clinical characteristics of adult RSE patients and outcome. Comprehensive medical chart review was performed of all consecutive adult RSE patients treated on the intensive care units of an academic tertiary care center between 2005 and 2011. Demographics, RSE etiologies and duration, comorbidities, as well as outcomes were assessed. Associations between clinical characteristics and death were quantified. Of 260 patients with status epilepticus, 111 developed RSE. Hypoxic encephalopathy (23%), brain tumors (14%), known and uncontrolled epilepsy (10%), and ischemic stroke (8%) were the main etiologies. During hospitalization 38% of patients died. Hypoxic encephalopathy (HE) and brain tumors were independently associated with death (relative risk [RR] 2.41, 95% confidence interval [CI] 1.40-4.12; p = 0.001 and RR 2.81, 95%CI 1.59-4.96; p < 0.0001). The estimated hazard ratio of death was 3.1 (95% CI1.6-6.0; p = 0.001) for patients with HE and 1.1 (95% CI 0.5-2.3; p = 0.745) for patients with brain tumors. RSE duration and nonconvulsive status epilepticus in coma were independently associated with death (for every hour RR 1.001; 95%CI 1.00-1.002; p = 0.011 and RR 3.62; 95%CI 1.34-9.77; p = 0.005). Brain tumors and HE had high relative risks for death and were independently associated with mortality in our cohort of critically ill RSE patients. Other clinical characteristics, as well as the use of intravenous anesthetic drugs and mechanical ventilation, may not be strongly related to outcome and should therefore be used cautiously for informed decision making regarding treatment. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  16. Use of Longitudinal Dose-Response Modeling to Support the Efficacy and Tolerability of Alitretinoin in Severe Refractory Chronic Hand Eczema (CHE).

    PubMed

    Schmith, G D; Singh, R; Gomeni, R; Graff, O; Hamedani, A G; Troughton, J S; Learned, S M

    2015-04-01

    Longitudinal dose-response analyses of alitretinoin (an investigational agent in the US) were conducted to supplement results from phase III studies in severe, refractory chronic hand eczema, with objectives to address several outstanding development issues (e.g., optimal dose, possible factors affecting efficacy and/or tolerability). Models were fitted to the physicians' global assessment score and triglycerides over time. Five hundred trials were simulated to evaluate the relevance of findings. Analyses clarified that the optimal dose of alitretinoin was 30 mg once daily, where response rates were ∼10% over placebo at 12 weeks and increased by 5-7% over placebo for every 4 weeks thereafter, for up to 24 weeks. Elderly subjects had higher magnitudes of efficacy and an increased probability of high triglycerides. Results from analyses sufficiently addressed the development issues, thereby adding to the weight of evidence supporting the efficacy and safety of alitretinoin in the treatment of severe, refractory chronic hand eczema.

  17. [Induced hypothermia/normothermia with general anesthesia prevents neurological damage in children with febrile refractory status epilepticus].

    PubMed

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

    2011-11-01

    Refractory status epilepticus (RSE) is defined as persistence of seizure activity despite appropriate medical and antiepileptic drug (AED) therapy. Febrile RSE is often caused by presumed encephalitis and has a high morbidity rate. In addition, it is believed that hyperthermia aggravates epileptic brain damage. The efficacy of hypothermia/normothermia (H/N) therapy against brain damage has been proposed, but there have been limited studies reporting on the efficacy of this treatment against febrile RSE. To study the efficacy of induced H/N with general anesthesia therapy in children with febrile RSE, a retrospective review of RSE cases was conducted in 28 children hospitalized in the tertiary pediatric intensive care center of Kobe Children's Hospital, Japan, between October 2002 and August 2009. Clinical outcomes and neurological sequelae using the Pediatric Cerebral Performance Category Scale (PCPC) score were compared after one month of treatment with either H/N (34 degrees C-36 degrees C) with general anesthesia therapy or with other conventional therapies. Cases were categorized as those with good recovery (PCPC=1) or poor outcome (PCPC=2-6). Twelve children underwent H/N with general anesthesia therapy, while 16 children were treated by conventional therapy using intravenous diazepam and/or midazolam. Treatment with H/N significantly improved outcome compared to conventional therapies (p=0.024; Fisher's exact test). Five of 6 patients with poor outcome had a final diagnosis of acute encephalopathy with febrile convulsive status epilepticus (AEFCSE). Treatment with H/N therapy may reduce neurological damage in the development of AEFCSE caused by febrile RSE in children.

  18. IVIG - A cure to severe refractory NAP-1 Clostridium difficile colitis? A case of successful treatment of severe infection, which failed standard therapy including fecal microbiota transplants and fidaxomicin.

    PubMed

    Coffman, Kelley; Chen, Xian Jie Cindy; Okamura, Charles; Louie, Eddie

    2017-01-01

    The mainstay treatment of Clostridium difficile infections (CDI) is antimicrobials with growing support for fecal microbiota transplants. We report the first case of an elderly man with severe refractory NAP-1 pseudomembranous CDI who failed all medical therapy and two fecal transplants with response only seen after administration of intravenous immunoglobulin.

  19. Nutritional status, adiposity and asthma severity and control in children.

    PubMed

    Silveira, Denise Halpern; Zhang, Linjie; Prietsch, Silvio O M; Vecchi, Amilcare Angelo; Susin, Lulie Rosane Odeh

    2015-10-01

    To investigate association between nutritional status, adiposity and asthma severity and control in children. We conducted a case control study at two teaching hospitals in Brazil. Cases were children (3-12 years) with persistent asthma and age-matched controls were those with intermittent asthma. Nutritional status was assessed by body mass index (BMI). Adiposity was assessed by sum of skinfolds and waist circumference (WC). Crude and adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using conditional logistic regression or multinomial logistic regression as appropriate. Two hundred sixty-eight cases and 126 controls were included. Obesity (>2 BMI z-score for age) was significantly associated with persistent asthma (adjusted OR 2.62; 95% CI 1.39-4.95). There was a significant linear relationship between BMI z-scores (≤1, >1 to ≤2, >2) and risk of having persistent asthma (P = 0.003 for linear trend). Children with WC >90th percentile had a higher risk of persistent asthma when compared with those with WC ≤90th percentile (adjusted OR 3.38; 95% CI 1.26-9.06). No significant difference was found in terms of nutritional status and adiposity between children whose asthma was controlled by inhaled corticosteroids and those requiring inhaled corticosteroids plus other medications for asthma control. Obesity measured by BMI and increased abdominal adiposity are significantly associated with risk of persistent asthma but not type of controller medications. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  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. 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 Central

    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

    2016-01-01

    had stiff-person syndrome (one with seizures 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). Interpretation 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. Funding 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. PMID:24462240

  2. Brentuximab vedotin administered to platinum-refractory, transplant-naïve Hodgkin lymphoma patients can increase the proportion achieving FDG PET negative status.

    PubMed

    Onishi, Maika; Graf, Solomon A; Holmberg, Leona; Behnia, Sanaz; Shustov, Andrei R; Schiavo, Karen; Philip, Mary; Libby, Edward N; Cassaday, Ryan D; Pagel, John M; Roden, Jennifer E; Maloney, David G; Green, Damian J; Till, Brian G; Press, Oliver W; Smith, Stephen D; Gopal, Ajay K

    2015-12-01

    Normalization of fluorodeoxyglucose positron emission tomography (FDG PET) imaging prior to high-dose therapy and autologous stem cell transplantation (ASCT) improves outcomes in relapsed and refractory (RR) Hodgkin lymphoma (HL), but many patients refractory to platinum-based salvage regimens are unable to achieve this goal. We therefore investigated whether brentuximab vedotin (BV) could normalize FDG PET in platinum-refractory HL prior to ASCT. Fifteen consecutive patients with RR HL and FDG PET positive disease after platinum-based salvage therapy were treated with a median of 4 cycles of BV. Normalization of FDG PET (Deauville ≤2) occurred in 8/15 (53%) patients but was only observed in patients that had achieved partial remission or stable disease after platinum-based salvage therapy. All patients eventually proceeded to ASCT, regardless of FDG PET status. Our data suggest that BV can normalize FDG PET in a subset of patients with platinum-refractory HL prior to ASCT. Copyright © 2014 John Wiley & Sons, Ltd.

  3. 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.

  4. Stiripentol is anticonvulsant by potentiating GABAergic transmission in a model of benzodiazepine-refractory status epilepticus.

    PubMed

    Grosenbaugh, Denise K; Mott, David D

    2013-04-01

    Benzodiazepines (BZDs) are first-line therapy for treatment of status epilepticus (SE). However, BZD treatment is negatively affected by seizure duration due to decreases in BZD-sensitive GABA(A) receptors during prolonged SE. Stiripentol (STP) is an anticonvulsant that is used as add-on treatment for Dravet Syndrome. Recent studies have shown that STP is a positive allosteric modulator of the GABA(A) receptor. The subunit selectivity of STP at this receptor suggests that it would be anticonvulsant in both brief as well as prolonged SE. We tested this possibility by comparing the ability of STP and diazepam (DZP), a commonly used BZD, to terminate behavioral convulsions in a rodent model of pharmacoresistant SE. We found that STP was anticonvulsant in this model and remained effective during prolonged SE, unlike DZP which exhibited a 14 fold increase in its ED(50). Whole cell recording from hippocampal slices from these animals revealed that STP potentiated GABAergic IPSCs, as well as tonic GABAergic current by acting at a site on the GABA(A) receptor separate from the BDZ binding site. Potentiation of GABAergic currents by STP remained intact during prolonged SE, while potentiation by DZP was lost. Both IPSC potentiation and anticonvulsant activity of STP were greater in younger animals than in adults. These findings suggest that at doses that yield therapeutically relevant concentrations, STP is anticonvulsant by potentiating GABAergic inhibition and that the subunit selectivity profile of STP enables it to remain effective despite GABA(A) receptor subunit changes during prolonged SE. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Severe cefepime-induced status epilepticus treated with haemofiltration.

    PubMed

    Suarez-de-la-Rica, A; Hernández-Gancedo, C; López-Tofiño, A; Maseda, E; Gilsanz, F

    2016-01-01

    Neurotoxicity caused by cefepime may occur predominantly in patients with impaired renal function. A case of a cefepime-induced non-convulsive status epilepticus (NCSE) is presented. A 65-year-old woman suffered a severe NCSE due to cefepime in the presence of acute renal failure, requiring coma induction with sodium thiopental. A serious interaction between valproic acid (VPA) and meropenem was also produced after changing cefepime to meropenem. Continuous veno-venous haemofiltration was employed to improve cefepime clearance, and the patient progressively regained her previous mental condition. In conclusion, the cefepime dose must be adjusted according to renal function in order to avoid toxicity in patients with renal failure. Electroencephalogram should be considered in cases of acute confusional state in patients receiving cefepime, to achieve early detection of NCSE. Continuous renal replacement therapy may be successfully employed in severe cases in order to accelerate cefepime removal. Likewise, meropenem should not be used concomitantly with VPA. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. [Refractory anemias].

    PubMed

    Efira, A; Azerad, M-A

    2013-09-01

    Refractory anemia, also known as myelodysplastic syndromes, forms a group of clonal diseases characterized by cytopenias with mostly rich bone marrow. Preferentially reaching an older population, the prognosis depends on both comorbidities and characteristics of the disease, which have been grouped into a score established in 1997 ("IPSS = International Prognostic Scoring System") and revised in 2012 ("R-IPSS = Revised IPSS"). Overall survival and risk of transformation into acute nonlymphoblastic leukemia can now be estimated fairly accurately. Based on these characteristics, the treatment will be mainly supportive or will use several new molecules: growth factors, lenalidomide, 5-azacitidine, etc. A minority of patients may also benefit from allogeneic BMT or sometimes immunosuppressive therapy.

  7. Midazolam and thiopental for the treatment of refractory status epilepticus: a retrospective comparison of efficacy and safety.

    PubMed

    Bellante, Flavio; Legros, Benjamin; Depondt, Chantal; Créteur, Jacques; Taccone, Fabio Silvio; Gaspard, Nicolas

    2016-04-01

    Current management guidelines for refractory status epilepticus (RSE) recommend the use of intravenous continuous anesthetic therapy, but there is little evidence to guide the selection of the most efficacious and safest drug. We conducted a retrospective study to evaluate the efficacy and safety of midazolam versus thiopental for treatment of RSE. Retrospective case-control series of prospectively identified patients treated with midazolam or thiopental for RSE between January 2007 and December 2014. The primary outcome was control of RSE. Secondary outcomes included the rate of adverse events, intensive care unit (ICU) and hospital length of stay, hospital mortality and long-term neurological outcome, assessed with the extended Glasgow outcome scale (GOS-E) at discharge and at six 6 months. A total of 33 patients were included, 19 treated with midazolam and 14 with thiopental. Groups were similar for demographic data, clinical variables, comorbidity and the underlying cause of RSE. The rate of control of SE did not differ between groups (63 vs. 64 %). Adverse events including hypotension (mean arterial pressure <70 mmHg) requiring vasopressors, infections, anemia requiring red blood cells transfusion, leucopenia (<4000/mm(3)), and hyponatremia (<130 mEq/l) were more frequent during thiopental infusion. Furthermore, patients treated with midazolam had a shorter median ICU length of stay (6 vs. 15 days; p = 0.02) and better GOS-E at 6 months (8 [8] vs. 4 [4, 5]; p = 0.01). These findings suggest that continuous midazolam administration is as efficacious as thiopental infusion for the treatment of RSE; however, midazolam was associated with a significantly lower number of adverse events. These findings should be confirmed in larger multicenter trials.

  8. Isoflurane Use in the Treatment of Super-Refractory Status Epilepticus is Associated with Hippocampal Changes on MRI.

    PubMed

    Ikeda, Kristin M; Connors, Robert; Lee, Donald H; Khandji, Alexander G; Claassen, Jan; Young, G Bryan

    2017-06-01

    Refractory status epilepticus (RSE) is associated with high morbidity and mortality. Experts recommend aggressive management with continuous intravenous infusions or inhaled anesthetics such as isoflurane. However, there is concern that MRI changes in RSE reflect isoflurane neurotoxicity. We performed a case-control study to determine whether isoflurane is neurotoxic, based on MRI signal changes. We performed a retrospective case-control study of the incidence of MRI changes in RSE treated with and without isoflurane. Charts were reviewed for demographic and treatment information. T1, T2, and FLAIR sequences of MRIs were reviewed independently by two neuroradiologists blinded to treatment group for presence or absence of signal change or atrophy in the meninges, cortex, white matter, basal ganglia, thalamus, hippocampus, brainstem, and cerebellum. Eight cases of RSE receiving treatment with isoflurane were identified and double-matched with 15 controls who received only intravenous anesthetics. Baseline characteristics were similar. Hippocampal signal change was observed more frequently in cases receiving isoflurane (p = 0.026). Hippocampal signal changes were associated with isoflurane use in patients with RSE. They were also associated with number of seizure days prior to MRI and the use of multiple anesthetic agents. Similar changes have been seen as a result of RSE itself, and one cannot rule out the possibility these changes represent seizure-related effects. If isoflurane-related, these hippocampal signal changes may be the result of a direct neurotoxic effect of prolonged isoflurane use or failure of isoflurane to protect the hippocampus from seizure-induced injury despite achieving electrographic burst-suppression.

  9. Salvage treatment with temozolomide in refractory or relapsed primary central nervous system lymphoma and assessment of the MGMT status.

    PubMed

    Makino, Keishi; Nakamura, Hideo; Hide, Taku-Ichiro; Kuratsu, Jun-Ichi

    2012-01-01

    High-dose methotrexate (HD-MTX) is effective in the initial treatment of primary central nervous system lymphoma (PCNSL). Because treatment options in patients with progressive or recurrent PCNSL are limited, prognosis is poor. Temozolomide, a well-tolerated oral alkylating agent that permeates the blood brain barrier (BBB), is effective against malignant glioma and recurrent PCNSL. The gene for the deoxyribonucleic acid (DNA) repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT), which is closely related to cellular sensitivity to alkylating agents, is inactivated by promoter hypermethylation. We evaluated the results of temozolomide treatment and the methylation status of the promoter region of the MGMT gene in 17 patients (median age 68 years) with refractory or relapsed PCNSL. They were immunocompetent and had received initial treatment with HD-MTX (3.5 g/m(2)) with or without irradiation. All were treated with temozolomide 150-200 mg/m(2), for 5 days in the course of 28 days; treatment was continued until disease progression. We observed five complete remissions, five partial responses (PRs) with stable disease (SD), and seven with disease progression. Median overall survival after the temozolomide treatment was 6.7 months. One patient manifested grade 3 neutropenia and thrombocytopenia. Eleven tumor specimens were available for MGMT analysis. MGMT promoter methylation (mMGMT) in the tumor tissue was found in 4 (36.4%), the other seven harbored a non-methylated MGMT promoter (nmMGMT). There was no statistically significant difference in median overall survival between patients with mMGMT (11.1 months) and nmMGMT (6.7 months) (P = 0.63). Although some patients were elderly and had been heavily pre-treated, temozolomide resulted in a complete response (CR) in 29% and was well tolerated without any major toxicity.

  10. A Practical Approach to Ketogenic Diet in the Pediatric Intensive Care Unit for Super-Refractory Status Epilepticus.

    PubMed

    Farias-Moeller, Raquel; Bartolini, Luca; Pasupuleti, Archana; Brittany Cines, R D; Kao, Amy; Carpenter, Jessica L

    2017-04-01

    Super-refractory status epilepticus (SRSE) ensues when there is no improvement of seizure control in response to anesthetic therapy or seizure recurrence after reduction of anesthetic agents. There is no consensus on standard of care for SRSE. Ketogenic diet (KD) has reported success, but technical challenges exist including inability to feed patients, concomitant steroid use, acidotic states, and lack of dieticians with experience. The optimal protocol for KD is yet to be determined. We describe our approach to initiation of KD in the pediatric intensive care unit (PICU). Patients with SRSE who had KD initiation in the PICU were identified. Data from the hospital course were supplemented by review of the electronic medical record. Nine children with SRSE who had KD initiated in the PICU were identified. Descriptive analysis was performed. Mean age was 5.4 years (SD 2.24). Median number of days to start KD from detection of seizures was 13 [interquartile range (IQR) 10-16]. Mean time to achieve ketosis was 4.2 days (SD 3.4). The median number of antiepileptic drugs (AEDs) trialed before KD was started was 4 [IQR 3-4], and the median number of continuous infusions was 2 [IQR 2-3]. After initiation of KD, most patients were weaned off anesthetic infusions by 1 week. Outcomes were variable. We demonstrated the feasibility of a practical approach to initiation of KD for children with SRSE. These children were successfully weaned off continuous anesthetic infusions. Larger studies are needed to determine effectiveness, safety, and tolerability of KD in the management of SRSE as well as ease of implementation.

  11. Efficacy and safety of vedolizumab as a treatment option for moderate to severe refractory ulcerative colitis in two patients after liver transplant due to primary sclerosing cholangitis.

    PubMed

    Olmedo Martín, Raúl Vicente; Amo Trillo, Víctor; González Grande, Rocío; Jiménez Pérez, Miguel

    2017-09-01

    Vedolizumab is a humanized IgG1 monoclonal antibody that selectively blocks the lymphocyte integrin α4β7 and prevents its interaction with endothelial adhesion molecules and subsequent transmigration to the gastrointestinal tract. The drug was approved in 2014 for the induction and maintenance treatment of ulcerative colitis and moderate to severe Crohn's disease that is refractory or intolerant to conventional treatment with corticoids and immunosuppressants and/or anti-TNFα drugs. However, inflammatory bowel disease has a variable behavior following liver transplant. One third of patients with ulcerative colitis associated with primary sclerosing cholangitis are expected to deteriorate despite receiving immunosuppression to prevent rejection. There is limited experience with anti-TNFα agents in patients with inflammatory bowel disease in the setting of liver transplantation and the studies to date involve a limited number of cases. The efficacy and safety data of vedolizumab in this situation are unreliable and very preliminary. We present two cases with the aim to present the efficacy and safety of vedolizumab after one year of treatment in two patients who underwent a transplant due to primary sclerosing cholangitis. One case had de novo post-transplant ulcerative colitis refractory to two anti-TNFα drugs (golimumab and infliximab). The other patient had a colostomy due to fulminant colitis and developed severe ulcerative proctitis refractory to infliximab after reconstruction with an ileorectal anastomosis.

  12. Therapeutic Hypothermia for Refractory Status Epilepticus in a Child with Malignant Migrating Partial Seizures of Infancy and SCN1A Mutation: A Case Report

    PubMed Central

    Shein, Steven L.; Reynolds, Thomas Q.; Gedela, Satyanarayana; Kochanek, Patrick M.

    2012-01-01

    Status epilepticus (SE) is a common indication for neurocritical care and can be refractory to standard measures. Refractory SE (RSE) is associated with high morbidity and mortality. Unconventional therapies may be utilized in certain cases, including therapeutic hypothermia (TH), bumetanide, and the ketogenic diet. However, the literature describing the use of such therapies in RSE is limited. Details of a case of TH for RSE in an infant with malignant migrating partial seizures of infancy were obtained from the medical record. A 4-month-old child developed SE that was refractory to treatment with concurrent midazolam, phenobarbital, fosphenytoin, topiramate, levetiracetam, folinic acid, and pyridoxal-5-phosphate. This led to progressive implementation of three unconventional therapies: TH, bumetanide, and the ketogentic diet. Electrographic seizures ceased for the entirety of a 43-hour period of TH with a target rectal temperature of 33.0°C–34.0°C. No adverse effects of hypothermia were noted other than a single episode of asymptomatic hypokalemia. Seizures recurred 10 hours after rewarming was begun and did not abate with reinstitution of hypothermia. No effect was seen with administration of bumetanide. Seizures were controlled long-term within 48 hours of institution of the ketogenic diet. TH and the ketogenic diet may be effective for treating RSE in children. PMID:23667778

  13. Infliximab versus Cyclosporine Treatment for Severe Corticosteroid-Refractory Ulcerative Colitis: A Korean, Retrospective, Single Center Study

    PubMed Central

    Kim, Eun Hye; Kim, Duk Hwan; Park, Soo Jung; Hong, Sung Pil; Kim, Tae Il; Kim, Won Ho; Cheon, Jae Hee

    2015-01-01

    Background/Aims In patients with corticosteroid-refractory ulcerative colitis (UC), cyclosporine or infliximab may be added to the treatment regimen to induce remission. Here, we aimed to compare the efficacy of cyclosporine and infliximab. Methods Between January 1995 and May 2012, the medical records of 43 patients with corticosteroid-refractory UC who received either infliximab or cyclosporine as a rescue therapy at a tertiary care hospital in Korea were reviewed. Results Among the 43 patients, 10 underwent rescue therapy with cyclosporine and the remaining 33 patients received infliximab. A follow-up of 12 months was completed for all patients. The colectomy rate at 12 months was 30% and 3% in the cyclosporine and the infliximab groups, respectively (p=0.034). However, the Cox proportional hazard model indicated that the treatment of rescue therapy was not an independent associate factor for preventing colectomy (p=0.164). In the subgroup analysis, infliximab with azathioprine was superior to cyclosporine for preventing colectomy (hazard ratio of infliximab with azathioprine compared with cyclosporine only, 0.073; 95% confidence interval, 0.008 to 0.629). Conclusions No difference between infliximab and cyclosporine with respect to preventing colectomy was noted. However, infliximab with azathioprine may be more effective than cyclosporine alone for preventing colectomy. PMID:25473080

  14. 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.

  15. 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

  16. 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.

  17. Refractory Ulcerative Colitis Treatment

    PubMed Central

    Green, Jesse A.

    2007-01-01

    Treatment of refractory ulcerative colitis (UC) is a common clinical challenge. In either acute or chronic refractory UC, the disease may continue to remain active, even though the patient is on appropriate therapy. It is important to reassess and characterize the patient's disease before adding new medications to the current medical regimen. After determining the current extent and severity of the UC—ruling out other causes of bloody diarrhea and determining what complications are present—new treatment approaches can then be started. It is critical to first optimize oral 5-aminosalicylic acid (5-ASA) therapy combined with rectal 5-ASA or corticosteroid suppositories, plus corticosteroid or 5-ASA enemas or foam preparations. Oral or intravenous corticosteroids are appropriate to use if needed, but alternative approaches must be used for long-term maintenance. 6-Mercaptopurine (6-MP) or azathioprine can be very helpful for severe chronic refractory UC. In those patients who do not respond to 5-ASA medications, corticosteroids, and 6-MP or azathioprine, infliximab offers an important approach for induction and maintenance of remission for refractory chronic ulcerative colitis as well as for select cases of refractory acute UC. Cyclosporine use is an alternative medical approach for the refractory acute UC patient. Colectomy with ileal pouch-anal anastomosis remains a valuable option for the refractory chronic or acute UC patient, because it can provide both a “cure” for the disease, as well as eliminate ineffective medications with their associated side effects. PMID:21960779

  18. High-volume hemofiltration and prone ventilation in subarachnoid hemorrhage complicated by severe acute respiratory distress syndrome and refractory septic shock

    PubMed Central

    Cornejo, Rodrigo; Romero, Carlos; Ugalde, Diego; Bustos, Patricio; Diaz, Gonzalo; Galvez, Ricardo; Llanos, Osvaldo; Tobar, Eduardo

    2014-01-01

    We report the successful treatment of two patients with aneurismal subarachnoid hemorrhage complicated by severe respiratory failure and refractory septic shock using simultaneous prone position ventilation and high-volume hemofiltration. These rescue therapies allowed the patients to overcome the critical situation without associated complications and with no detrimental effects on the intracranial and cerebral perfusion pressures. Prone position ventilation is now an accepted therapy for severe acute respiratory distress syndrome, and high-volume hemofiltration is a non-conventional hemodynamic support that has several potential mechanisms for improving septic shock. In this manuscript, we briefly review these therapies and the related evidence. When other conventional treatments are insufficient for providing safe limits of oxygenation and perfusion as part of basic neuroprotective care in subarachnoid hemorrhage patients, these rescue therapies should be considered on a case-by-case basis by an experienced critical care team. PMID:25028955

  19. Complete recovery after severe myxoedema coma complicated by status epilepticus.

    PubMed

    Fjølner, Jesper; Søndergaard, Esben; Kampmann, Ulla; Nielsen, Søren

    2015-03-25

    We report a case of life-threatening myxoedema presenting with hypothermia, hypotension, bradycardia, pericardial effusion and deep coma. The condition was complicated by prolonged status epilepticus. The optimal treatment strategy has been debated over the years and the literature is briefly reviewed. Treatment with l-thyroxine (LT4) monotherapy without initial loading dose and with no l-triiodothyronine (LT3) treatment was successful with full recovery after hospitalisation for more than a month. Myxoedema coma is a rare, reversible condition with a high mortality and should be considered as a differential diagnosis in medical emergencies. 2015 BMJ Publishing Group Ltd.

  20. Refractory recycling

    SciTech Connect

    Oxnard, R.T. )

    1994-10-01

    Businesses are run by profit and opportunity. Businesses will not recycle or reduce waste unless it is profitable, mandatory or perceived to be either in the future. Pressure from investors, government, consumers and accountants will increase the importance of recycling of refractories. The history and trends of refractory recycling and a method for auditing waste is discussed in this article.

  1. Refractory duodenal ulcer.

    PubMed Central

    Bardhan, K D

    1984-01-01

    A refractory duodenal ulcer was arbitrarily defined as one that had failed to heal completely after treatment with cimetidine 1 g daily for three months. Of 66 patients with refractory duodenal ulcer, healing eventually occurred in 37 patients, after treatment for an average of 7.4 months. But 28 patients did not heal despite treatment for an average of 9.4 months; and one patient defaulted. In 41 patients the daily dose of cimetidine was increased to 2 g: the ulcers in 31 patients healed. In eight patients the daily dose was increased to 3 g and healing occurred in four patients. Eighteen patients required admission on 22 occasions because of severe symptoms despite treatment. Nine patients underwent surgery but in five the results were poor. Differences in clinical and endoscopic features between refractory and non-refractory ulcer patients were small. Acid and pepsin secretion were similar and gastrin concentrations normal. Blood levels of the drug and suppression of acid secretion were both satisfactory. Identification of refractory ulcer patients at the start of treatment was therefore not possible. Refractoriness could occur at any time during the course of the disease, previous treatment with cimetidine often having resulted in rapid healing, but subsequent relapses were also usually refractory. The cause of refractoriness remains unknown and the rather poor results of surgery in this series suggests that optimal management of these patients remains to be determined. Refractoriness probably indicates a changed natural history of the disease and in some patients a more poor prognosis. PMID:6428982

  2. Refractory Plasmonics without Refractory Materials.

    PubMed

    Albrecht, Gelon; Kaiser, Stefan; Giessen, Harald; Hentschel, Mario

    2017-10-11

    Refractory plasmonics deals with metallic nanostructures that can withstand high temperatures and intense laser pulses. The common belief was that refractory materials such as TiN are necessary for this purpose. Here we show that refractory plasmonics is possible without refractory materials. We demonstrate that gold nanostructures which are overcoated with 4 and 40 nm Al2O3 (alumina) by an atomic layer deposition process or by thick IC1-200 resist can withstand temperatures of over 800 °C at ambient atmospheric conditions. Furthermore, the alumina-coated structures can withstand intense laser radiation of over 10 GW/cm(2) at ambient conditions without damage. Thus, it is possible to combine the excellent linear and nonlinear plasmonic properties of gold with material properties that were believed to be only possible with the lossier and less nonlinear refractory materials.

  3. Comparisons of subgingival microbial profiles of refractory periodontitis, severe periodontitis, and periodontal health using the human oral microbe identification microarray.

    PubMed

    Colombo, Ana Paula V; Boches, Susan K; Cotton, Sean L; Goodson, J Max; Kent, Ralph; Haffajee, Anne D; Socransky, Sigmund S; Hasturk, Hatice; Van Dyke, Thomas E; Dewhirst, Floyd; Paster, Bruce J

    2009-09-01

    This study compared the subgingival microbiota of subjects with refractory periodontitis (RP) to those in subjects with treatable periodontitis (GRs = good responders) or periodontal health (PH) using the Human Oral Microbe Identification Microarray (HOMIM). At baseline, subgingival plaque samples were taken from 47 subjects with periodontitis and 20 individuals with PH and analyzed for the presence of 300 species by HOMIM. The subjects with periodontitis were classified as having RP (n = 17) based on mean attachment loss (AL) and/or more than three sites with AL >or=2.5 mm after scaling and root planing, surgery, and systemically administered amoxicillin and metronidazole or as GRs (n = 30) based on mean attachment gain and no sites with AL >or=2.5 mm after treatment. Significant differences in taxa among the groups were sought using the Kruskal-Wallis and chi(2) tests. More species were detected in patients with disease (GR or RP) than in those without disease (PH). Subjects with RP were distinguished from GRs or those with PH by a significantly higher frequency of putative periodontal pathogens, such as Parvimonas micra (previously Peptostreptococcus micros or Micromonas micros), Campylobacter gracilis, Eubacterium nodatum, Selenomonas noxia, Tannerella forsythia (previously T. forsythensis), Porphyromonas gingivalis, Prevotella spp., Treponema spp., and Eikenella corrodens, as well as unusual species (Pseudoramibacter alactolyticus, TM7 spp. oral taxon [OT] 346/356, Bacteroidetes sp. OT 272/274, Solobacterium moorei, Desulfobulbus sp. OT 041, Brevundimonas diminuta, Sphaerocytophaga sp. OT 337, Shuttleworthia satelles, Filifactor alocis, Dialister invisus/pneumosintes, Granulicatella adiacens, Mogibacterium timidum, Veillonella atypica, Mycoplasma salivarium, Synergistes sp. cluster II, and Acidaminococcaceae [G-1] sp. OT 132/150/155/148/135) (P <0.05). Species that were more prevalent in subjects with PH than in patients with periodontitis included Actinomyces

  4. Management of severe sepsis: advances, challenges, and current status.

    PubMed

    Martin-Loeches, Ignacio; Levy, Mitchell M; Artigas, Antonio

    2015-01-01

    The complexity of treating severe sepsis and septic shock has been elucidated in myriad studies, particularly in the past 10 years. The development of clinical guidelines, insight into the effect of bundle elements, and results of clinical trials have brought to light further opportunities and questions in the approach to pharmaceutical interventions for the global challenge to save lives and reduce healthcare costs. Therapeutic interventions including fluid resuscitation, hemodynamic monitoring, glycemic control, corticosteroids, and antimicrobial therapy and stewardship inform outcomes. Research on biomarkers, use of mesenchymal stem cells, blood purification, immunoglobulins, and antioxidative treatments apropos the immune response may soon yield viable therapies.

  5. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status.

    PubMed

    Cortes, Jorge E; Kantarjian, Hagop; Foran, James M; Ghirdaladze, Darejan; Zodelava, Mamia; Borthakur, Gautam; Gammon, Guy; Trone, Denise; Armstrong, Robert C; James, Joyce; Levis, Mark

    2013-10-10

    FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations in acute myeloid leukemia (AML) are associated with early relapse and poor survival. Quizartinib potently and selectively inhibits FLT3 kinase activity in preclinical AML models. Quizartinib was administered orally at escalating doses of 12 to 450 mg/day to 76 patients (median age, 60 years; range, 23 to 86 years; with a median of three prior therapies [range, 0 to 12 therapies]), enrolled irrespective of FLT3-ITD mutation status in a phase I, first-in-human study in relapsed or refractory AML. Responses occurred in 23 (30%) of 76 patients, including 10 (13%) complete remissions (CR) of any type (two CRs, three CRs with incomplete platelet recovery [CRp], five CRs with incomplete hematologic recovery [CRi]) and 13 (17%) with partial remissions (PRs). Of 17 FLT3-ITD-positive patients, nine responded (53%; one CR, one CRp, two CRis, five PRs); of 37 FLT3-ITD-negative patients, five responded (14%; two CRps, three PRs); of 22 with FLT3-ITD-indeterminate/not tested status, nine responded (41%; one CR, three CRis, five PRs). Median duration of response was 13.3 weeks; median survival was 14.0 weeks. The most common drug-related adverse events (> 10% incidence) were nausea (16%), prolonged QT interval (12%), vomiting (11%), and dysgeusia (11%); most were ≤ grade 2. The maximum-tolerated dose was 200 mg/day, and the dose-limiting toxicity was grade 3 QT prolongation. FLT3-ITD phosphorylation was completely inhibited in an in vitro plasma inhibitory assay. Quizartinib has clinical activity in patients with relapsed/refractory AML, particularly those with FLT3-ITD, and is associated with an acceptable toxicity profile.

  6. [Treatment-refractory OCD and its biological pathophysiology].

    PubMed

    Nakao, Tomohiro

    2013-01-01

    Recently, ample evidence has suggested that selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy are highly effective treatments for OCD. There are, however, certain patients who are refractory to almost all types of therapeutic intervention. In recent studies, atypical antipsychotic augmentation of SSRIs and deep brain stimulation have been suggested to be effective for these refractory-type patients. Dysfunction of neuro-circuits throughout the frontal cortex and associated subcortical structures is considered to be due to both serotonergic and dopaminergic nerve system impairment. A large number of previous neuroimaging studies identified abnormally high metabolic activities throughout the frontal cortex as well as subcortical and limbic structures. These over-activities are suggested to be biological markers of the treatment response. In addition, structural and nerve connective dysfunction of these regions may be associated with a severe, treatment-resistant, and treatment-refractory status. A treatment-refractory state may be attributable to the clinical subtypes of OCD. Associations between the symptom subtype and brain activity reveal the heterogeneity of OCD. Several correlative analyses have shown distinct neural correlations associated with specific OCD symptom dimensions such as aggression/checking, contamination/cleaning, and hoarding. Overlapping of these neural disturbances will cause treatment-refractory OCD. Another reason for a treatment-refractory state may be comorbid disorders such as major depression and tic disorders. Comorbid depression will aggravate metabolic impairments in the hippocampus and thalamus and cause more severe disturbance of neuro-circuits in OCD. Obsessive-compulsive symptom with Tourette syndrome or pervasive developmental disorders will become refractory because of fixation caused by developmental factors and a perceptual element called "just right feeling". There should be a close relationship

  7. 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.

  8. Refractory peptic ulcer disease.

    PubMed

    Napolitano, Lena

    2009-06-01

    Refractory PUD is a diagnostic and therapeutic challenge. Optimal management of severe or refractory PUD requires a multidisciplinary team approach, using primary care providers, gastroenterologists, and general surgeons. Medical management has become the cornerstone of therapy. Identification and eradication of H pylori infection combined with acid reduction regimens can heal ulceration and also prevent recurrence. Severe, intractable or recurrent PUD and associated complications mandates a careful and methodical evaluation and management strategy to determine the potential etiologies and necessary treatment (medical or surgical) required.

  9. 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.

  10. -C Refractories

    NASA Astrophysics Data System (ADS)

    Xu, Yibiao; Sang, Shaobai; Li, Yawei; Ren, Bo; Zhao, Lei; Li, Yuanbing; Li, Shujing

    2014-06-01

    Al2O3-C refractories were first fabricated in a coke bed at 1673 K (1400 °C) using tabular corundum, reactive alumina, carbon black, silicon, and microsilica as the starting materials and phenol resin as the binder. Then the alkali attack resistance of those materials was conducted in the powder mixture of carbon black and potassium carbonate (1:1 wt pct) in a graphite crucible at 1273 K (1000 °C) for 10 hours. The correlation between pore size, permeability of Al2O3-C refractories, and their alkali (K2CO3) attack was investigated by means of mercury intrusion porosimetry, X-ray diffraction (XRD), and scanning electron microscopy (SEM). The results showed that the pore structure of Al2O3-C refractories was controlled by the addition of silicon, ultrafine reactive alumina, and microsilica to in-situ form SiC whiskers and mullite in the preparation process. The mean pore size of Al2O3-C refractories was strongly associated with permeability. With the decrease of the mean pore size, the permeability of the Al2O3-C refractories reduced constantly. The alkali attack test also verified that the Al2O3-C refractories with lower permeability had better alkali corrosion resistance, because the penetration of K vapor into the materials could be restricted effectively. The corrosion mechanism of Al2O3-C refractories supposes that (1) K2CO3 was reduced to K vapor and penetrated into the specimen through the open pores and (2) K vapor reacted with SiC, SiO2, and alumina to form KAlSi2O6 and KAlSiO4, which is in agreement with the thermodynamic prediction.

  11. Pre-operative fibrous osteodystrophy and severe, refractory, post-operative hypocalcemia following parathyroidectomy in a dog

    PubMed Central

    Reinhart, Jennifer M.; Nuth, Ellie K.; Byers, Christopher G.; Thoesen, Mike; Armbrust, Laura J.; Biller, David S.; Harkin, Kenneth R.

    2015-01-01

    A 13-year-old dog exhibited dramatic, radiographic osteopenia consistent with fibrous osteodystrophy secondary to primary hyperparathyroidism. Following parathyroidectomy, the dog developed severe, prolonged hypocalcemia, but was successfully treated and discharged 32 d after surgery. A variety of factors may have contributed to this dog’s hypocalcemia including hypoparathyroidism and hungry bone syndrome. PMID:26246635

  12. Pre-operative fibrous osteodystrophy and severe, refractory, post-operative hypocalcemia following parathyroidectomy in a dog.

    PubMed

    Reinhart, Jennifer M; Nuth, Ellie K; Byers, Christopher G; Thoesen, Mike; Armbrust, Laura J; Biller, David S; Harkin, Kenneth R

    2015-08-01

    A 13-year-old dog exhibited dramatic, radiographic osteopenia consistent with fibrous osteodystrophy secondary to primary hyperparathyroidism. Following parathyroidectomy, the dog developed severe, prolonged hypocalcemia, but was successfully treated and discharged 32 d after surgery. A variety of factors may have contributed to this dog's hypocalcemia including hypoparathyroidism and hungry bone syndrome.

  13. 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…

  14. 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…

  15. Failure of Fecal Microbiota Transplantation in a Three-Year-Old Child with Severe Refractory Ulcerative Colitis

    PubMed Central

    Yokoyama, Koji; Imagawa, Tomoyuki; Inoue, Shun; Tulyeu, Janyerkye; Tanaka, Mamoru; Yamagata, Takanori

    2016-01-01

    Fecal microbiota transplantation (FMT) is a treatment designed to correct gut dysbiosis by administration of feces from a healthy volunteer. It is still unclear whether FMT for children with ulcerative colitis (UC) is effective or hazardous. Here we describe a young patient to have received FMT for UC. A three-year-old girl was admitted to our hospital with severe active UC, and treated with aminosalicylates and various immunosuppressive drugs. As remission was not achieved, we decided to try FMT before colectomy. We administered donor fecal material a total of six times by retention enema (×2) and via a nasoduodenal tube (×4) within 10 days. The patient developed abdominal pain and pyrexia after each FMT session. Analyses revealed the transferred donor fecal microbiota had not been retained by the patient, who ultimately underwent colectomy. The severity of the UC and/or timing of FMT may have partly accounted for the poor outcome. PMID:27738605

  16. Successful surgical management of New Onset Refractory Status Epilepticus (NORSE) presenting with gelastic seizures in a 3 year old girl.

    PubMed

    Marashly, Ahmad; Lew, Sean; Koop, Jennifer

    2017-01-01

    Gelastic seizures (GS) are typically associated with hypothalamic hamartomas and present during childhood. However it is now known that GS can be found in focal epilepsies arising from other regions in the brain, including mesial and neocortical frontal, temporal and parietal regions. GS have rarely been described as the presenting manifestation of New Onset Refractory Status Epilepticus (NORSE). In this article we describe a previously healthy 3-year-old who presented with an explosive onset of GS that were refractory to multiple anti-seizure medications. These seizures arose from the right frontal region. An extensive metabolic and immunological evaluation was negative. Her brain magnetic resonance imaging (MRI) was negative, however the Positron Emission Tomography (PET) scan showed a hypermetabolic region in the right frontal inferior gyrus. She underwent a depth electrode evaluation that revealed a widespread irritative zone involving the PET "lesion" as well as mesial and neocortical regions in the right frontal lobe. The seizure onset zone was widespread and non-localizable. However the GS were associated with a clear ictal epileptiform discharge on invasive EEG arising from the depth of the superior frontal gyrus, which was not overlapping with the PET hypermetabolic region. She underwent a right frontal lobectomy sparing the primary motor region in the pre-central gyrus. She has remained seizure free for 15 months since. The pathological analysis showed focal cortical dysplasia type II in the region of the PET scan hypermetabolism. This case expands the clinical spectrum of GS to include cases of NORSE. Additionally the case highlights the role of resective surgery in GS presenting as NORSE and the potentially excellent outcome that can be achieved by early intervention.

  17. 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.

  18. Theoretical and practical issues related to the management of severe and refractory psychotic illness complicated by pulmonary embolism

    PubMed Central

    Chandele, Payal H.; Cholera, Rashmin; Kale, Sanjiv; Ramakrishnan, Aparna; Ross, Cecil R.; Andrade, Chittaranjan

    2015-01-01

    Pulmonary embolism (PE) is a potentially fatal condition. We describe the educative case of a young adult male, with a longstanding history of schizophrenia, who was receiving anticoagulant treatment because of repeated episodes of PE in the past. He presented with severe exacerbation of psychosis and did not respond to oral and parenteral antipsychotic medication during inpatient treatment. He was taken up for electroconvulsive therapy (ECT) and received a single ECT uneventfully. The ECT course had to be interrupted because of the unexpected development of a 4-day febrile illness, after which he experienced sudden onset breathlessness, which was diagnosed as acute-on-chronic PE. After the crisis resolved with 4 days of intensive care, he was managed with clozapine. We discuss concerns associated with the psychiatric management of patients with PE; special issues include the use of restraints, parenteral antipsychotic medications, anticoagulants, and ECT. PMID:26816433

  19. Refractory celiac disease.

    PubMed

    Malamut, Georgia; Cellier, Christophe

    2014-03-01

    A small subset of celiac disease (CD) patients becomes refractory to a gluten-free diet with persistent malabsorption and intestinal villous atrophy. Diagnosis of this condition defined as refractory celiac disease (RCD) is made after exclusion of other small bowel diseases with villous atrophy. RCD has been subdivided into two subgroups according to the normal or abnormal phenotype of intraepithelial lymphocytes. Whereas normal RCD is hardly distinguishable from active CD, abnormal RCD has a severe clinical presentation and a very poor prognosis. We precisely describe below the different types of RCD and propose diagnostic and therapeutic guidelines for its clinical management.

  20. Severe Developmental B Lymphopoietic Defects in Foxp3-Deficient Mice are Refractory to Adoptive Regulatory T Cell Therapy.

    PubMed

    Riewaldt, Julia; Düber, Sandra; Boernert, Marie; Krey, Martina; Dembinski, Marcin; Weiss, Siegfried; Garbe, Annette I; Kretschmer, Karsten

    2012-01-01

    The role of Foxp3-expressing regulatory T (T(reg)) cells in tolerance and autoimmunity is well-established. However, although of considerable clinical interest, the role of T(reg) cells in the regulation of hematopoietic homeostasis remains poorly understood. Thus, we analysed B and T lymphopoiesis in the scurfy (Sf) mouse model of T(reg) cell deficiency. In these experiments, the near-complete block of B lymphopoiesis in the BM of adolescent Sf mice was attributed to autoimmune T cells. We could exclude a constitutive lympho-hematopoietic defect or a B cell-intrinsic function of Foxp3. Efficient B cell development in the BM early in ontogeny and pronounced extramedullary B lymphopoietic activity resulted in a peripheral pool of mature B cells in adolescent Sf mice. However, marginal zone B and B-1a cells were absent throughout ontogeny. Developmental B lymphopoietic defects largely correlated with defective thymopoiesis. Importantly, neonatal adoptive T(reg) cell therapy suppressed exacerbated production of inflammatory cytokines and restored thymopoiesis but was ineffective in recovering defective B lymphopoiesis, probably due to a failure to compensate production of stroma cell-derived IL-7 and CXCL12. Our observations on autoimmune-mediated incapacitation of the BM environment in Foxp3-deficient mice will have direct implications for the rational design of BM transplantation protocols for patients with severe genetic deficiencies in functional Foxp3(+) T(reg) cells.

  1. Severe Developmental B Lymphopoietic Defects in Foxp3-Deficient Mice are Refractory to Adoptive Regulatory T Cell Therapy

    PubMed Central

    Riewaldt, Julia; Düber, Sandra; Boernert, Marie; Krey, Martina; Dembinski, Marcin; Weiss, Siegfried; Garbe, Annette I.; Kretschmer, Karsten

    2012-01-01

    The role of Foxp3-expressing regulatory T (Treg) cells in tolerance and autoimmunity is well-established. However, although of considerable clinical interest, the role of Treg cells in the regulation of hematopoietic homeostasis remains poorly understood. Thus, we analysed B and T lymphopoiesis in the scurfy (Sf) mouse model of Treg cell deficiency. In these experiments, the near-complete block of B lymphopoiesis in the BM of adolescent Sf mice was attributed to autoimmune T cells. We could exclude a constitutive lympho-hematopoietic defect or a B cell-intrinsic function of Foxp3. Efficient B cell development in the BM early in ontogeny and pronounced extramedullary B lymphopoietic activity resulted in a peripheral pool of mature B cells in adolescent Sf mice. However, marginal zone B and B-1a cells were absent throughout ontogeny. Developmental B lymphopoietic defects largely correlated with defective thymopoiesis. Importantly, neonatal adoptive Treg cell therapy suppressed exacerbated production of inflammatory cytokines and restored thymopoiesis but was ineffective in recovering defective B lymphopoiesis, probably due to a failure to compensate production of stroma cell-derived IL-7 and CXCL12. Our observations on autoimmune-mediated incapacitation of the BM environment in Foxp3-deficient mice will have direct implications for the rational design of BM transplantation protocols for patients with severe genetic deficiencies in functional Foxp3+ Treg cells. PMID:22679447

  2. Severe Enteropathy and Hypogammaglobulinemia Complicating Refractory Mycobacterium tuberculosis Complex Disseminated Disease in a Child with IL-12Rβ1 Deficiency.

    PubMed

    Arias, Andrés Augusto; Perez-Velez, Carlos M; Orrego, Julio César; Moncada-Velez, Marcela; Rojas, Jessica Lineth; Wilches, Alejandra; Restrepo, Andrea; Trujillo, Mónica; Garcés, Carlos; Arango-Ferreira, Catalina; González, Natalia; Oleaga-Quintas, Carmen; Fernández, Diana; Isaza-Correa, Johana Marcela; Gongóra, Diego Eduardo; Gonzalez-Loaiza, Daniel; Sierra, Juan Esteban; Casanova, Jean Laurent; Bustamante, Jacinta; Franco, José Luis

    2017-09-01

    Mendelian susceptibility to mycobacterial disease is a rare clinical condition characterized by a predisposition to infectious diseases caused by poorly virulent mycobacteria. Other infections such as salmonellosis and candidiasis are also reported. The purpose of this article is to describe a young boy affected with various infectious diseases caused by Mycobacterium tuberculosis complex, Salmonella sp, Klebsiella pneumonie, Citrobacter sp., and Candida sp, complicated with severe enteropathy and transient hypogammaglobulinemia. We reviewed medical records and performed flow cytometry staining for lymphocyte populations, lymphocyte proliferation in response to PHA, and intracellular IFN-γ production in T cell PHA blasts in the patient and a healthy control. Sanger sequencing was used to confirm the genetic variants in the patient and relatives. Genetic analysis revealed a bi-allelic mutation in IL12RB1 (C291Y) resulting in complete IL-12Rβ1 deficiency. Functional analysis demonstrated the lack of intracellular production of IFN-γ in CD3+ T lymphocytes from the patient in response to rhIL-12p70. To our knowledge, this is the third patient with MSMD due to IL-12Rβ1 deficiency complicated with enteropathy and hypogammaglobulinemia and the first case of this disease to be described in Colombia.

  3. New-onset refractory status epilepticus in an adult with an atypical presentation of cat-scratch disease: successful treatment with high-dose corticosteroids.

    PubMed

    Laswell, Emily M; Chambers, Kasandra D; Whitsel, Danielle R; Poudel, Kiran

    2015-06-01

    New-onset refractory status epilepticus (NORSE) is defined as a sudden onset of refractory status epilepticus in patients who do not have a history of epilepsy. It is a neurologic emergency, and determining the underlying etiology is an important factor for effectively managing and predicting the prognosis of NORSE. We describe the case of a 28-year-old woman who was hospitalized with NORSE secondary to an unknown etiology. She did not respond to traditional anticonvulsant therapy, including benzodiazepines, fosphenytoin, propofol, and levetiracetam. The patient was placed on continuous electroencephalography (EEG) monitoring and was treated further with multiple antiepileptics, which were titrated aggressively based on EEG readings and therapeutic drug levels; despite this treatment, EEG monitoring revealed continued seizures. Thus, high-dose corticosteroids were started for seizure control. Her workup included computed tomography and magnetic resonance imaging of the head, a lumbar puncture, toxicology screening, and extensive testing for multiple infectious and inflammatory etiologies. The patient's history revealed recent exposure to a new cat. Serologic results were positive for Bartonella henselae, and she was diagnosed with cat-scratch disease (CSD). She did not have the typical presentation of symptoms of lymphadenopathy, however, which is common in CSD. Doxycycline 100 mg and rifampin 300 mg twice daily were added to the patient's anticonvulsant and corticosteroid therapy. She was hospitalized for a total of 26 days and discharged with only minor neurologic impairment (short-term memory deficits and minor cognitive problems). The patient was discharged receiving antiepileptics, antibiotics, and a corticosteroid taper. To our knowledge, this is the first clinically known case of NORSE secondary to CSD without typical CSD symptoms in the adult population. The patient failed to respond to traditional anticonvulsant therapy alone. With the addition of high

  4. 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.

  5. A prospective, randomized, multicentre trial for the treatment of refractory status epilepticus; experiences from evaluating the effect of the novel drug candidate, NS1209.

    PubMed

    Sabers, Anne; Wolf, Peter; Møller, Arne; Rysgaard, Karen; Ben-Menachem, Elinor

    2013-09-01

    Refractory status epilepticus (RSE) is a life-threatening condition that requires immediate and aggressive treatment. Unfortunately, sometimes standard antiepileptic treatment is insufficient. Furthermore, alternative therapeutic options are limited by low evidence of efficacy. The primary objective of this study was to evaluate the effects of the novel drug candidate, NS1209 versus third-line standard treatment (phenytoin/valproate) for RSE. Having not reached the study end-points, the purpose of this paper is to discuss the challenges that are encountered in conducting a controlled study of RSE. This was a phase II, prospective, multicentre, single-blinded, randomized clinical trial and included patients to two separate protocols for convulsive and non-convulsive RSE (NS1209-006 and NS1209-007). In total, 28 patients were included and 14 patients were exposed to NS1209. At study conclusion, the study was insufficiently powered to detect any statistically significant difference between the two treatment groups. This was especially true for the convulsive RSE protocol. We conclude that high-quality studies in RSE are difficult to conduct owing to a number of ethical and practical problems associated with this critical illness. Challenges for further studies are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Refractory anemia with ringed sideroblasts associated with thrombocytosis: comparative analysis of marked with non-marked thrombocytosis, and relationship with JAK2 V617F mutational status.

    PubMed

    Raya, J M; Arenillas, L; Domingo, A; Bellosillo, B; Gutiérrez, G; Luño, E; Piñán, M A; Barbón, M; Pérez-Sirvent, M L; Muruzábal, M J; Yánez, L; García, L; Lemes, A; Navarro, J T; Elosegi, A; Cortés, M A; Villegas, A; Durán, M A; Ardanaz, M; Florensa, L

    2008-11-01

    The World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues (2001) defined a provisional entity named refractory anemia with ringed sideroblasts associated to marked thrombocytosis (RARS-MT). Diagnosis of RARS-MT requires more than 15% of ringed sideroblasts in bone marrow aspirate and the existence of a thrombocytosis in blood, with a platelet count above 600 x 10(9)/L. Nevertheless, controversy exists regarding this platelet count "cut-off" value and, when RARS-MT was defined, the JAK2 mutation and its importance in the study of myeloproliferative disorders was unknown. We present the results of a Spanish retrospective multicentric study, which includes 76 cases of RARS with associated thrombocytosis (platelet count above 400 x 10(9)/L) at diagnosis (RARS-T), 36 of them with a platelet count above 600 x 10(9)/L. Our aim was to analyze their clinical, analytical and morphological characteristics, and to establish correlations with the JAK2 mutational status.

  7. Refractory Ascites

    PubMed Central

    Siqueira, Fabiolla; Kelly, Traci

    2009-01-01

    Refractory ascites is defined as ascites that does not recede or that recurs shortly after therapeutic paracentesis, despite sodium restriction and diuretic treatment. To date, there is no approved medical therapy specifically for refractory ascites. Management of these patients is based upon procedures such as large-volume paracentesis and transjugular intrahepatic portosystemic shunts (TIPS), which temporarily alleviate symptoms but are not curative. These patients have a poor prognosis and are at risk for a series of complications that are associated with the condition or are secondary to therapy. The most common complications include spontaneous bacterial peritonitis, hepatic hydrothorax, spontaneous bacterial empyema, and umbilical hernia. The predicted survival rate is as low as 50% at 1 year, and prognosis worsens as patients present with comorbidities such as hepatorenal syndrome, renal failure, and hepatocellular carcinoma. The only curative treatment is liver transplantation, though current studies have shown that TIPS also increases survival.

  8. Lack of Association between Selenium Status and Disease Severity and Activity in Patients with Graves' Ophthalmopathy

    PubMed Central

    Dehina, Nora; Hofmann, Peter Josef; Behrends, Thomas; Eckstein, Anja; Schomburg, Lutz

    2016-01-01

    Background Selenium (Se) is of importance for regular functioning of the immune system and thyroid gland, and may have a health effect in mild Graves' ophthalmopathy (GO). Objective As the Se status declines in inflammation, we analyzed whether GO activity or severity affects the Se status of patients. Methods Serum Se and selenoprotein P (SePP) concentrations were retrospectively determined in 84 consecutive GO patients before treatment and compared to their clinical activity score (CAS) and severity of eye changes (NOSPECS) status, and to the concentrations of autoantibodies targeting the TSH receptor (TRAK) or the IGF1 receptor (IGF1R-aAB). Results Serum Se and SePP were linearly associated, indicating a suboptimal Se status of our patients. In comparison to data from other European cohorts, the majority of GO patients had a relatively poor Se status ([Se] ± SD; 70.0 ± 23.8 µg/l), below the threshold needed for full expression of selenoproteins. TRAK were inversely associated with Se concentrations, while IGF1R-aAB titers were not associated with Se. Neither Se nor SePP concentrations differed between GO patients with severe versus mild or active versus inactive disease, or showed significant associations with the CAS or NOSPECS values. Conclusion GO patients are at risk of a low Se status, yet disease severity or activity does not seem to affect Se or SePP concentrations directly. However, as the retrospective nature of the analysis does not allow conclusions on a potential causative role of Se on Graves' disease or GO risk, these results neither support nor discourage adjuvant Se supplementation attempts. PMID:27099840

  9. Association between nutritional status and severity of dengue infection in children in El Salvador.

    PubMed

    Marón, Gabriela M; Clará, A Wilfrido; Diddle, John Wesley; Pleités, Ernesto B; Miller, Laura; Macdonald, Gene; Adderson, Elisabeth E

    2010-02-01

    Clinical observations and some studies suggest that dengue virus infection is more severe among children with better nutritional status. We examined the nutritional status of children in El Salvador and its relationship between this and the severity of dengue infection. Z-scores for weight-for-age, height-for-age, and body mass index (BMI)-for-age of children with dengue fever (66), dengue hemorrhagic fever (62), and healthy controls (74) were compared. There were no differences in weight-for-age or BMI-for-age Z-scores between the three groups. Children with dengue fever had a greater height-for-age than healthy controls but no significant differences in rates of stunting. There was no difference in height between children with dengue fever and dengue hemorrhagic fever. Excess nutrition does not appear to be a risk factor for severe forms of dengue infection in El Salvador, nor does malnutrition appear to be predictive of good outcomes.

  10. Validity of caregiver information on the developmental status of severely brain-damaged young children.

    PubMed

    Stancin, T; Reuter, J; Dunn, V; Bickett, L

    1984-01-01

    Two studies were conducted to examine the validity of caregiver information on the developmental status of severely brain-damaged young children. First, developmental information on 106 severely brain-damaged young children, obtained from a caregiver-completed behavior inventory--the Kent Infant Development Scale, was compared to that obtained from the Bayley Scales of Infant Development (the Bayley Scales). Developmental age estimates from both tests were highly correlated and similar. Results suggest that it is possible to substitute the Kent Infant Development Scale for the Bayley Scales when measuring the developmental status of severely brain-damaged young children. In a second study examining the differential validity of caregivers' reports, we found that mothers' Kent Infant Development Scales yielded higher developmental age estimates than did teachers' Kent Infant Development Scales.

  11. Effects of mild, moderate and severe closed head injury on long-term vocational status.

    PubMed

    Stambrook, M; Moore, A D; Peters, L C; Deviaene, C; Hawryluk, G A

    1990-01-01

    Survival from significant closed head injury (CHI) is frequently associated with cognitive defects, physical impairment, personality change, interpersonal difficulty and, in general, some degree of social dependence. Here we report a multidimensional assessment of quality of life of a sample of 131 male head-injury patients suffering a range of severities of insult with specific emphasis on vocational outcome. Of those patients who sustained a severe injury and were employed full-time prior to the CHI, only 55% were able to return to this level of employment. No differences were found between the moderate and severe groups in pre- or post-CHI occupational status, as measured by the Blishen (1967) quantitative social economic index, although both groups declined from pre- to post-CHI. Lower post-CHI occupational status was associated with lower GCS on admission and longer lengths of post-traumatic amnesia, with patient self-report of physical, cognitive and psychosocial difficulties, including spousal reports of confusion, belligerance, verbal expansiveness and the decreased ability to perform socially-expected activities. Stepwise multiple regression analysis accounted for 38% of variance in post-injury vocational status, with lower pre-injury vocational status, greater age, high physical and psychological difficulties and lower admission Glasgow Coma Scale score variables forming the regression equation. Implications are discussed in terms of rehabilitation issues, including vocational programming and planning.

  12. Association between poor nutritional status and severe depression in Korean cerebral infarction patients.

    PubMed

    Lim, Hyun Jung; Choue, Ryowon

    2012-01-01

    The purpose of this study was to assess the association between cerebral infarction (CI), nutritional status, and depression. Subjects with and without CI (n = 146; 73 CI vs. 73 non-CI) were recruited from Kyung Hee University Medical Center (Seoul, Korea) and were matched according to age and gender. The subjects' medical histories, health-related behavioral habits, food intake, nutritional assessment, and depression status were analyzed. The prevalence of hypertension or diabetes were much higher in subjects in the CI group than in the non-CI group (P < 0.001). Subjects with CI registered lower dietary intakes of potassium, dietary fiber, fish, fruits, and vegetables than non-CI subjects (P < 0.05). By the mini-nutritional assessment (MNA) classification, malnutrition affected 57.5% of subjects in the CI group, but none of the subjects in the non-CI group (P < 0.001). The average Beck depression inventory (BDI) score was 43.6 ± 7.7 points in the CI group and 20.6 ± 13.1 points in the non-CI group (P < 0.001). Higher MNA scores (well-nourished status) were inversely associated with CI prevalence (odds ratio (OR) = 0.23; 95% CI: 0.07, 0.79) after controlling for age, gender, medical history, and health-related factors, whereas BDI was not associated with CI prevalence (OR = 1.32; 95% CI: 0.90, 1.94). CI patients had several comorbidities, inappropriate health-related behavioral habits, malnourished status, and severe depression prior to CI onset. Indices of well-nourished status were inversely associated with CI. Accordingly, it would be desirable to develop a protocol for medical nutrition therapy in CI patients to improve nutritional status.

  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. The association of socioeconomic status and symptom severity in persons with fibromyalgia.

    PubMed

    Fitzcharles, Mary-Ann; Rampakakis, Emmanouil; Ste-Marie, Peter A; Sampalis, John S; Shir, Yoram

    2014-07-01

    Although persons with lower socioeconomic status (SES) generally have poorer health status for many medical conditions, the association of SES with symptom severity in fibromyalgia (FM) is unknown. The subjective symptoms of FM may be influenced by personal perceptions, and environmental and psychosocial factors. Therefore SES may influence symptom expression and severity. Data for this cross-sectional analysis were obtained from a real-life prospective cohort of 246 patients with FM categorized according to level of education: high school graduates or less (Group 1; n = 99), college graduates (Group 2; n = 84), and university graduates (Group 3; n = 63). The association between level of education, a well-validated measure of SES, and disease severity, functional status, and quality of life were examined. Lower education was significantly associated with older age (p = 0.039), current unemployment (p < 0.001), and more severe disease, as measured by patient global assessment disease activity (p = 0.019), McGill Pain Questionnaire (p = 0.026), Pain Disability Index (p = 0.031), Pain Catastrophizing Scale (p = 0.015), Health Assessment Questionnaire (p = 0.001), and Fibromyalgia Impact Questionnaire (p = 0.002), but not pain level, anxiety, or depression. These associations remained significant even upon adjusting for age and sex differences. Patients with FM and lower SES, as assessed by education level, reported greater symptom severity and functional impairment, despite reporting similar levels of pain, depression, and anxiety. Although FM spans all socioeconomic groups, factors other than specific disease characteristics or mental status, appear to play an important role in patients' perception of illness.

  15. Racial and ethnic differences in the relationship between depression severity and functional status.

    PubMed

    Huang, Frederick Y; Chung, Henry; Kroenke, Kurt; Spitzer, Robert L

    2006-04-01

    Major depression has a negative impact on functional status and quality of life, but little is known about racial or ethnic differences in the relationship between depression and functional disability. This study compared the association between depression severity and functional status among three different racial or ethnic groups. Data were from participants in the original Patient Health Questionnaire (PHQ) Primary Care Study and PHQ Obstetrics-Gynecology Study (N=5,427). Among the study participants, 62.0 percent were non-Hispanic white, 14.8 percent were African American, and 23.1 percent were Latino. Depression severity was assessed with the PHQ-9, the self-administered DSM-IV criteria-based depression module of the PHQ diagnostic instrument for mental disorders. Functional status was measured with the scales of the Medical Outcomes Study 20-item Short Form Health Survey (SF-20), self-reported disability days, clinic visits, and symptom-related difficulty. Groups were compared in terms of mean PHQ-9 scores and functional status at varying levels of depression severity. Linear regression was used to control for age, gender, education level, and language. Mean PHQ-9 scores were not significantly different between the three different racial or ethnic groups. Similar linear associations were found in all three racial or ethnic groups between increasing PHQ-9 scores (more severe depression) and worsening function on the SF-20 scales and an increased number of disability days and clinic visits. Latinos reported significantly less functional impairment on all measures of functionality compared with non-Hispanic whites. Functional impairment increased with increasing levels of depression severity in all three racial or ethnic groups, although Latinos consistently reported fewer functional disturbances compared with non-Hispanic whites.

  16. 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.

  17. Low-socioeconomic-status enrollees in high-deductible plans reduced high-severity emergency care.

    PubMed

    Wharam, J Frank; Zhang, Fang; Landon, Bruce E; Soumerai, Stephen B; Ross-Degnan, Dennis

    2013-08-01

    One-third of US workers now have high-deductible health plans, and those numbers are expected to grow in 2014 as implementation of the Affordable Care Act continues. There is concern that high-deductible health plans might cause enrollees of low socioeconomic status to forgo emergency care as a result of burdensome out-of-pocket costs. We analyzed emergency department (ED) visits and hospitalizations over two years among enrollees insured in high-deductible plans through small employers in Massachusetts. We found that plan members of low socioeconomic status experienced 25-30 percent reductions in high-severity ED visits over both years, while hospitalizations declined by 23 percent in year 1 but rose again in year 2. Similar trends were not found among high-deductible plan members of high socioeconomic status. Our findings suggest that plan members of low socioeconomic status at small firms responded inappropriately to high-deductible plans and that initial reductions in high-severity ED visits might have increased the need for subsequent hospitalizations. Policy makers and employers should consider proactive strategies to educate high-deductible plan members about their benefit structures or identify members at higher risk of avoiding needed care. They should also consider implementing means-based deductibles.

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

    PubMed Central

    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. PMID:26750681

  19. 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.

  20. 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.

  1. Nutritional status as marker for disease activity and severity predicting mortality in patients with systemic sclerosis.

    PubMed

    Krause, Lijana; Becker, Mike O; Brueckner, Claudia S; Bellinghausen, Christina-Julia; Becker, Corinna; Schneider, Udo; Haeupl, Thomas; Hanke, Katharina; Hensel-Wiegel, Karin; Ebert, Heidrun; Ziemer, Sabine; Ladner, Ulf-Müller; Pirlich, Matthias; Burmester, Gerd R; Riemekasten, Gabriela

    2010-11-01

    To assess and analyse nutritional status in patients with systemic sclerosis (SSc) and identify possible associations with clinical symptoms and its prognostic value. Body mass index (BMI) and parameters of bioelectrical impedance analysis (BIA) were assessed in 124 patients with SSc and 295 healthy donors and matched for sex, age and BMI for comparisons. In patients with SSc, BMI and BIA values were compared with clinical symptoms in a cross-sectional study. In a prospective open analysis, survival and changes in the nutritional status and energy uptake induced by nutritional treatment were evaluated. Patients with SSc had reduced phase angle (PhA) values, body cell mass (BCM), percentages of cells, increased extracellular mass (ECM) and ECM/BCM values compared with healthy donors. Malnutrition was best reflected by the PhA values. Of the patients with SSc, 69 (55.7%) had malnutrition that was associated with severe disease and activity. As assessed by multivariate analysis, low predicted forced vital capacity and high N-terminal(NT)-proBNP values discriminated best between good and bad nutritional status. Among different clinical parameters, low PhA values were the best predictors for SSc-related mortality. BMI values were not related to disease symptoms or mortality. Fifty per cent of patients with SSc had a lower energy uptake related to their energy requirement, 19.8% related to their basal metabolism. Nutritional treatment improved the patients' nutritional status. In patients with SSc, malnutrition is common and not identified by BMI. BIA parameters reflect disease severity and provide best predictors for patient survival. Therefore, an assessment of nutritional status should be performed in patients with SSc.

  2. Physical Activity, Health Status and Risk of Hospitalization in Patients with Severe Chronic Obstructive Pulmonary Disease

    PubMed Central

    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

    Background 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. Objectives 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. Methods 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. Results 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). Conclusion 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. PMID:20234126

  3. 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

  4. 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

  5. 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.

  6. Side Effects of Long-Term Continuous Intra-arterial Nimodipine Infusion in Patients with Severe Refractory Cerebral Vasospasm after Subarachnoid Hemorrhage.

    PubMed

    Kieninger, Martin; Flessa, Julia; Lindenberg, Nicole; Bele, Sylvia; Redel, Andreas; Schneiker, André; Schuierer, Gerhard; Wendl, Christina; Graf, Bernhard; Silbereisen, Vera

    2017-07-06

    Long-term continuous intra-arterial nimodipine infusion (CIAN) is a rescue therapy option in cases of severe refractory cerebral vasospasm (CV) following acute non-traumatic subarachnoid hemorrhage (SAH). However, CIAN therapy can be associated with relevant side effects. Available studies focus on intracerebral complications, whereas extracerebral side effects are rarely examined. Aim of the present study was to generate descriptive data on the clinical course during CIAN therapy and expectable extracerebral side effects. All patients treated with CIAN therapy for at least 5 days between May 2011 and December 2015 were included. We retrospectively extracted data from the patient data management system regarding the period between 2 days before the beginning and 5 days after the termination of CIAN therapy to analyze the course of ventilation parameters and pulmonary gas exchange, hemodynamic support, renal and liver function, integrity of the gastrointestinal tract, and the occurrence of infectious complications. In addition, we recorded the mean daily values of intracranial pressure (ICP) and intracerebral problems associated with CIAN therapy. Data from 28 patients meeting inclusion criteria were analyzed. The mean duration of long-term CIAN therapy was 10.5 ± 4.5 days. Seventeen patients (60.7%) reached a good outcome level (Glasgow Outcome Scale [GOS] 4-5) 6 months after SAH. An impairment of the pulmonary gas exchange occurred only at the very beginning of CIAN therapy. The required vasopressor support with norepinephrine was significantly higher on all days during and the first day after CIAN therapy compared to the situation before starting CIAN therapy. Two patients required short-time resuscitation due to cardiac arrest during CIAN therapy. Acute kidney injury was observed in four patients, and one of them required renal replacement therapy with sustained low-efficiency daily dialysis. During CIAN therapy, 23 patients (82.1%) needed the escalation

  7. Ureteral Embolization to Prevent Thrombotic Obstruction of Nephrostomy Catheters in the Context of Refractory Hemorrhagic Radiation Cystitis with Severe Vesicoureteral Reflux

    PubMed Central

    Yarlagadda, Vidhush; Pettibon, Keith; Ertel, Nathan

    2016-01-01

    We present a case of refractory hemorrhagic radiation cystitis in a patient who failed conservative management and was unable to undergo operative urinary diversion secondary to multiple comorbidities. His management was complicated by recurrent obstruction of his nephrostomy catheters due to marked ureteral thrombus formation from blood refluxing into the ureters from the urinary bladder. We were successful in treating his condition by occluding his distal ureters with a combination of embolization coils and glue to prevent the reflux of blood in order to allow his nephrostomy catheters to function properly. PMID:27019759

  8. Ureteral Embolization to Prevent Thrombotic Obstruction of Nephrostomy Catheters in the Context of Refractory Hemorrhagic Radiation Cystitis with Severe Vesicoureteral Reflux.

    PubMed

    Yarlagadda, Vidhush; Pettibon, Keith; Ertel, Nathan; Nix, Jeffrey

    2016-01-01

    We present a case of refractory hemorrhagic radiation cystitis in a patient who failed conservative management and was unable to undergo operative urinary diversion secondary to multiple comorbidities. His management was complicated by recurrent obstruction of his nephrostomy catheters due to marked ureteral thrombus formation from blood refluxing into the ureters from the urinary bladder. We were successful in treating his condition by occluding his distal ureters with a combination of embolization coils and glue to prevent the reflux of blood in order to allow his nephrostomy catheters to function properly.

  9. Vitamin D and PTH status among adolescent and young females with severe dysmenorrhea.

    PubMed

    Abdul-Razzak, Khalid K; Obeidat, Bayan A; Al-Farras, Mudhaffar I; Dauod, Ali S

    2014-04-01

    To investigate Vitamin D and parathyroid hormone (PTH) status among adolescent and young females with severe and very severe dysmenorrhea. Cross-sectional study in specific selected sample. One Jordanian university. Fifty-six females, ages between 17 and 24 years, with severe and very severe dysmenorrhea were surveyed regarding demographics, pain with menstruation, and dietary intake of dairy products. Plasma Vitamin D, PTH levels were measured. About 61% of the studied population experience very severe dysmenorrhea. Half of participants had dairy intake less than 1 serving per day. The majority of participants (80%) had insufficient plasma vitamin D and 48% of them had hyperparathyroidism. A high prevalence of vitamin D insufficiency and secondary hyperparathyroidism and/or low dietary calcium intake among adolescent and young adult females who experience severe and very severe dysmenorrhea may negatively affect bone metabolism during achievement of peak bone mass at a young age and adverse bone health at older age. Copyright © 2014 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  10. 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

  11. 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

  12. 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.

  13. Association between Nutritional Status and Severity of Dengue Infection in Children in El Salvador

    PubMed Central

    Marón, Gabriela M.; Clará, A. Wilfrido; Diddle, John Wesley; Pleités, Ernesto B.; Miller, Laura; MacDonald, Gene; Adderson, Elisabeth E.

    2010-01-01

    Clinical observations and some studies suggest that dengue virus infection is more severe among children with better nutritional status. We examined the nutritional status of children in El Salvador and its relationship between this and the severity of dengue infection. Z-scores for weight-for-age, height-for-age, and body mass index (BMI)-for-age of children with dengue fever (66), dengue hemorrhagic fever (62), and healthy controls (74) were compared. There were no differences in weight-for-age or BMI-for-age Z-scores between the three groups. Children with dengue fever had a greater height-for-age than healthy controls but no significant differences in rates of stunting. There was no difference in height between children with dengue fever and dengue hemorrhagic fever. Excess nutrition does not appear to be a risk factor for severe forms of dengue infection in El Salvador, nor does malnutrition appear to be predictive of good outcomes. PMID:20134012

  14. Impact of chronic condition status and severity on dental utilization for Iowa Medicaid-enrolled children.

    PubMed

    Chi, Donald L; Momany, Elizabeth T; Neff, John; Jones, Michael P; Warren, John J; Slayton, Rebecca L; Weber-Gasparoni, Karin; Damiano, Peter C

    2011-02-01

    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. To assess the relationship between CC status and CC severity, respectively, on dental utilization for Iowa Medicaid-enrolled children. Retrospective cohort study of Iowa Medicaid data (January 1, 2003 to December 31, 2006). Medicaid-enrolled children aged 3 to 14 (N = 71,115) years. 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. 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). 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.

  15. Rural-urban differences in psychiatric status and functioning among clients with severe mental illness.

    PubMed

    Dottl, S L; Greenley, J R

    1997-08-01

    Studies of clients with severe mental illness (SMI) typically focus on individuals in larger urban areas. Less is known about clients in rural and smaller urban areas. Here we compare the psychiatric status, home and community activities of daily living, and social and vocational functioning of 1600 adult clients with SMI from 18 small-city and rural Wisconsin counties. Rural clients are less likely to have a diagnosis of schizophrenia or organic brain syndrome; have higher levels of general pathology, including more belligerent, bizarre, nervous, and depressive behaviors; and engage in fewer vocational activities than urban clients.

  16. 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

  17. The Association of Hepatitis C Serological Status with Several Risk Factors in Indonesia

    PubMed Central

    Pracoyo, Noer Endah; Suratri, Made Ayu Lely

    2016-01-01

    Hepatitis is an inflammation of the liver commonly caused by viral infection such as hepatitis A, B, C, D, and E but it is also possible by other causes. Infection with hepatitis C virus is also referred to as a disguise because the early infection is often asymptomatic that often goes undetected. This study aims at determining the several associated risk factors with hepatitis C serological status. The study design is cross-sectional. The biomedical data collection was carried out in 33 provinces in Indonesia with a population in urban blocks, census in Indonesia, where the sample is all household members over the age of one year from selected households by signing the informed consent. Total block census in selected urban area is about 971-block census with a total sample of 15.536 households. The results showed that there is a correlation between hepatitis C serological status and demographic group and that the age and occupation groups showed significant P value obtained at 0.001 (OR = 3.27, CI = 1.84–5.81) and 0.209 (OR = 0.23, CI = 0.59–0.94). In conclusion, there are risk factors such as age and occupation that have a correlation of being infected with hepatitis C serological status. PMID:27975082

  18. Spectral reflecting characteristics of dinas refractory

    SciTech Connect

    Zapechnikov, V.N.; Pushkin, V.T.; Zen'kovskii, A.G.

    1987-09-01

    This article outlines a nondestructive testing format which uses spectral reflectance to assess the remaining service life, the thermal degradation, and the insulating effectiveness of refractories used as insulating liners in glass melters. Thermal as well as mechanical influences on the reflectance behavior of several refractories are discussed.

  19. 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.

  20. Outcome of pulmonary rehabilitation in COPD patients with severely impaired health status

    PubMed Central

    van Ranst, Dirk; Otten, Henk; Meijer, Jan Willem; van ’t Hul, Alex J

    2011-01-01

    Introduction Effects of pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) patients with severely impaired health status are poorly documented since these patients are usually excluded from clinical trials. This retrospective, observational study aims to study the impact of disease on health status and the effects of PR on COPD patients referred to a tertiary center for PR in The Netherlands. Methods Between June 2006 and June 2010, 437 patients with COPD were allocated to our intensive, comprehensive PR program. Patients participated in this interdisciplinary program for 12 weeks for a weekly average of 20–25 hours. Before and directly after, several measures of physical performance and health-related quality of life were determined. Results At baseline, most patients (75%) had a Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage of III–IV. Peak exercise performance on a cycle ergometer was on average reduced to 43 ± 29 Watt, and health-related quality of life was significantly impaired, with a total score on the St George’s Respiratory Questionnaire (SGRQ) of 66. Health-care utilization in the year preceding PR was very high. After rehabilitation, all outcome measures improved statistically significantly (P < 0.001). Exercise performance measured with the 6 minute walking distance test improved clinically significantly in 68% of the patients, whereas 75% of the patients showed a clinically meaningful improvement in quality of life as measured with the SGRQ. Multiple regression analysis revealed that 19% of the variation in responses on the 6 minute walking distance test and the SGRQ could be explained on the basis of baseline characteristics. Conclusion The present study provides data to indicate that COPD patients may substantially benefit from rehabilitation in a tertiary pulmonary rehabilitation center, despite a severely impaired health status and high level of health-care utilization, in which prior

  1. Work status, daily activities and quality of life among people with severe mental illness.

    PubMed

    Eklund, Mona

    2009-03-01

    Work is often a desired goal for people with mental illness, as expressed by both themselves and their relatives. This study investigated the importance of work status, everyday activities and objective life indices for subjective quality of life, with a special focus on quality of life domains. The sample consisted of 103 individuals with severe mental illness in Sweden, a majority of whom had schizophrenia. Interview-based questionnaires were used to assess quality of life (MANSA) and activity factors (SDO, OVal-pd). Work status and activity in terms of actual doing were of some, but minor, importance to subjective quality of life domains, whereas satisfying and valuable activities were consistently associated with most quality of life domains. Although no causal relationship could be established, the findings indicate that open-market work might not be decisive for subjective quality of life, but that satisfying and meaningful everyday activities could contribute to a better life quality for those who have a severe and lasting mental illness.

  2. Reversal of Refractory Ulcerative Colitis and Severe Chronic Fatigue Syndrome Symptoms Arising from Immune Disturbance in an HLA-DR/DQ Genetically Susceptible Individual with Multiple Biotoxin Exposures.

    PubMed

    Gunn, Shelly R; Gunn, G Gibson; Mueller, Francis W

    2016-05-11

    Patients with multisymptom chronic conditions, such as refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS), present diagnostic and management challenges for clinicians, as well as the opportunity to recognize and treat emerging disease entities. In the current case we report reversal of co-existing RUC and CFS symptoms arising from biotoxin exposures in a genetically susceptible individual. A 25-year-old previously healthy male with new-onset refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS) tested negative for autoimmune disease biomarkers. However, urine mycotoxin panel testing was positive for trichothecene group and air filter testing from the patient's water-damaged rental house identified the toxic mold Stachybotrys chartarum. HLA-DR/DQ testing revealed a multisusceptible haplotype for development of chronic inflammation, and serum chronic inflammatory response syndrome (CIRS) biomarker testing was positive for highly elevated TGF-beta and a clinically undetectable level of vasoactive intestinal peptide (VIP). Following elimination of biotoxin exposures, VIP replacement therapy, dental extractions, and implementation of a mind body intervention-relaxation response (MBI-RR) program, the patient's symptoms resolved. He is off medications, back to work, and resuming normal exercise. This constellation of RUC and CFS symptoms in an HLA-DR/DQ genetically susceptible individual with biotoxin exposures is consistent with the recently described CIRS disease pathophysiology. Chronic immune disturbance (turbatio immuno) can be identified with clinically available CIRS biomarkers and may represent a treatable underlying disease etiology in a subset of genetically susceptible patients with RUC, CFS, and other immune disorders.

  3. Reversal of Refractory Ulcerative Colitis and Severe Chronic Fatigue Syndrome Symptoms Arising from Immune Disturbance in an HLADR/DQ Genetically Susceptible Individual with Multiple Biotoxin Exposures

    PubMed Central

    Gunn, Shelly R.; Gibson Gunn, G.; Mueller, Francis W.

    2016-01-01

    Patient: Male, 25 Final Diagnosis: Ulcerative colitis and chronic fatigue syndrome Symptoms: Colitis • profound fatigue • multi-joint pain • cognitive impairment • corneal keratitis Medication: — Clinical Procedure: VIP replacement therapy Specialty: Family Medicine Objective: Unusual clinical course Background: Patients with multisymptom chronic conditions, such as refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS), present diagnostic and management challenges for clinicians, as well as the opportunity to recognize and treat emerging disease entities. In the current case we report reversal of co-existing RUC and CFS symptoms arising from biotoxin exposures in a genetically susceptible individual. Case Report: A 25-year-old previously healthy male with new-onset refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS) tested negative for autoimmune disease biomarkers. However, urine mycotoxin panel testing was positive for trichothecene group and air filter testing from the patient’s water-damaged rental house identified the toxic mold Stachybotrys chartarum. HLA-DR/DQ testing revealed a multisusceptible haplotype for development of chronic inflammation, and serum chronic inflammatory response syndrome (CIRS) biomarker testing was positive for highly elevated TGF-beta and a clinically undetectable level of vasoactive intestinal peptide (VIP). Following elimination of biotoxin exposures, VIP replacement therapy, dental extractions, and implementation of a mind body intervention-relaxation response (MBI-RR) program, the patient’s symptoms resolved. He is off medications, back to work, and resuming normal exercise. Conclusions: This constellation of RUC and CFS symptoms in an HLA-DR/DQ genetically susceptible individual with biotoxin exposures is consistent with the recently described CIRS disease pathophysiology. Chronic immune disturbance (turbatio immuno) can be identified with clinically available CIRS biomarkers and

  4. The present status of xeroderma pigmentosum in Japan and a tentative severity classification scale.

    PubMed

    Nakano, Eiji; Masaki, Taro; Kanda, Fumio; Ono, Ryusuke; Takeuchi, Seiji; Moriwaki, Shinichi; Nishigori, Chikako

    2016-08-01

    Xeroderma pigmentosum (XP) is a rare autosomal recessive hereditary disease. Patients with XP have severe hypersensitivity to sunlight, resulting in skin cancers, and some patients have neurological symptoms. In Japan, XP complementation group A (XP-A) is the most common form, and it is associated with severe neurological symptoms. We performed a nationwide survey on XP to determine the present status of XP in Japan. The distribution of complementation groups in Japan was considerably different from that in other countries, but there was a higher frequency in group A and the variant type, which is similar to previous reports in Japan. Basal cell carcinoma was the most frequent skin cancer that patients with XP developed, followed by squamous cell carcinoma and malignant melanoma. The frequency of these skin cancers in patients with XP-A has decreased, and these skin cancers have been occurring in much older people than those previously observed. Diagnosing XP in patients at younger ages seems to encourage patients and their parents to use sun protection, which helps prevent skin cancer. We also created a tentative scale for classifying the severity of XP, and we evaluated the neurological symptoms of XP-A using this severity scale. Our classification correlated well with patients' age, suggesting that it may be useful and feasible in clinical practice to assess the progression of symptoms of each patient with XP and evaluate the effects of treatment in the future.

  5. Are there gender differences in wellbeing related to work status among persons with severe impairments?

    PubMed

    Reine, Ieva; Palmer, Edward; Sonnander, Karin

    2016-12-01

    The aim of this study was to analyse gender differences in wellbeing, as related to work status, among working-age people with severe impairments. This study is based on register and survey data for a sample of 7298 persons, drawn from the entire Swedish population of 15,515 working-age people 16-64 years old who, at the end of 2010, received Sweden's unique personal assistance allowance, an allowance paid from the Swedish Social Insurance Agency (SSIA) to persons with severe impairments, enabling them to pay for assistants to support them in the functions of daily life. Logistic regression models were used to estimate the strength of relations between six measures of wellbeing, work status (not working, irregular work and regular work) and gender, together with key confounders. Of the persons surveyed, 21% responded that they had regular work. Gender differences were found for all confounders, except for age. They were mostly in favour of men, which could reflect the general pattern in the labour market at large. Our results indicated there are substantial differences between non-working, irregularly working and working persons for several wellbeing aspects. This study analyses the contributions to wellbeing of work participation among working-age people with severe impairments, with a focus on gender differences. The analysis shows that work is an important determinant of the six measures of wellbeing examined, where the relationship between work participation and wellbeing is especially strong for peoples' perceived standard of living. This major finding holds for both genders; however, the data show gender imbalance, in that compared with women, there was a larger percentage of men with severe impairments who have regular work. Future research should focus on finer distinctions between the types of work and the value added of personal assistants in the work context. Measures of general health not available for this study are needed to filter out a clearer

  6. 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.

  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.

    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.

  9. Disease severity and treatment in adolescent idiopathic scoliosis: the impact of race and economic status.

    PubMed

    Zavatsky, Joseph M; Peters, Austin J; Nahvi, Farzon A; Bharucha, Neil J; Trobisch, Per D; Kean, Kristin E; Richard, Sandra; Bucello, Yolanda; Valdevit, Antonio; Lonner, Baron S

    2015-05-01

    Ethnic disparities have been documented in the incidence and treatment of many diseases. Additionally, race and socioeconomic status (SES) have been shown to affect disease severity and access to care in the recent orthopedic literature. To assess the role, if any, that race, SES, and health insurance type play in disease severity and treatment decisions in patients with adolescent idiopathic scoliosis. Retrospective chart review. Pediatric patients seen in a single surgeon's practice over 6 years (2004-2009). Treatment modality (observation, bracing, or surgery). Data were obtained from 403 patients seen over 6 years (2004-2009). A patient-reported questionnaire was used to collect race, age, family income, and parent marital status data. Race was self-reported as "Asian," "black or African American," "Hispanic or Latino," "white or Caucasian," or "Other." Socioeconomic status was determined using family income and type of health insurance as indicators. Major curve magnitude and prescribed initial treatment (observation, brace, or surgery) were assessed from physician records. An independent sample t test was used to detect differences in curve magnitude of the different racial groups. A Pearson chi-square analysis was used to detect group differences for curves in surgical patients, defined as curves greater than 40°, and their initial treatment. Patients self-identified with one of the following racial groups: white (N=219), black (N=86), Hispanic (N=44), Asian (N=37), or Other (N=17). Mean curve magnitude was greater in black than in white patients (33° vs. 28°, p<.05). Black patients were more likely to present with curves in the surgical range (34% vs. 24%, p<.05) and were more likely to have surgery as their initial treatment than white patients (34% vs. 19%, p<.05). Black patients had more limited health care plans and lower incomes compared with whites (p<.001). Patients with higher access insurance plans presented at a younger age than patients with

  10. Carotid atherosclerosis severity in relation to glycemic status: a cross-sectional population study.

    PubMed

    Mostaza, Jose M; Lahoz, Carlos; Salinero-Fort, Miguel A; de Burgos-Lunar, Carmen; Laguna, Fernando; Estirado, Eva; García-Iglesias, Francisca; González-Alegre, Teresa; Cornejo-Del-Río, Víctor; Sabín, Concesa; López, Silvia

    2015-10-01

    Intima-media thickness (IMT) is increased in subjects with prediabetes or newly diagnosed diabetes. However, no previous studies have evaluated the relationship between the severity of carotid atherosclerosis, assessed by the presence of carotid plaques or stenosis, and the glycemic status, assessed either by fasting glucose, an oral glucose tolerance test (OGTT) or A1C levels. Cross-sectional analysis of 1475 subjects (mean age 62 years, 44% males), randomly selected from the population. A fasting blood sample was obtained to determine glucose, lipids, and A1C levels. An OGTT was performed in non-diabetic subjects. Carotid atherosclerosis was evaluated by echo-doppler. A 10.5% of the population had a previous diagnosis of diabetes. Of the 1320 non-diabetic participants, 349 (26.4%) had normal fasting glucose, normal glucose tolerance and A1C < 5.7%, and were considered controls. Prediabetes was diagnosed in 850 subjects (64.4%), and diabetes was newly diagnosed in 121 (9.2%). The prevalence of patients with carotid plaques was 34.2% in controls, 45.1% in prediabetics, 64.2% in newly diagnosed diabetics, and 72.9% in established diabetic patients. These numbers were 0.3%, 1.1%, 5.0% and 7.7% for carotid stenosis, respectively. In multivariate analysis, glycemic status remained significantly associated with the prevalence of carotid plaques after adjusting for age, sex, statin treatment, and cardiovascular risk factors. Glycemic status is associated with all grades of carotid atherosclerosis, from early signs, as demonstrated by the IMT, to intermediate degrees, as demonstrated by the presence of carotid plaques, to advance atherosclerosis, as established by the presence of carotid stenosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Vitamin D Status in Different Stages of Disease Severity in Dogs with Chronic Valvular Heart Disease.

    PubMed

    Osuga, T; Nakamura, K; Morita, T; Lim, S Y; Nisa, K; Yokoyama, N; Sasaki, N; Morishita, K; Ohta, H; Takiguchi, M

    2015-01-01

    In humans with heart disease, vitamin D deficiency is associated with disease progression and a poor prognosis. A recent study showed that serum 25-hydroxyvitamin D [25(OH)D] concentration, the hallmark of vitamin D status, was lower in dogs with heart failure than in normal dogs, and a low concentration was associated with poor outcome in dogs with heart failure. To elucidate the vitamin D status of dogs with chronic valvular heart disease (CVHD) at different stages of disease severity. Forty-three client-owned dogs with CVHD. In this cross-sectional study, dogs were divided into 3 groups (14 dogs in Stage B1, 17 dogs in Stage B2, and 12 dogs in Stage C/D) according to ACVIM guidelines. Dogs underwent clinical examination including echocardiography. Serum 25(OH)D concentrations were measured in each dog. Serum 25(OH)D concentration was significantly lower in Stage B2 (median, 33.2 nmol/L; range, 4.9-171.7 nmol/L) and C/D (13.1 nmol/L; 4.9-58.1 nmol/L) than in Stage B1 (52.5 nmol/L; 33.5-178.0 nmol/L) and was not significantly different between Stage B2 and Stage C/D. Among clinical variables, there were significant negative correlations between 25(OH)D concentration and both left atrial-to-aortic root ratio and left ventricular end-diastolic diameter normalized for body weight. These results indicate that vitamin D status is associated with the degree of cardiac remodeling, and the serum 25(OH)D concentration begins to decrease before the onset of heart failure in dogs with CVHD. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  12. Corticosterone, inflammation, immune status and telomere length in frigatebird nestlings facing a severe herpesvirus infection

    PubMed Central

    Sebastiano, Manrico; Eens, Marcel; Angelier, Frederic; Pineau, Kévin; Chastel, Olivier; Costantini, David

    2017-01-01

    Herpesvirus outbreaks are common in natural animal populations, but little is known about factors that favour the infection and its consequences for the organism. In this study, we examined the pathophysiological consequences of a disease probably attributable to herpesvirus infection for several markers of immune function, corticosterone, telomere length and inflammation. In addition, we assessed whether any markers used in this study might be associated with the occurrence of visible clinical signs of the disease and its impact on short-term survival perspectives. To address our questions, in spring 2015, we collected blood samples from nestlings of the magnificent frigatebird (Fregata magnificens) that were free of any clinical signs or showed visible signs of the disease. We found that the plasma concentration of haptoglobin was strongly associated with the infection status and could predict probabilities of survival. We also found that nestlings with clinical signs had lower baseline corticosterone concentrations and similar telomere length compared with healthy nestlings, whereas we did not find any association of the infection status with innate immune defenses or with nitric oxide concentration. Overall, our results suggest that the plasma concentration of haptoglobin might be a valuable tool to assess survival probabilities of frigatebird nestlings facing a herpesvirus outbreak. PMID:28070333

  13. The influence of gender and hormone status on the severity and progression of keratoconus.

    PubMed

    Fink, Barbara A; Sinnott, Loraine T; Wagner, Heidi; Friedman, Chad; Zadnik, Karla

    2010-01-01

    To assess the effects of gender and hormone status on the severity and progression of keratoconus in patients enrolled in the Collaborative Longitudinal Evaluation of Keratoconus Study. The severity and progression of keratoconus in both men (M) and women were evaluated over a 4-year period that encompassed menopausal transition for hormone-active women (HA) and hormone-inactive women (HI). Four outcome measures were selected as indicators of the severity of keratoconus: high-contrast best-corrected visual acuity, low-contrast best-corrected visual acuity, the steep keratometric measurement, and corneal scarring (yes/no). There were no statistically significant differences among the 3 groups (M, HA, and HI) in race, history of atopic disease, family history of keratoconus, or rigid contact lens wear in the right and left eyes. At baseline, there were no significant differences among the 3 groups in high-contrast best-corrected visual acuity, low-contrast best-corrected visual acuity, or steep keratometric reading. Progression of keratoconus, as assessed by changes in these 3 continuous variables, was equal for the 3 groups. M had more corneal scarring than did HA or HI; however, there was no progression of scarring for any of the groups. Keratoconus progressed in both men and women, aged 48-59 years; however, there were no differences among the groups in progression.

  14. Haematological profile in leprosy. Part II--Relationship to severity of disease and treament status.

    PubMed

    Karat, A B; Rao, P S

    1978-01-01

    321 adult male lepromatous leprosy patients were studied for relationship between haematological findings, severity of disease and duration of treatment. Significant changes were noticed in relation in haemoglobin concentration, serum vitamin B12 and serum folate levels, serum albumin and globulin. No significant changes were observed in serum iron levels in relation to disease and treatment status. With rising bacterial load, there was a trend towards lower haemoglobin concentration, higher vitamin B12 level and lowered serum folate levels. Serum albumin showed a significant decline, while serum globulin showed a significant rise. The findings are discussed in relation to replacement of bone marrow by lepromatous tissue as well as possible interference in the metabolism of haematinics by M. leprae. The exact mechanism of neurlogical deficit in leprosy in relation to deficiency of vitamin B12 and folic acid need to be further elucidated.

  15. Discontinuing early prophylaxis in severe haemophilia leads to deterioration of joint status despite low bleeding rates.

    PubMed

    Nijdam, Annelies; Foppen, Wouter; De Kleijn, Piet; Mauser-Bunschoten, Evelien P; Roosendaal, Goris; van Galen, Karin P M; Schutgens, Roger E G; van der Schouw, Yvonne T; Fischer, Kathelijn

    2016-05-02

    Prophylaxis is the recommended treatment for children with severe haemophilia A, but whether prophylaxis should be continued in adulthood is still under debate. Previous studies with limited follow-up have suggested that some patients may be able to stop prophylaxis in adulthood, while maintaining good joint health. This single-centre observational cohort study examined patients with severe haemophilia A born 1970-1988 without inhibitor development, and assessed the long-term consequences of discontinuing prophylaxis. Patient-initiated changes in prophylaxis, including all switches to on-demand treatment lasting a minimum of two consecutive weeks, were recorded from the time self-infusion began until the last evaluation. Sixty-six patients were evaluated at a median age of 32.4 years: 26 % of patients had stopped prophylaxis for a median of 10 years, 15 % had interrupted prophylaxis and 59 % had continued prophylaxis. Annual joint bleeding rate (AJBR), Haemophilia Joint Health Score (HJHS-2.1; 0-124 points), radiological Pettersson score (0-78 points) and Haemophilia Activities List score (HAL; 100-0 points) were compared between patients who stopped and patients who continued prophylaxis. Although self-reported bleeding rates and functional limitations were similar in both groups (AJBR: 1.5 vs 1.2 and HAL: 84 vs 84 for those who stopped and continued prophylaxis, respectively), objective assessment of joint status showed increased arthropathy after 10 years of on-demand treatment in patients who stopped prophylaxis compared with those who continued (HJHS: 23 vs. 14 and Pettersson: 16 vs 5, respectively; P< 0.01). These results support continuation of long-term prophylaxis in adults and demonstrate the need for objective monitoring of joint status.

  16. Effects of HIV Infection on the Metabolic and Hormonal Status of Children with Severe Acute Malnutrition

    PubMed Central

    Hornik, Christoph P.; Kiyimba, Tonny; Bain, James; Muehlbauer, Michael; Kiboneka, Elizabeth; Stevens, Robert; St. Peter, John V.; Newgard, Christopher B.; Bartlett, John; Freemark, Michael

    2014-01-01

    Background HIV infection occurs in 30% of children with severe acute malnutrition in sub-Saharan Africa. Effects of HIV on the pathophysiology and recovery from malnutrition are poorly understood. Methods We conducted a prospective cohort study of 75 severely malnourished Ugandan children. HIV status/CD4 counts were assessed at baseline; auxologic data and blood samples were obtained at admission and after 14 days of inpatient treatment. We utilized metabolomic profiling to characterize effects of HIV infection on metabolic status and subsequent responses to nutritional therapy. Findings At admission, patients (mean age 16.3 mo) had growth failure (mean W/H z-score −4.27 in non-edematous patients) that improved with formula feeding (mean increase 1.00). 24% (18/75) were HIV-infected. Nine children died within the first 14 days of hospitalization; mortality was higher for HIV-infected patients (33% v. 5%, OR = 8.83). HIV-infected and HIV-negative children presented with elevated NEFA, ketones, and even-numbered acylcarnitines and reductions in albumin and amino acids. Leptin, adiponectin, insulin, and IGF-1 levels were low while growth hormone, cortisol, and ghrelin levels were high. At baseline, HIV-infected patients had higher triglycerides, ketones, and even-chain acylcarnitines and lower leptin and adiponectin levels than HIV-negative patients. Leptin levels rose in all patients following nutritional intervention, but adiponectin levels remained depressed in HIV-infected children. Baseline hypoleptinemia and hypoadiponectinemia were associated with increased mortality. Conclusions Our findings suggest a critical interplay between HIV infection and adipose tissue storage and function in the adaptation to malnutrition. Hypoleptinemia and hypoadiponectinemia may contribute to high mortality rates among malnourished, HIV-infected children. PMID:25050734

  17. Toxic Epidermal Necrolysis-like Reaction With Severe Satellite Cell Necrosis Associated With Nivolumab in a Patient With Ipilimumab Refractory Metastatic Melanoma.

    PubMed

    Nayar, Namrata; Briscoe, Karen; Fernandez Penas, Pablo

    2016-04-01

    Nivolumab is a fully humanized monoclonal antibody to PD-1, which has shown improved overall and progression-free survival. Across studies of nivolumab, grade 3 or 4 rash has been noted in <1% of patients. We present a case report of patient with metastatic melanoma treated with nivolumab through expanded access program, who developed toxic epidermal necrolysis. Ours is the first case report, reporting grade 4 skin toxicity associated with nivolumab. A 64-year-old female presented with widespread maculopapular skin rash with bullae and areas of skin detachment after receiving 2 doses of nivolumab for ipilimumab refractory metastatic melanoma (BRAF wild-type). She was initially treated with prednisone, which was soon changed to methyprednisone followed by immunoglobulin with minimal response to the rash. After discussion with Dermatology, she was given cyclosporine and high-dose prednisone with gradual but significant improvement in her rash. Her skin biopsy showed interface dermatitis with a lymphocytic infiltrate in the dermoepidermal junction and apoptotic keratinocytes with focal areas of complete necrosis of the epidermis with minimal infiltrate.

  18. Aquaporin 4 antibody [NMO Ab] status in patients with severe optic neuritis in India.

    PubMed

    Ambika, Selvakumar; Balasubramanian, Mahalakshmi; Theresa, Lily; Veeraputhiran, Akila; Arjundas, Deepak

    2015-12-01

    Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system that causes attacks of optic neuritis and transverse myelitis. The discovery of a specific serum marker for NMO-IgG antibody [aquaporin 4 antibody/AQP4 Ab] has revolutionised the treatment of demyelinating diseases. Severe vision loss can be seen in optic neuritis (ON) associated with both multiple sclerosis (MS) and NMO. Identifying this antibody in optic neuritis patients can help us to establish the likelihood of these patients developing NMO (Jarius et al. Neurol Sci 298:158-162, 2010). It is important to differentiate these two entities as the treatment strategies of MS and NMO are different. To the best of our knowledge, there is no published literature regarding the importance of identifying this antibody in severe optic neuritis in Indian patients. Hence we decided to screen our severe optic neuritis patients for this AQP4 Ab. To investigate the presence of aquaporin 4 antibody and determine its prognostic value for visual and neurological outcome, in patients with bilateral and recurrent [severe] ON without any previous neurological manifestations presenting to a neuro-ophthalmology clinic in India. Single centre, prospective study. 40 patients (27 female patients and 13 male) with severe optic neuritis [patients with no visual improvement by 4 weeks from onset of vision loss] who presented either as recurrent attacks or as bilateral and severe optic neuritis between January 2010 and June 2011 were enrolled. Clinical features, visual outcome and sequential neurological events were compared between the seropositive and the seronegative groups. Aquaporin 4 antibodies were detected from serum using ELISA technique and IIF technique. Presence of this antibody in the serum was considered to be seropositive status and patients who did not have this antibody were considered seronegatives. AQP4 antibodies were detected in 8 of the 40 patients with severe ON (20 %).The

  19. Biochemical markers of nutritional status and childhood malaria severity in Cameroon.

    PubMed

    Mfonkeu, Joël Bertrand Pankoui; Gouado, Inocent; Kuaté, Honoré Fotso; Zambou, Odile; Combes, Valéry; Grau, Georges Emile Raymond; Zollo, Paul Henri Amvam

    2010-09-01

    To investigate the part played by undernutrition in malaria severity, some biomarkers of nutritional status were assessed in children with severe malarial anaemia (MA) and cerebral malaria (CM) in comparison with healthy children or those with uncomplicated malaria. Undernutrition was assessed using the weight-for-age Z score (WAZ). Retinol was determined by HPLC; lipid profile, Ca, Mg and albumin were determined by spectrophotometry. Severe and moderate undernutritions were more prevalent in children with MA and those with the combined symptoms of CM and MA, but not in those with CM alone. Some perturbations were noticed in the lipid profile, but most of the values remained within the normal ranges. The risk of vitamin A deficiency, as assessed by plasma retinol concentration, was noteworthy in children with severe malaria: 0.48 × 10(-6) and 0.50 × 10(-6) mol/l, respectively, in children with MA and CM (reference value: >0.7 × 10(-6) mol/l). A significant difference was obtained for retinol values after an ANOVA of all the groups (P = 0.0029), with the value in the MA group being significantly low than that in the control group (P < 0.05); likewise, a significant difference was obtained after comparison of all the groups for Mg and albumin (P = 0.0064 and 0.0082, respectively). Despite their low number (n 6), fatal cases of CM had a normal mean WAZ on admission, but low values of retinol, albumin and HDL:LDL ratio. Despite these associations, undernutrition itself did not appear to be a primary factor associated with fatal outcome.

  20. Nutritional status and disease severity in patients with chronic obstructive pulmonary disease (COPD).

    PubMed

    Lee, Haejung; Kim, Sungmin; Lim, Yeonjung; Gwon, Hyejin; Kim, Yunseong; Ahn, Jong-Joon; Park, Hye-Kyung

    2013-01-01

    The purpose of this study was to identify the relationship between nutritional status and the severity of the disease in patients with COPD in South Korea. This study used pretest data from a larger intervention study. Data were collected from March to October 2010, and 251 patients diagnosed with COPD from five hospitals in South Korea were included in the analysis. All participants were interviewed face-to-face. Actual dietary intake was measured by a 24-h dietary recall, and the body mass index (BMI), obstruction of the airway (FEV1% predicted), degree of dyspnea (modified Medical Research Council: MMRC), and exercise capacity (6min walking distance: 6MWD) (BODE) index was calculated to estimate the severity of the condition. Lower BODE index scores indicate lower risk of mortality. The data were analyzed by descriptive statistics, a χ(2) test, t-tests, analysis of variance (ANOVA), Pearson correlation, and hierarchical multiple regression using SPSS 18.0. The mean age of the participants was 66.83 years and 92.4% of the participants were men. The mean total energy intake was 1431.65kcal, and the mean BODE index score was 2.89. Total energy intake significantly explained additional variance in BODE, BMI, the severity of the perceived dyspnea, and the length of 6min walk after controlling for age, duration after diagnosed with COPD, and physical activities. The findings of this study emphasized the importance of calorie intake in the disease severity among COPD patients. Further research on the effects of nutritional intervention on the health outcomes of patients with COPD is warranted. Copyright © 2013. Published by Elsevier Ireland Ltd.

  1. Depressive Symptoms, Cardiac Disease Severity, and Functional Status in Patients With Coronary Artery Disease (from the Heart and Soul Study).

    PubMed

    Schopfer, David W; Regan, Mathilda; Heidenreich, Paul A; Whooley, Mary A

    2016-11-01

    Patient-reported health status is highly valued as a key measure of health care quality, yet little is known about the extent to which it is determined by subjective perception compared with objective measures of disease severity. We sought to compare the associations of depressive symptoms and objective measures of cardiac disease severity with perceived functional status in patients with stable coronary artery disease. We assessed depressive symptoms, severity of cardiovascular disease, and perceived functional status in a cross-sectional study of 1,023 patients with stable coronary artery disease. We compared the extent to which patient-reported functional status was influenced by depressive symptoms versus objective measures of disease severity. We then evaluated perceived functional status as a predictor of subsequent cardiovascular hospitalizations during 8.8 years of follow-up. Patients with depressive symptoms were more likely to report poor functional status than those without depressive symptoms (44% vs 17%; p <0.001). After adjustment for traditional risk factors and co-morbid conditions, independent predictors of poor functional status were depressive symptoms (odds ratio [OR] 2.68, 95% confidence interval [CI] 1.89 to 3.79), poor exercise capacity (OR 2.30, 95% CI 1.65 to 3.19), and history of heart failure (OR 1.61, 95% CI 1.12 to 2.29). Compared with patients who had class I functional status, those with class II functional status had a 96% greater rate (hazard ratio 1.96, 95% CI 1.15 to 3.34) and those with class III or IV functional status had a 104% greater rate (hazard ratio 2.04, 95% CI 1.12 to 3.73) of hospitalization for HF, adjusted for baseline demographic characteristics, co-morbidities, cardiac disease severity, and depressive symptoms. In conclusion, depressive symptoms and cardiac disease severity were independently associated with patient-reported functional status. This suggests that perceived functional status may be as strongly

  2. Anti-interleukin-2 receptor monoclonal antibody (BT 563) in the treatment of severe acute GVHD refractory to systemic corticosteroid therapy.

    PubMed

    Cuthbert, R J; Phillips, G L; Barnett, M J; Nantel, S H; Reece, D E; Shepherd, J D; Klingemann, H G

    1992-11-01

    Fourteen patients with corticosteroid-resistant acute GVHD were treated with a murine monoclonal antibody to the pp55 interleukin-2 (IL-2) receptor (MoAb BT 563). Nine of the 14 patients had also failed Xoma-Zyme-H65 as GVHD prophylaxis and/or treatment. Seven patients had received HLA-matched sibling donor bone marrow transplants, five had received HLA-matched transplants from unrelated volunteer donors, and two had received one-antigen mismatched transplants from unrelated volunteer donors. At the time of MoAb BT 563 therapy, the overall clinical grading of acute GVHD (Seattle grading system) was as follows: grade II--one patient, grade III--four patients, and grade IV--nine patients. MoAb BT 563 was administered as a short iv infusion of 5 mg daily for 10 doses, followed by 5 mg on alternate days for a further five doses. A complete response (CR) was observed in four patients (28%), and a partial response (PR) in four patients (28%). All four complete responders were treated within 28 days of first onset of grade > or = II acute GVHD. Four patients (three CR, one PR) remain alive. One complete responder subsequently died from chronic GVHD. MoAb BT 563 administration was well tolerated in all 14 patients; no significant toxicity was observed. We conclude that MoAb BT 563 directed against the IL-2 receptor on activated T lymphocytes may be useful in treating corticosteroid-resistant acute GVHD if given early, but that it is of limited value in attempting to rescue patients with far-advanced refractory acute GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Comparisons of Subgingival Microbial Profiles of Refractory Periodontitis, Severe Periodontitis and Periodontal Health using the Human Oral Microbe Identification Microarray (HOMIM)

    PubMed Central

    Colombo, Ana Paula V.; Boches, Susan K.; Cotton, Sean L.; Goodson, J. Max; Kent, Ralph; Haffajee, Anne D.; Socransky, Sigmund S.; Hasturk, Hatice; Van Dyke, Thomas E.; Paster, Bruce J.

    2013-01-01

    Aim This study compared the subgingival microbiota of subjects with refractory periodontitis (RP) to those in subjects with treatable periodontitis (GR) or periodontal health (PH) using the Human Oral Microbe Identification Microarray (HOMIM). Methods At baseline, subgingival plaque samples were taken from 47 periodontitis and 20 PH individuals, and analyzed for the presence of 300 species by HOMIM. The periodontitis subjects were classified as RP (n=17) based on mean attachment loss (AL) and/or >3 sites with AL ≥2.5 mm after SRP, surgery and systemically administered amoxicillin and metronidazole or as GR (n=30) based on mean attachment gain and no sites with AL ≥2.5 mm after treatment. Significant differences in taxa among groups were sought using the Kruskal Wallis and Chi-square tests. Results More species were detected in diseased patients (GR or RP) than those without disease (PH). RP subjects were distinguished from GR and PH by a significantly high frequency of putative periodontal pathogens such as, Parvimonas micra, Campylobacter gracilis, Eubacterium nodatum, Selenomonas noxia, Tannerella forsythia, Porphyromonas gingivalis, Prevotella spp., Treponema spp., Eikenella corrodens, as well as “unusual” species (Pseudoramibacter alactolyticus, TM7 spp. oral taxon (OT) 346/356, Bacteroidetes spp. OT 272/274, Solobacterium moorei, Desulfobulbus sp. OT 041, Brevundimonas diminuta, Sphaerocytophaga sp. OT 337, Shuttleworthia satelles, Filifactor alocis, Dialister invisus/pneumosintes, Granulicatella adiacens, Mogibacterium tidmidum, Veillonella atypica, Mycoplasma salivarium, Synergistes sp. cluster II, Acidaminococcaceae [G-1] sp. OT 132/150/155/148/135) [p<0.05]. Species that were more prevalent in PH than in periodontitis patients included Actinomyces sp. OT 170, Actinomyces spp. cluster I, Capnocytophaga sputigena, Cardiobacterium hominis, Haemophilus parainfluenzae, Lautropia mirabilis, Propionibacterium propionicum, Rothia dentocariosa

  4. [Assessment of nutritional status and body composition in patients with COPD: comparison of several methods].

    PubMed

    Thibault, R; Le Gallic, E; Picard-Kossovsky, M; Darmaun, D; Chambellan, A

    2010-09-01

    In chronic obstructive pulmonary disease (COPD), loss of fat-free mass (FFM) reduces the prognosis. To assess their nutritional status and compare the relevance of several nutritional criteria, 47 COPD patients, already enrolled in our pulmonary rehabilitation programme, were evaluated. Assessment of nutritional status included anthropometry, serum albumin and transthyretin, bioimpedance analysis (BIA) and 3-day dietary record. The accuracy of these nutritional parameters was determined by comparison with FFM measured by BIA. The agreement between BIA and the 4-skinfold-thickness method was determined by statistical correlation and the Bland and Altman method. Energy intake, health care requirements and quality of life (QOL) score were compared with the FFM. According to the criteria used, the prevalence of undernutrition varied between 4 and 49%. In comparison with BIA, body mass index (BMI) below 20, triceps skinfold below the 5th percentile and transthyretin below 0.20 g/L had a specificity of around 100% for the diagnosis of undernutrition. There was a good agreement between BIA and the 4-skinfold-thickness method for the assessment of FFM (r=0.86, P<0.0001). Prior to any nutritional intervention, the patients with low FFM had higher protein-energy intake than patients with normal FFM. Low FFM was associated with a greater number of visits to the doctor, but had no impact on QOL. The assessment of FFM by BIA is the most sensitive method to detect undernutrition in COPD patients. Lowered values of BMI, triceps skinfold and transthyretin are predictive of loss of FFM. Copyright © 2010 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  5. Management of chronic refractory cough.

    PubMed

    Gibson, Peter G; Vertigan, Anne E

    2015-12-14

    Chronic refractory cough (CRC) is defined as a cough that persists despite guideline based treatment. It is seen in 20-46% of patients presenting to specialist cough clinics and it has a substantial impact on quality of life and healthcare utilization. Several terms have been used to describe this condition, including the recently introduced term cough hypersensitivity syndrome. Key symptoms include a dry irritated cough localized around the laryngeal region. Symptoms are not restricted to cough and can include globus, dyspnea, and dysphonia. Chronic refractory cough has factors in common with laryngeal hypersensitivity syndromes and chronic pain syndromes, and these similarities help to shed light on the pathophysiology of the condition. Its pathophysiology is complex and includes cough reflex sensitivity, central sensitization, peripheral sensitization, and paradoxical vocal fold movement. Chronic refractory cough often occurs after a viral infection. The diagnosis is made once the main diseases that cause chronic cough have been excluded (or treated) and cough remains refractory to medical treatment. Several treatments have been developed over the past decade. These include speech pathology interventions using techniques adapted from the treatment of hyperfunctional voice disorders, as well as the use of centrally acting neuromodulators such as gabapentin and pregabalin. Potential new treatments in development also show promise.

  6. Retrospective of the replantation of severed limbs in the People's Republic of China: current status and prospects.

    PubMed

    Zhang, Jian; Chen, Zhong Wei

    2002-01-01

    Thirty-eight years have past since Chinese surgeons first reported the successful replantation of a severed limb. The following article reports the current status of replantation surgery in the People's Republic of China, addresses issues of complex replantation and reconstruction of severed limbs, and discusses future prospects and implications for replantation microsurgery.

  7. Phase I Study of Quizartinib Administered Daily to Patients With Relapsed or Refractory Acute Myeloid Leukemia Irrespective of FMS-Like Tyrosine Kinase 3–Internal Tandem Duplication Status

    PubMed Central

    Cortes, Jorge E.; Kantarjian, Hagop; Foran, James M.; Ghirdaladze, Darejan; Zodelava, Mamia; Borthakur, Gautam; Gammon, Guy; Trone, Denise; Armstrong, Robert C.; James, Joyce; Levis, Mark

    2013-01-01

    Purpose FMS-like tyrosine kinase 3–internal tandem duplication (FLT3-ITD) mutations in acute myeloid leukemia (AML) are associated with early relapse and poor survival. Quizartinib potently and selectively inhibits FLT3 kinase activity in preclinical AML models. Patients and Methods Quizartinib was administered orally at escalating doses of 12 to 450 mg/day to 76 patients (median age, 60 years; range, 23 to 86 years; with a median of three prior therapies [range, 0 to 12 therapies]), enrolled irrespective of FLT3-ITD mutation status in a phase I, first-in-human study in relapsed or refractory AML. Results Responses occurred in 23 (30%) of 76 patients, including 10 (13%) complete remissions (CR) of any type (two CRs, three CRs with incomplete platelet recovery [CRp], five CRs with incomplete hematologic recovery [CRi]) and 13 (17%) with partial remissions (PRs). Of 17 FLT3-ITD–positive patients, nine responded (53%; one CR, one CRp, two CRis, five PRs); of 37 FLT3-ITD–negative patients, five responded (14%; two CRps, three PRs); of 22 with FLT3-ITD–indeterminate/not tested status, nine responded (41%; one CR, three CRis, five PRs). Median duration of response was 13.3 weeks; median survival was 14.0 weeks. The most common drug-related adverse events (> 10% incidence) were nausea (16%), prolonged QT interval (12%), vomiting (11%), and dysgeusia (11%); most were ≤ grade 2. The maximum-tolerated dose was 200 mg/day, and the dose-limiting toxicity was grade 3 QT prolongation. FLT3-ITD phosphorylation was completely inhibited in an in vitro plasma inhibitory assay. Conclusion Quizartinib has clinical activity in patients with relapsed/refractory AML, particularly those with FLT3-ITD, and is associated with an acceptable toxicity profile. PMID:24002496

  8. 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.

  9. CFB refractory maintenance

    SciTech Connect

    Johnson, R.C.

    1994-12-31

    The CFB maintenance manager has to make rapid-fire decisions regarding refractory maintenance during short or unscheduled turnarounds. This presentation offers a hands-on approach to expedient refractory failure analyses with specific repair recommendations. Photographs of most typical CFB refractory failures and their structural repairs are discussed. The most reliable repairs can be expected by using the latest state-of-the-art refractory materials and installation techniques. Refractory materials are consumable; therefore minor repairs should always be conducted at the first opportunity; this will preclude future major repairs. During a short or unscheduled outage, major repairs should be confined to the specific structural repair site; the removal of good, serviceable refractory is unnecessary under these conditions.

  10. 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

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

    PubMed Central

    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

  12. Effectiveness of rotavirus vaccine in preventing severe gastroenteritis in young children according to socioeconomic status.

    PubMed

    Gosselin, Virginie; Généreux, Mélissa; Gagneur, Arnaud; Petit, Geneviève

    2016-10-02

    In 2011, the monovalent rotavirus vaccine was introduced into a universal immunization program in Quebec (Canada). This retrospective cohort study assessed vaccine effectiveness (VE) in preventing acute gastroenteritis (AGE) and rotavirus gastroenteritis (RVGE) hospitalizations among children <3 y living in the Quebec Eastern Townships region according to socioeconomic status (SES). Data were gathered from a tertiary hospital database paired with a regional immunization registry. Three cohorts of children were followed: (1) vaccinated children born in post-universal vaccination period (2011-2013, n = 5,033), (2) unvaccinated children born in post-universal vaccination period (n = 1,239), and (3) unvaccinated children born in pre-universal vaccination period (2008-2010, n = 6,436). In each cohort, AGE and RVGE hospitalizations were identified during equivalent follow-up periods to calculate VE globally and according to neighborhood-level SES. Using multivariable logistic regression, adjusted odds ratios (OR) were computed to obtain VE (1-OR). Adjusted VE of 2 doses was 62% (95% confidence interval [CI]: 37%-77%) and 94% (95%CI: 52%-99%) in preventing AGE and RVGE hospitalization, respectively. Stratified analyses according to SES showed that children living in neighborhoods with higher rates of low-income families had significantly lower VE against AGE hospitalizations compared to neighborhoods with lower rates of low-income families (30% vs. 78%, p = 0.027). Our results suggest that the rotavirus vaccine is highly effective in preventing severe gastroenteritis in young children, particularly among the most well-off. SES seems to influence rotavirus VE, even in a high-income country like Canada. Further studies are needed to determine factors related to lower rotavirus VE among socioeconomically disadvantaged groups.

  13. Effectiveness of rotavirus vaccine in preventing severe gastroenteritis in young children according to socioeconomic status

    PubMed Central

    Gosselin, Virginie; Généreux, Mélissa; Gagneur, Arnaud; Petit, Geneviève

    2016-01-01

    ABSTRACT In 2011, the monovalent rotavirus vaccine was introduced into a universal immunization program in Quebec (Canada). This retrospective cohort study assessed vaccine effectiveness (VE) in preventing acute gastroenteritis (AGE) and rotavirus gastroenteritis (RVGE) hospitalizations among children <3 y living in the Quebec Eastern Townships region according to socioeconomic status (SES). Data were gathered from a tertiary hospital database paired with a regional immunization registry. Three cohorts of children were followed: (1) vaccinated children born in post-universal vaccination period (2011–2013, n = 5,033), (2) unvaccinated children born in post-universal vaccination period (n = 1,239), and (3) unvaccinated children born in pre-universal vaccination period (2008–2010, n = 6,436). In each cohort, AGE and RVGE hospitalizations were identified during equivalent follow-up periods to calculate VE globally and according to neighborhood-level SES. Using multivariable logistic regression, adjusted odds ratios (OR) were computed to obtain VE (1-OR). Adjusted VE of 2 doses was 62% (95% confidence interval [CI]: 37%–77%) and 94% (95%CI: 52%–99%) in preventing AGE and RVGE hospitalization, respectively. Stratified analyses according to SES showed that children living in neighborhoods with higher rates of low-income families had significantly lower VE against AGE hospitalizations compared to neighborhoods with lower rates of low-income families (30% vs. 78%, p = 0.027). Our results suggest that the rotavirus vaccine is highly effective in preventing severe gastroenteritis in young children, particularly among the most well-off. SES seems to influence rotavirus VE, even in a high-income country like Canada. Further studies are needed to determine factors related to lower rotavirus VE among socioeconomically disadvantaged groups. PMID:27367155

  14. Profile of Medical Charges for Children by Health Status Group and Severity Level in a Washington State Health Plan

    PubMed Central

    Neff, John M; Sharp, Virginia L; Muldoon, John; Graham, Jeff; Myers, Kristin

    2004-01-01

    Objective To identify children and evaluate patterns of charges for pediatric medical care, by overall health status, severity of illness, and categories of medical service. Data Sources Enrollment, claims, and charges data from a Washington State health plan. The study population includes all children ages 0 to 18 years during calendar year 1999. Study Design Children were classified into clinically defined health status groups and severity levels using Clinical Risk Groups (CRGs). Health plan charges were analyzed according to core health status group, severity level, and category of service. Data Collection The three secondary data sources were obtained electronically from the health plan and cleaned for unique members and data quality before analysis. Principal Findings Children classified as healthy (85.2 percent) had mean and median annual charges of $485 and $191. Children with one or more chronic conditions (9.5 percent) had mean and median charges increasing by status and severity group from $2,303 to $76,143 and from $1,151 to $19,456, and accounted for 45.2 percent of all charges. Distribution of charges varied across health status groups. Healthy children had 70.6 percent of their charges in outpatient and physician services. Children classified in the complex, catastrophic, and malignancy groups had 67 percent of their charges in inpatient encounters. Children with chronic conditions accounted for 31.8 percent of all physician, 41.8 percent of outpatient, 47.7 percent of pharmacy, 60.7 percent of inpatient, and 75.8 percent of all other charges. Conclusions Children with chronic conditions account for a disproportionately high percentage of children's health expenditures. They account for different percentages of expenses for different medical services. These percentages vary according to health status and severity. This analysis can be used to identify and track groups of children for various purposes. PMID:14965078

  15. 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.

  16. 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.

  17. [Effects of different intakes of protein on nutritional status in severe stroke patients].

    PubMed

    Zhang, Li; Li, Zebin; Luo, Bin; Li, Zengning; Lei Min; Jing, Yongmin

    2014-11-01

    statistically significant on the 14th day post-intervention compared with pre-intervention and on the 7th day post-intervention. The differences of TP, ALB and Hb among the three groups were statistically significant on the 14th day post-intervention. (3) Cr in the three groups did not have significant differences during the observation period. BUN of group A and group B were both increased post-interventinon, the differences were statistically significant compared with pre-intervention and there were statistically significant differences between group A and group B (P < 0.05). BUN in group C did not have significant changes during the observation period. On the 14th day post-intervention, the differences of BUN were statistically significant among the three groups (P < 0.05). The nutritional effect of protein intake at 1.6 g/kg is better than 0.9 g/kg and 1.2 g/kg on improving the nutritional status in severe stroke patients.

  18. Development of improved refractories

    SciTech Connect

    Wereszczak, A.A.; Ferber, M.K.; Liu, K.C.; Moore, R.E.

    1997-04-01

    The goal of the proposed project is to provide expertise and facilities for the high temperature mechanical properties characterization of refractory materials which are of interest to the US DOE`s Office of Industrial Technologies Advanced Industrial Materials Project. Initially the project would establish dedicated refractory testing facilities which would be capable of generating representative engineering creep and high temperature modulus of elasticity (MOE) data to a temperature of 3300{degrees}F (1815{degrees}C) in ambient air. The generated engineering creep and MOE data would serve R&D requirements of refractories-manufacturers and its glass-manufacturer end-users and designers. The relevance of this effort to the refractory and glass-making industries would be ensured by coordinating the research activities through a membership with Alfred University`s Center for Glass Research (CGR) Satellite Center at the University of Missouri-Rolla (UMR), an NSF Center. Valid engineering creep and high temperature MOE data currently do not exist for almost all commercial refractories. Refractory end-users such as glass-manufacturers require such data for efficient and economical design of their various glass-melting furnace superstructures (e.g., furnace crowns). Refractories in glass production furnaces may be subjected to extreme temperatures as high as 3200{degrees}F (1760{degrees}C). With the simultaneous imposition of mechanical and thermal stresses, creep deformation of the refractory material will assuredly occur as a consequence. Designers must ensure that the structural integrity is maintained, so these high temperature deformations must be considered for successful glass furnace superstructure design. These criteria can only be satisfied with the utilization of representative engineering creep and high temperature MOE data for the refractory materials that are chosen for the design of the refractory superstructures.

  19. Parent and Teacher Assessments of the Developmental Status of Children with Severe, Mild/Moderate, or No Developmental Disabilities.

    ERIC Educational Resources Information Center

    Hundert, Joel; Morrison, Laura; Mahoney, William; Mundy, Faith; Vernon, Mary Lou

    1997-01-01

    Teachers and parents rated the developmental status of 225 preschool children with and without disabilities on the Vineland Adaptive Behavior Scale. The study found a significant correlation between teacher and parent ratings for children with severe disabilities but not for children with mild/moderate or no disabilities. (DB)

  20. 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

  1. Nasogastric tube-administered alectinib achieved long-term survival in a crizotinib-refractory nonsmall cell lung cancer patient with a poor performance status.

    PubMed

    Kanai, Osamu; Kim, Young Hak; Nakatani, Koichi; Fujita, Kohei; Mio, Tadashi

    2017-06-01

    Alectinib shows remarkable efficacy against anaplastic lymphoma kinase (ALK)-positive nonsmall cell lung cancer (NSCLC), with minimal adverse effects. Therefore, alectinib may provide a survival benefit to ALK-positive NSCLC patients with a poor performance status. If the medication cannot be taken by mouth, the patient may be given alectinib through a nasogastric tube.

  2. Perspectives of Japanese mothers with severe mental illness regarding the disclosure of their mental health status to their children.

    PubMed

    Ueno, Rie; Kamibeppu, Kiyoko

    2012-10-01

    This study examined Japanese mothers with severe mental illness and their perspectives about disclosing their mental health status to their children. Seventy-four outpatients diagnosed with schizophrenia or mood disorders were recruited. We utilized a cross-sectional design and a self-report questionnaire. Approximately 72% of the participants disclosed their mental health status to their children. The reasons for disclosure and nondisclosure varied. Our findings indicate that although both the disclosing and nondisclosing groups held beliefs about disclosure, many mothers appeared to struggle with these issues. It is essential that clinicians are aware of this issue so they may appropriately help the mothers.

  3. Current Status and Trends in Timber Severence Tax Legislation in the South

    Treesearch

    Terry K. Haines

    1995-01-01

    Severance tax programs currently exist in eight States in the South. These laws have been enacted primarily to encourage better forest management and to provide revenues for a variety of forestry initiatives. In most States, either the severer or the primary processor of forest products is designated as the taxpayer. Severance tax rates are established as either: (1) a...

  4. BALB/c Mice Infected with Antimony Treatment Refractory Isolate of Leishmania braziliensis Present Severe Lesions due to IL-4 Production

    PubMed Central

    Costa, Diego L.; Carregaro, Vanessa; Lima-Júnior, Djalma S.; Silva, Neide M.; Milanezi, Cristiane M.; Cardoso, Cristina R.; Giudice, Ângela; de Jesus, Amélia R.; Carvalho, Edgar M.; Almeida, Roque P.; Silva, João S.

    2011-01-01

    Background Leishmania braziliensis is the main causative agent of cutaneous leishmaniasis in Brazil. Protection against infection is related to development of Th1 responses, but the mechanisms that mediate susceptibility are still poorly understood. Murine models have been the most important tools in understanding the immunopathogenesis of L. major infection and have shown that Th2 responses favor parasite survival. In contrast, L. braziliensis–infected mice develop strong Th1 responses and easily resolve the infection, thus making the study of factors affecting susceptibility to this parasite difficult. Methodology/Principal Findings Here, we describe an experimental model for the evaluation of the mechanisms mediating susceptibility to L. braziliensis infection. BALB/c mice were inoculated with stationary phase promastigotes of L. braziliensis, isolates LTCP393(R) and LTCP15171(S), which are resistant and susceptible to antimony and nitric oxide (NO), respectively. Mice inoculated with LTCP393(R) presented larger lesions that healed more slowly and contained higher parasite loads than lesions caused by LTCP15171(S). Inflammatory infiltrates in the lesions and production of IFN-γ, TNF-α, IL-10 and TGF-β were similar in mice inoculated with either isolate, indicating that these factors did not contribute to the different disease manifestations observed. In contrast, IL-4 production was strongly increased in LTCP393(R)-inoculated animals and also arginase I (Arg I) expression. Moreover, anti-IL-4 monoclonal antibody (mAb) treatment resulted in decreased lesion thickness and parasite burden in animals inoculated with LTCP393(R), but not in those inoculated with LTCP15171(S). Conclusion/Significance We conclude that the ability of L. braziliensis isolates to induce Th2 responses affects the susceptibility to infection with these isolates and contributes to the increased virulence and severity of disease associated with them. Since these data reflect what happens

  5. Advances in nondestructive evaluation methods for inspection of refractory concretes

    SciTech Connect

    Ellingson, W. A.

    1980-01-01

    Refractory concrete linings are essential to protect steel pressure boundaries from high-temperature agressive erosive/corrosive environments. Castable refractory concretes have been gaining more acceptance as information about their performance increases. Economic factors, however, have begun to impose high demands on the reliability of refractory materials. Advanced nondestructive evaluation methods are being developed to assist the refractory user. Radiographic techniques, thermography, acoustic-emission detection, and interferometry have been shown to yield information on the structural status of refractory concrete. Methods using /sup 60/Co radiation sources are capable of yielding measurements of refractory wear rate as well as images of cracks and/or voids in pre- and post-fired refractory linings up to 60 cm thick. Thermographic (infrared) images serve as a qualitative indicator of refractory spalling, but quantitative measurements are difficult to obtain from surface-temperature mapping. Acoustic emission has been shown to be a qualitative indicator of thermomechanical degradation of thick panels of 50 and 95% Al/sub 2/O/sub 3/ during initial heating and cooling at rates of 100 to 220/sup 0/C/h. Laser interferometry methods have been shown to be capable of complete mappings of refractory lining thicknesses. This paper will present results obtained from laboratory and field applications of these methods in petrochemical, steel, and coal-conversion plants.

  6. 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.

  7. Nitroso-redox status and vascular function in marginal and severe ascorbate deficiency.

    PubMed

    Garcia-Saura, Maria-Francisca; Saijo, Fumito; Bryan, Nathan S; Bauer, Selena; Rodriguez, Juan; Feelisch, Martin

    2012-10-01

    Marginal vitamin C (ascorbic acid) deficiency is a prevalent yet underappreciated risk factor for cardiovascular disease. Along with glutathione, ascorbate plays important roles in antioxidant defense and redox signaling. Production of nitric oxide (NO) and reactive oxygen species and their interaction, giving rise to nitroso and nitrosyl product formation, are key components of the redox regulation/signaling network. Numerous in vitro studies have demonstrated that these systems are interconnected via multiple chemical transformation reactions, but little is known about their dynamics and significance in vivo. We sought to investigate the time-course of changes in NO/redox status and vascular function during ascorbate depletion in rats unable to synthesize vitamin C. We here show that both redox and protein nitros(yl)ation status in blood and vital organs vary dynamically during development of ascorbate deficiency. Prolonged marginal ascorbate deficiency is associated with cell/tissue-specific perturbations in ascorbate and glutathione redox and NO status. Scurvy develops earlier in marginally deficient compared to adequately supplemented animals, with blunted compensatory NO production and a dissociation of biochemistry from clinical symptomology in the former. Paradoxically, aortic endothelial reactivity is enhanced rather than impaired, irrespective of ascorbate status. Innovation/Conclusion: Enhanced NO production and protein nitros(yl)ation are integral responses to the redox stress of acute ascorbate deprivation. The elevated cardiovascular risk in marginal ascorbate deficiency is likely to be associated with perturbations of NO/redox-sensitive signaling nodes unrelated to the regulation of vascular tone. This new model may have merit for the future study of redox-sensitive events in marginal ascorbate deficiency.

  8. Nitroso-Redox Status and Vascular Function in Marginal and Severe Ascorbate Deficiency

    PubMed Central

    Garcia-Saura, Maria-Francisca; Saijo, Fumito; Bryan, Nathan S.; Bauer, Selena; Rodriguez, Juan

    2012-01-01

    Abstract Marginal vitamin C (ascorbic acid) deficiency is a prevalent yet underappreciated risk factor for cardiovascular disease. Along with glutathione, ascorbate plays important roles in antioxidant defense and redox signaling. Production of nitric oxide (NO) and reactive oxygen species and their interaction, giving rise to nitroso and nitrosyl product formation, are key components of the redox regulation/signaling network. Numerous in vitro studies have demonstrated that these systems are interconnected via multiple chemical transformation reactions, but little is known about their dynamics and significance in vivo. Aims: We sought to investigate the time-course of changes in NO/redox status and vascular function during ascorbate depletion in rats unable to synthesize vitamin C. Results: We here show that both redox and protein nitros(yl)ation status in blood and vital organs vary dynamically during development of ascorbate deficiency. Prolonged marginal ascorbate deficiency is associated with cell/tissue-specific perturbations in ascorbate and glutathione redox and NO status. Scurvy develops earlier in marginally deficient compared to adequately supplemented animals, with blunted compensatory NO production and a dissociation of biochemistry from clinical symptomology in the former. Paradoxically, aortic endothelial reactivity is enhanced rather than impaired, irrespective of ascorbate status. Innovation/Conclusion: Enhanced NO production and protein nitros(yl)ation are integral responses to the redox stress of acute ascorbate deprivation. The elevated cardiovascular risk in marginal ascorbate deficiency is likely to be associated with perturbations of NO/redox-sensitive signaling nodes unrelated to the regulation of vascular tone. This new model may have merit for the future study of redox-sensitive events in marginal ascorbate deficiency. Antioxid. Redox Signal. 17, 937–950. PMID:22304648

  9. Severe depression as the sole symptom of affective focal status epilepticus

    PubMed Central

    Dimitriadis, Konstantinos; Pfefferkorn, Thomas; Noachtar, Soheyl

    2014-01-01

    Depression as well as fear, joy and anger have been described as the semiological features of focal epileptic seizures. When emotions present as the sole symptoms of epileptic seizures, they may easily be misdiagnosed as a psychiatric disorder. We describe a patient with affective focal status epilepticus, secondary to limbic encephalitis, in which depression was the only clinical manifestation. Through EEG correlates the epileptic nature of depression could be proven. Furthermore, we discuss the association between epilepsy and depression, as well as the link between ictal depression and suicidal rates. PMID:24827645

  10. Relationship between energy expenditure, nutritional status and clinical severity before starting enteral nutrition in critically ill children.

    PubMed

    Botrán, Marta; López-Herce, Jesús; Mencía, Santiago; Urbano, Javier; Solana, Maria José; García, Ana; Carrillo, Angel

    2011-03-01

    The objective of the present study was to investigate the relationship between energy expenditure (EE), biochemical and anthropometric nutritional status and severity scales in critically ill children. We performed a prospective observational study in forty-six critically ill children. The following variables were recorded before starting nutrition: age, sex, diagnosis, weight, height, risk of mortality according to the Paediatric Risk Score of Mortality (PRISM), the Revised Paediatric Index of Mortality (PIM2) and the Paediatric Logistic Organ Dysfunction (PELOD) scales, laboratory parameters (albumin, total proteins, prealbumin, transferrin, retinol-binding protein, cholesterol and TAG, and nitrogen balance) and EE measured by indirect calorimetry. The results showed that there was no relationship between EE and clinical severity evaluated using the PRISM, PIM2 and PELOD scales or with the anthropometric nutritional status or biochemical alterations. Finally, it was concluded that neither nutritional status nor clinical severity is related to EE. Therefore, EE must be measured individually in each critically ill child using indirect calorimetry.

  11. Mesenchymal stromal cells from pooled mononuclear cells of multiple bone marrow donors as rescue therapy in pediatric severe steroid-refractory graft-versus-host disease: a multicenter survey

    PubMed Central

    Kuçi, Zyrafete; Bönig, Halvard; Kreyenberg, Hermann; Bunos, Milica; Jauch, Anna; Janssen, Johannes W.G.; Škifić, Marijana; Michel, Kristina; Eising, Ben; Lucchini, Giovanna; Bakhtiar, Shahrzad; Greil, Johann; Lang, Peter; Basu, Oliver; von Luettichau, Irene; Schulz, Ansgar; Sykora, Karl-Walter; Jarisch, Andrea; Soerensen, Jan; Salzmann-Manrique, Emilia; Seifried, Erhard; Klingebiel, Thomas; Bader, Peter; Kuçi, Selim

    2016-01-01

    To circumvent donor-to-donor heterogeneity which may lead to inconsistent results after treatment of acute graft-versus-host disease with mesenchymal stromal cells generated from single donors we developed a novel approach by generating these cells from pooled bone marrow mononuclear cells of 8 healthy “3rd-party” donors. Generated cells were frozen in 209 vials and designated as mesenchymal stromal cell bank. These vials served as a source for generation of clinical grade mesenchymal stromal cell end-products, which exhibited typical mesenchymal stromal cell phenotype, trilineage differentiation potential and at later passages expressed replicative senescence-related markers (p21 and p16). Genetic analysis demonstrated their genomic stability (normal karyotype and a diploid pattern). Importantly, clinical end-products exerted a significantly higher allosuppressive potential than the mean allosuppressive potential of mesenchymal stromal cells generated from the same donors individually. Administration of 81 mesenchymal stromal cell end-products to 26 patients with severe steroid-resistant acute graft-versus-host disease in 7 stem cell transplant centers who were refractory to many lines of treatment, induced a 77% overall response at the primary end point (day 28). Remarkably, although the cohort of patients was highly challenging (96% grade III/IV and only 4% grade II graft-versus-host disease), after treatment with mesenchymal stromal cell end-products the overall survival rate at two years follow up was 71±11% for the entire patient cohort, compared to 51.4±9.0% in graft-versus-host disease clinical studies, in which mesenchymal stromal cells were derived from single donors. Mesenchymal stromal cell end-products may, therefore, provide a novel therapeutic tool for the effective treatment of severe acute graft-versus-host disease. PMID:27175026

  12. Lipid peroxidation and antioxidant status in vagina microenvironment of patients with several common vaginitis.

    PubMed

    Guo, H Y; Hu, X M; Han, D D; Wang, Z P; Meng, L

    2013-01-01

    Oxidative stress has been suggested to play an important role in many diseases, including vaginitis. To evaluate oxidative biomarkers in the secretion of cervix samples of vaginitis, this study will illustrate the status of lipid peroxidation and antioxidant status in vaginal microenvironment. A total of 257 patients with vaginitis, including candida vaginitis, bacterial vaginosis, and trichomonas vaginitis were involved in this study. Cervico-vaginal fluid was collected from these patients before and after treatment, and the malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), hydrogen peroxide (H2O2), and vitamin C levels were measured by enzyme-linked immunosorbent assay (ELISA). The results revealed that the MDA and H2O2 levels were increased in the vaginitis patients, while there was no significant difference in MDA level among different kinds of vaginitis before treatment. The CAT and vitamin C levels in vaginitis were decreased before treatment. Moreover, the data also showed that the MDA and H2O2 levels were decreased, while the CAT, SOD, and vitamin C levels were increased after received treatment, respectively, and there was no significant difference between controls and vaginitis. This study indicated that oxidative stress played an important role in vaginitis.

  13. Refractory alloy technology for space nuclear power applications

    SciTech Connect

    Cooper, R.H. Jr.; Hoffman, E.E.

    1984-01-01

    Purpose of this symposium is twofold: (1) to review and document the status of refractory alloy technology for structural and fuel-cladding applications in space nuclear power systems, and (2) to identify and document the refractory alloy research and development needs for the SP-100 Program in both the short and the long term. In this symposium, an effort was made to recapture the space reactor refractory alloy technology that was cut off in midstream around 1973 when the national space nuclear reactor program began in the early 1960s, was terminated. The six technical areas covered in the program are compatibility, processing and production, welding and component fabrication, mechanical and physical properties, effects of irradiation, and machinability. The refractory alloys considered are niobium, molybdenum, tantalum, and tungsten. Thirteen of the 14 pages have been abstracted separately. The remaining paper summarizes key needs for further R and D on refractory alloys. (DLC)

  14. Iron refractory iron deficiency anemia

    PubMed Central

    De Falco, Luigia; Sanchez, Mayka; Silvestri, Laura; Kannengiesser, Caroline; Muckenthaler, Martina U.; Iolascon, Achille; Gouya, Laurent; Camaschella, Clara; Beaumont, Carole

    2013-01-01

    Iron refractory iron deficiency anemia is a hereditary recessive anemia due to a defect in the TMPRSS6 gene encoding Matriptase-2. This protein is a transmembrane serine protease that plays an essential role in down-regulating hepcidin, the key regulator of iron homeostasis. Hallmarks of this disease are microcytic hypochromic anemia, low transferrin saturation and normal/high serum hepcidin values. The anemia appears in the post-natal period, although in some cases it is only diagnosed in adulthood. The disease is refractory to oral iron treatment but shows a slow response to intravenous iron injections and partial correction of the anemia. To date, 40 different Matriptase-2 mutations have been reported, affecting all the functional domains of the large ectodomain of the protein. In vitro experiments on transfected cells suggest that Matriptase-2 cleaves Hemojuvelin, a major regulator of hepcidin expression and that this function is altered in this genetic form of anemia. In contrast to the low/undetectable hepcidin levels observed in acquired iron deficiency, in patients with Matriptase-2 deficiency, serum hepcidin is inappropriately high for the low iron status and accounts for the absent/delayed response to oral iron treatment. A challenge for the clinicians and pediatricians is the recognition of the disorder among iron deficiency and other microcytic anemias commonly found in pediatric patients. The current treatment of iron refractory iron deficiency anemia is based on parenteral iron administration; in the future, manipulation of the hepcidin pathway with the aim of suppressing it might become an alternative therapeutic approach. PMID:23729726

  15. 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.

  16. 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

  17. Effect of dioxin exposure on several indices of blood redox status in lactating buffalo cows.

    PubMed

    Spagnuolo, Maria Stefania; Sarubbi, Fiorella; Rossetti, Cristina; Grazioli, Giuseppe; Di Meo, Giulia Pia; Iannuzzi, Leopoldo

    2011-05-01

    Dioxins are lipophilic compounds with a small molecular weight and are highly persistent, bioaccumulative and toxic. Dioxin detoxification is associated with an increased production of reactive oxygen species (ROS). In physiological conditions the body is protected against ROS and their toxic products by a wide range of antioxidant systems. We hypothesize that the imbalance between ROS production, associated with dioxin exposure, and the antioxidant defence capacity, may lead to oxidative stress, with consequent increased consumption of antioxidants and accumulation of toxic compounds in blood and tissues. The objective of this study was to evaluate the effect of exposure to dioxins on the plasma redox status of lactating buffalo cows. To this aim, the major liposoluble (retinol and α-tocopherol) and water-soluble (ascorbate) antioxidants, the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, the total antioxidant capacity (TAC), as well as specific protein oxidation markers (protein bound carbonyls and nitro-tyrosine) and lipid oxidation markers (hydroperoxides), were chosen as indices of blood redox status. The concentration of antioxidants, protein-bound carbonyls (PC), nitro-tyrosine (N-Tyr), and hydroperoxides (LPO), the SOD and GPx activity, and the TAC were measured in plasma samples obtained from buffalo cows exposed to environmental levels of dioxins higher (n=21, group A) or lower (n=29; group B) than those permitted. Plasma titres of antioxidants, as measured by HPLC, and the total antioxidant capacity, as measured by trolox equivalents capacity, were higher in group B than in A. Similarly, SOD and GPx activities were higher in group B than in A. Conversely, plasma levels of PC, N-Tyr and LPO, as measured by ELISA, were higher in group A than in B. Our results suggest that exposure to dioxins impairs the plasma antioxidant defence system of lactating buffalo cows, and that metabolic processes associated with dioxin detoxification

  18. Depressive Symptoms, Cardiac Disease Severity, and Functional Status Among Older Patients with Coronary Heart Disease: The Heart and Soul Study

    PubMed Central

    Sin, Nancy L.; Yaffe, Kristine; Whooley, Mary A.

    2014-01-01

    Objectives To compare the relative contributions of depressive symptoms and cardiac disease severity to functional decline among patients with coronary heart disease. Design Longitudinal. Setting Twelve outpatient clinics in the San Francisco Bay Area. Participants Older adults (N = 960; mean age 67) with stable coronary heart disease recruited between 9/2000 and 12/2002. Measurements At baseline, depressive symptoms and angina were assessed by self-report, and left ventricular ejection fraction (LVEF) and exercise capacity were evaluated by echocardiography and exercise treadmill testing. We assessed difficulty performing Activities of Daily Living and Instrumental Activities of Daily Living at baseline and annually for the next 5 years. Covariates included demographics, comorbid conditions, cognitive function, social support, and health behaviors. Five years later, 658 participants returned for follow-up assessments. Results Higher baseline depressive symptoms predicted greater risk of functional decline across 5 years, whereas higher baseline exercise capacity was associated with lower risk of functional decline. Among 658 participants who returned for follow-up, 5-year changes in depressive symptoms and exercise capacity were associated with 5-year changes in functional status. Angina frequency and LVEF were not associated with functional decline or change in functional status, after adjusting for covariates and other predictors. Conclusion Among older adults with coronary heart disease, depressive symptoms and lower exercise capacity predicted functional decline across 5 years. In contrast, other traditional measures of cardiac disease severity (LVEF and angina) were not independently predictive of subsequent functional status. These findings suggest that efforts to ameliorate depressive symptoms may be as important as treating cardiac disease severity to enhance functional status. PMID:25597554

  19. Depressive symptoms, cardiovascular disease severity, and functional status in older adults with coronary heart disease: the heart and soul study.

    PubMed

    Sin, Nancy L; Yaffe, Kristine; Whooley, Mary A

    2015-01-01

    To compare the contributions of depressive symptoms and cardiovascular disease (CVD) severity to functional decline in individuals with coronary heart disease. Longitudinal. Twelve outpatient clinics in the San Francisco Bay area. Older adults (N = 960; mean age 67) with stable coronary heart disease recruited between September 2000 and December 2002. At baseline, depressive symptoms and angina pectoris were assessed according to self-report, and left ventricular ejection fraction (LVEF) and exercise capacity were evaluated using echocardiography and exercise treadmill testing. Difficulty performing activities of daily living and instrumental activities of daily living was assessed at baseline and annually for the next 5 years. Covariates included demographic characteristics, comorbid conditions, cognitive function, social support, and health behaviors. Five years later, 658 participants returned for follow-up assessments. Higher baseline depressive symptoms predicted greater risk of functional decline over 5 years, whereas higher baseline exercise capacity was associated with lower risk of functional decline. In 658 participants who returned for follow-up, 5-year changes in depressive symptoms and exercise capacity were associated with 5-year changes in functional status. Angina pectoris frequency and LVEF were not associated with functional decline or change in functional status, after adjusting for covariates and other predictors. In older adults with coronary heart disease, depressive symptoms and lower exercise capacity predicted functional decline over 5 years. In contrast, other traditional measures of CVD severity (LVEF and angina pectoris) were not independently predictive of subsequent functional status. These findings suggest that efforts to ameliorate depressive symptoms may be as important as treating CVD severity to enhance functional status. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  20. Prevalence and severity of menopause symptoms and associated factors across menopause status in Korean women.

    PubMed

    Yim, Gyeyoon; Ahn, Younjhin; Chang, Yoosoo; Ryu, Seungho; Lim, Joong-Yeon; Kang, Danbee; Choi, Eun-Kyung; Ahn, Jiin; Choi, Yuni; Cho, Juhee; Park, Hyun-Young

    2015-10-01

    The present study investigated the prevalence and severity of menopause symptoms experienced by Korean women aged 44 to 56 years and their associated factors. A cross-sectional study was performed on 2,201 women aged 44 to 56 years in health checkup centers between November 2012 and March 2013. The 29-item Menopause-Specific Quality of Life Questionnaire was used to assess vasomotor, psychosocial, physical, and sexual symptoms related to menopause. The guidelines for the classification of reproductive aging stages proposed at the Stages of Reproductive Aging Workshop were used. Multivariable linear regression analyses were performed to identify factors associated with severity of menopause symptoms. Among participants, 42.6% were premenopausal, 36.7% were perimenopausal, and 20.7% were postmenopausal. Although physical symptoms were the most severe menopause symptoms experienced by premenopausal and perimenopausal women, postmenopausal women reported sexual symptoms as the most bothersome. The mean scores for each domain increased from the premenopausal period through the postmenopausal period (P for trend < 0.001). The regression model revealed that age (for vasomotor and sexual symptoms) and obesity (for vasomotor and physical symptoms) were significantly associated with severity of menopause symptoms (P < 0.05). Physically active women had fewer severe physical symptoms related to menopause than inactive women. Postmenopausal women experience the most severe symptoms. Obesity and physical activity are the main modifiable factors associated with symptom severity. Further studies are needed to examine the effects of physical activity promotion and weight control interventions on preventing menopause symptoms in Korean women.

  1. [Several parameters of the nutritional status of indigenous population of Far North].

    PubMed

    Mironova, G E; Krivoshapkina, Z N; Olesova, L D

    2001-01-01

    Presented are the results of nutrition status of 803 inhabitants of Yakutia both sexes at the age from 20 to 50. 22 per cent of examined men and 42 per cent of examined women had redundant body mass. It relates to high caloric diet and unbalance between consumption and expense of energy. High caloric diet is a cause of hypercholesterinemia and hypertriglyceridemia among young and old people. The most part of residents had insufficiency of vitamin C and beta-carotene in winter. It relates to deficit of fruit and vegetables in diet. 8 per cent of examined men and 30 per cent of examined women had low level of hemoglobin. Thus, rational nutrition is necessary for prophylaxis diseases in the Far North.

  2. Social anxiety and work status: the role of negative metacognitive beliefs, symptom severity and cognitive-behavioural factors.

    PubMed

    Nordahl, Henrik; Wells, Adrian

    2017-06-24

    Psychological health has a profound effect on personal and occupational functioning with Social Anxiety Symptoms in particular having a major effect on ability to work. Recent initiatives have focused on treating psychological illness with cognitive-behavioural models with a view to increasing return to work. However, the psychological correlates of work status amongst individuals with elevated mental health symptoms such as social anxiety are under-explored. This study reports a test of unique predictors of work status drawing on variables that have been given centre stage in cognitive-behavioural models and in the metacognitive model of psychological disorder. The sample consisted of high socially anxious individuals who reported to be working (n = 102) or receiving disability benefits (n = 102). A comparison of these groups showed that those out of work and receiving benefits had greater symptom severity, higher avoidance and use of safety behaviours, greater self-consciousness, and elevated negative metacognitive beliefs and beliefs about the need to control thoughts. However, when the covariance's between these variables were controlled, only negative metacognitive beliefs significantly predicted out-of-work status. Our finding might be important because CBT does not focus on metacognitive beliefs, but targets components that in our analysis had no unique predictive value for work status.

  3. Precursors to potential severe core damage accidents. A status report, 1982--1983

    SciTech Connect

    Forester, J.A.; Mitchell, D.B.; Whitehead, D.W.

    1997-04-01

    This study is a continuation of earlier work that evaluated 1969-1981 and 1984-1994 events affecting commercial light-water reactors. One-hundred nine operational events that affected 51 reactors during 1982 and 1983 and that are considered to be precursors to potential severe core damage are described. All these events had conditional probabilities of subsequent severe core damage greater than or equal to 1.0 x 10{sup {minus}6}. These events were identified by first computer screening the 1982-83 licensee event reports from commercial light-water reactors to select events that could be precursors to core damage. Candidates underwent engineering evaluation that identified, analyzed, and documented the precursors. This report discusses the general rationale for the study, the selection and documentation of events as precursors, and the estimation of conditional probabilities of subsequent severe core damage for the events.

  4. Refractory disease in autoimmune diseases.

    PubMed

    Vasconcelos, Carlos; Kallenberg, Cees; Shoenfeld, Yehuda

    2011-09-01

    Refractory disease (RD) definition has different meanings but it is dynamic, according to knowledge and the availability of new drugs. It should be differentiated from severe disease and damage definitions and it must take into account duration of adequate therapy and compliance of the patient. It can be related to inadequate or inefficacious treatment or to pathogenesis. RD definition has multiple implications to clinical guidelines and to the use of off-label drugs. It should not be regarded as lost cases and prospective studies, registries and clinical trials should be planned.

  5. Efficacy of ketamine in refractory convulsive status epilepticus in children: a protocol for a sequential design, multicentre, randomised, controlled, open-label, non-profit trial (KETASER01)

    PubMed Central

    Rosati, Anna; Ilvento, Lucrezia; L'Erario, Manuela; De Masi, Salvatore; Biggeri, Annibale; Fabbro, Giancarlo; Bianchi, Roberto; Stoppa, Francesca; Fusco, Lucia; Pulitanò, Silvia; Battaglia, Domenica; Pettenazzo, Andrea; Sartori, Stefano; Biban, Paolo; Fontana, Elena; Cesaroni, Elisabetta; Mora, Donatella; Costa, Paola; Meleleo, Rosanna; Vittorini, Roberta; Conio, Alessandra; Wolfler, Andrea; Mastrangelo, Massimo; Mondardini, Maria Cristina; Franzoni, Emilio; McGreevy, Kathleen S; Di Simone, Lorena; Pugi, Alessandra; Mirabile, Lorenzo; Vigevano, Federico; Guerrini, Renzo

    2016-01-01

    Introduction Status epilepticus (SE) is a life-threatening neurological emergency. SE lasting longer than 120 min and not responding to first-line and second-line antiepileptic drugs is defined as ‘refractory’ (RCSE) and requires intensive care unit treatment. There is currently neither evidence nor consensus to guide either the optimal choice of therapy or treatment goals for RCSE, which is generally treated with coma induction using conventional anaesthetics (high dose midazolam, thiopental and/or propofol). Increasing evidence indicates that ketamine (KE), a strong N-methyl-d-aspartate glutamate receptor antagonist, may be effective in treating RCSE. We hypothesised that intravenous KE is more efficacious and safer than conventional anaesthetics in treating RCSE. Methods and analysis A multicentre, randomised, controlled, open-label, non-profit, sequentially designed study will be conducted to assess the efficacy of KE compared with conventional anaesthetics in the treatment of RCSE in children. 10 Italian centres/hospitals are involved in enrolling 57 patients aged 1 month to 18 years with RCSE. Primary outcome is the resolution of SE up to 24 hours after withdrawal of therapy and is updated for each patient treated according to the sequential method. Ethics and dissemination The study received ethical approval from the Tuscan Paediatric Ethics Committee (12/2015). The results of this study will be published in peer-reviewed journals and presented at international conferences. Trial registration number NCT02431663; Pre-results. PMID:27311915

  6. Assessing Same/Different Judgments in Individuals with Severe Intellectual Disabilities: A Status Report.

    ERIC Educational Resources Information Center

    Serna, Richard W.; Dube, William V.; McIlvane, William J.

    1997-01-01

    Summarizes state-of-the-art approaches for assessing visual stimulus same/different judgments in individuals with severe intellectual disabilities. Methodological investigations indicate that one can obtain reliable same/different judgments with a variety of stimuli in virtually anyone for whom a basal score on the Peabody Picture Vocabulary Test…

  7. High-oleic ready-to-use therapeutic food maintains docosahexaenoic acid status in severe malnutrition

    USDA-ARS?s Scientific Manuscript database

    Ready-to-use therapeutic food (RUTF) is the preferred treatment for uncomplicated severe acute malnutrition. It contains large amounts of linoleic acid and little a-linolenic acid, which may reduce the availability of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to the recovering child...

  8. Switching between Abstract Rules Reflects Disease Severity but Not Dopaminergic Status in Parkinson's Disease

    ERIC Educational Resources Information Center

    Kehagia, Angie A.; Cools, Roshan; Barker, Roger A.; Robbins, Trevor W.

    2009-01-01

    This study sought to disambiguate the impact of Parkinson's disease (PD) on cognitive control as indexed by task set switching, by addressing discrepancies in the literature pertaining to disease severity and paradigm heterogeneity. A task set is governed by a rule that determines how relevant stimuli (stimulus set) map onto specific responses…

  9. Sexuality Education Issues and Students Statused Severely Mentally Impaired Regardless of Additional Handicaps.

    ERIC Educational Resources Information Center

    Heler, Ann

    This monograph considers issues in the training of sexuality skills in students with severe mental retardation. An introduction stresses the importance of such skills for these students. A profile of 12 common characteristics of this population and a summary of human commonalities precede the body of the guide. Common manifestations of sexuality…

  10. Switching between Abstract Rules Reflects Disease Severity but Not Dopaminergic Status in Parkinson's Disease

    ERIC Educational Resources Information Center

    Kehagia, Angie A.; Cools, Roshan; Barker, Roger A.; Robbins, Trevor W.

    2009-01-01

    This study sought to disambiguate the impact of Parkinson's disease (PD) on cognitive control as indexed by task set switching, by addressing discrepancies in the literature pertaining to disease severity and paradigm heterogeneity. A task set is governed by a rule that determines how relevant stimuli (stimulus set) map onto specific responses…

  11. Comprehensive Creep and Thermophysical Performance of Refractory Materials

    SciTech Connect

    Ferber, M.K.; Wereszczak, A.; Hemrick, J.A.

    2006-06-29

    Furnace designers and refractory engineers recognize that optimized furnace superstructure design and refractory selection are needed as glass production furnaces are continually striving toward greater output and efficiencies. Harsher operating conditions test refractories to the limit, while changing production technology (such as the conversion to oxy-fuel from traditional air-fuel firing) can alter the way the materials perform [1-3]. Refractories for both oxy- and air-fuel fired furnace superstructures (see Fig. 1) are subjected to high temperatures that may cause them to creep excessively or subside during service if the refractory material is not creep resistant, or if it is subjected to high stress, or both. Furnace designers can ensure that superstructure structural integrity is maintained if the creep behavior of the refractory material is well understood and well represented by appropriate engineering creep models. Several issues limit the abilities of furnace designers to (1) choose the optimum refractory for their applications, (2) optimize the engineering design, or (3) predict the service mechanical integrity of their furnace superstructures. Published engineering creep data are essentially nonexistent for almost all commercially available refractories used for glass furnace superstructures. The limited data that do exist are supplied by the various refractory suppliers. Unfortunately, the suppliers generally have different ways of conducting their mechanical testing, and they interpret and report their data differently. This inconsistency makes it hard for furnace designers to draw fair comparisons between competing grades of candidate refractories. Furthermore, the refractory suppliers' data are often not available in a form that can be readily used for furnace design or for the prediction and design of long-term structural integrity of furnace superstructures. As a consequence, the U.S. Department of Energy (DOE) Industrial Technology Program (ITP

  12. Severity of mumps disease is related to MMR vaccination status and viral shedding.

    PubMed

    Gouma, Sigrid; Hahné, Susan J M; Gijselaar, Daphne B; Koopmans, Marion P G; van Binnendijk, Rob S

    2016-04-07

    During recent years, various mumps outbreaks have occurred among measles, mumps, and rubella (MMR) vaccinated persons in various countries worldwide, including the Netherlands. We studied mumps virus shedding in MMR vaccinated and unvaccinated mumps patients and related these findings to clinical data. In this study, we included 1112 mumps patients of whom diagnostic samples were tested positive in our laboratory between 1 January 2007 and 31 December 2014. We compared mumps virus shedding and severity of disease between patients who had received 2 doses of MMR (n=592) and unvaccinated mumps patients (n=195). Mumps virus shedding in saliva and urine specimens was measured by qPCR. Severity of disease was studied in a subset of patients with clinical data available. Mumps patients who had received 2 MMR doses shed less often mumps virus in their urine than unvaccinated patients. Salivary viral loads were higher at day of onset of disease in twice MMR vaccinated patients with viruria than in twice MMR vaccinated patients without viruria. However, salivary viral loads did not significantly differ between patients who had received 2 MMR doses and unvaccinated patients. Bilateral parotitis and orchitis were less often reported in patients who had received 2 MMR doses than in unvaccinated patients. Furthermore, the prevalence of bilateral parotitis and orchitis was higher among twice MMR vaccinated patients with viruria than among twice MMR vaccinated patients without viruria. MMR vaccination was associated with less severe disease among mumps patients. Systemic spread of virus was associated with more severe disease. The elevated salivary viral loads in patients with systemic mumps disease suggest that these patients pose a higher risk for mumps virus transmission. Our study contributes to the understanding of mumps virus pathogenesis and shows the protective effect of MMR vaccination on severity of disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Changes in Quadriceps Muscle Thickness, Disease Severity, Nutritional Status, and C-Reactive Protein after Acute Stroke.

    PubMed

    Nozoe, Masafumi; Kanai, Masashi; Kubo, Hiroki; Kitamura, Yuka; Yamamoto, Miho; Furuichi, Asami; Takashima, Sachie; Mase, Kyoshi; Shimada, Shinichi

    2016-10-01

    Lower leg muscle wasting is common in stroke patients; however, patient characteristics in the acute phase are rarely studied. This study aimed to examine the relationship between changes in quadriceps muscle thickness and disease severity, nutritional status, and C-reactive protein (CRP) levels after acute stroke. Thirty-one consecutive patients with acute intracerebral hemorrhage or ischemic stroke had quadriceps muscle thickness measured in the paretic and nonparetic limbs within 1 week after admission (first week) and 2 weeks after the first examination (last week) using ultrasonography. We also determined the relationship between the percentage change in muscle thickness and disease severity, nutritional status, and CRP levels on admission. There was a significant correlation between changes in muscle thickness for both paretic and nonparetic sides and National Institutes of Health Stroke Scale (NIHSS) scores (paretic limb: r = -.46, P = .01; nonparetic limb: r = -.54, P = .002, respectively); however, there was no significant correlation with nutritional status on admission. Quadriceps muscle thickness was reduced more in the CRP-positive (≥.3 mg/dL) patients than in the CRP-negative (<.3 mg/dL) patients in the nonparetic limb (positive: -21.4 ± 12.1, negative: -11.4 ± 16.4%; P = .039), but not in the paretic limb (positive: -23.4 ± 9.0, negative: -19.1 ± 15.7; P = .27). A high NIHSS score and a positive CRP on admission were both significantly correlated with decreased quadriceps muscle thickness after acute stroke. Nutritional status on admission was not correlated with changes in quadriceps muscle thickness for these patients. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. Heparin-Related Thrombocytopenia Triggered by Severe Status of Systemic Lupus Erythematosus and Bacterial Infection

    PubMed Central

    Nakajima, Shihoko; Ando, Taiki; Oda, Keisuke; Sugita, Manabu; Maeda, Kunimi; Nakiri, Yutaka

    2016-01-01

    A patient with severe lupus nephritis developed thrombocytopenia during treatment with high-dose steroids. In addition to viral- or disease-induced cytopenia, the pathology was believed to arise from diverse contributing factors, such as thrombotic microangiopathy and heparin-related thrombocytopenia (HIT). By combining plasma exchange therapy and intravenous cyclophosphamide, we successfully controlled the SLE activity and improved the thrombocytopenia. An antecedent bacterial infection or SLE activity is believed to have contributed to the concurrent HIT. PMID:27699076

  15. A new survival status prediction system for severe trauma patients based on a multiple classifier system.

    PubMed

    Sanz, José; Paternain, Daniel; Galar, Mikel; Fernandez, Javier; Reyero, Diego; Belzunegui, Tomás

    2017-04-01

    Severe trauma patients are those who have several injuries implying a death risk. Prediction systems consider the severity of these injuries to predict whether the patients are likely to survive or not. These systems allow one to objectively compare the quality of the emergency services of trauma centres across different hospitals. However, even the most accurate existing prediction systems are based on the usage of a single model. The aim of this paper is to combine several models to make the prediction, since this methodology usually improves the performance of single models. The two currently used prediction systems by the Hospital of Navarre, which are based on logistic regression models, besides the C4.5 decision tree are combined to conform our proposed multiple classifier system. The quality of the method is tested using the major trauma registry of Navarre, which stores information of 462 trauma patients. A 10x10-fold cross-validation model is applied using as performance measures the specificity, sensitivity and the geometric mean between the two former ones. The results are supported by the usage of the Mann-Whitney's U statistical test. The proposed method provides 0.8908, 0.6703 and 0.7661 for sensitivity, specificity and geometric mean, respectively. It slightly decreases the sensitivity of the currently used systems but it notably increases the specificity, which implies a large enhancement on the geometric mean. The same behaviour is found when it is compared versus four classical ensemble approaches and the random forest. The statistical analysis supports the quality of our proposal, since the obtained p-values are less than 0.01 in all the cases. The obtained results show that the multiple classifier systems is the best choice among the considered methods to obtain a trade-off between sensitivity and specificity. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Precursors to potential severe core damage accidents: 1995 A status report

    SciTech Connect

    Belles, R.J.; Cletcher, J.W.; Copinger, D.A.

    1997-04-01

    Ten operational events that affected 10 commercial light-water reactors during 1995 and that are considered to be precursors to potential severe core damage are described. All these events had conditional probabilities of subsequent severe core damage greater than or equal to 1.0 x 10{sup {minus}6}. These events were identified by first computer-screening the 1995 licensee event reports from commercial light-water reactors to identify those events that could potentially be precursors. Candidate precursors were selected and evaluated in a process similar to that used in previous assessments. Selected events underwent engineering evaluation that identified, analyzed, and documented the precursors. Other events designated by the Nuclear Regulatory Commission (NRC) also underwent a similar evaluation. Finally, documented precursors were submitted for review by licensees and NRC headquarters and regional offices to ensure the plant design and its response to the precursor were correctly characterized. This study is a continuation of earlier work, which evaluated 1969-1981 and 1984-1994 events. The report discusses the general rationale for this study, the selection and documentation of events as precursors, and the estimation of conditional probabilities of subsequent severe core damage for the events.

  17. Precursors to potential severe core damage accidents: 1997 -- A status report. Volume 26

    SciTech Connect

    Belles, R.J.; Cletcher, J.W.; Copinger, D.A.; Muhlheim, M.D.; Dolan, B.W.; Minarick, J.W.

    1998-11-01

    This report describes the five operational events in 1997 that affected five commercial light-water reactors (LWRs) and that are considered to be precursors to potential severe core damage accidents. All these events had conditional probabilities of subsequent severe core damage greater than or equal to 1.0 {times} 10{sup {minus}6}. These events were identified by first computer-screening the 1997 licensee event reports from commercial LWRs to identify those events that could be precursors. Candidate precursors were selected and evaluated in a process similar to that used in previous assessments. Selected events underwent engineering evaluation that identified, analyzed, and documented the precursors. Other events designated by the Nuclear Regulatory Commission (NRC) also underwent a similar evaluation. Finally, documented precursors were submitted for review by licensees and NRC headquarters to ensure that the plant design and its response to the precursor were correctly characterized. This study is a continuation of earlier work, which evaluated 1969--1996 events. The report discusses the general rationale for this study, the selection and documentation of events as precursors, and the estimation of conditional probabilities of subsequent severe core damage for the events.

  18. Precursors to potential severe core damage accidents: 1994, a status report. Volume 22: Appendix I

    SciTech Connect

    Belles, R.J.; Cletcher, J.W.; Copinger, D.A.; Vanden Heuvel, L.N.; Dolan, B.W.; Minarick, J.W. |

    1995-12-01

    Nine operational events that affected eleven commercial light-water reactors (LWRs) during 1994 and that are considered to be precursors to potential severe core damage are described. All these events had conditional probabilities of subsequent severe core damage greater than or equal to 1.0 {times} 10{sup {minus}6}. These events were identified by computer-screening the 1994 licensee event reports from commercial LWRs to identify those that could be potential precursors. Candidate precursors were then selected and evaluated in a process similar to that used in previous assessments. Selected events underwent engineering evaluation that identified, analyzed, and documented the precursors. Other events designated by the Nuclear Regulatory Commission (NRC) also underwent a similar evaluation. Finally, documented precursors were submitted for review by licensees and NRC headquarters and regional offices to ensure that the plant design and its response to the precursor were correctly characterized. This study is a continuation of earlier work, which evaluated 1969--1981 and 1984--1993 events. The report discusses the general rationale for this study, the selection and documentation of events as precursors, and the estimation of conditional probabilities of subsequent severe core damage for events. This document is bound in two volumes: Vol. 21 contains the main report and Appendices A--H; Vol. 22 contains Appendix 1.

  19. Status of and prospects for bronchoscopic lung volume reduction for patients with severe emphysema.

    PubMed

    Yu, Hang; Wang, Lijie; Wu, Zhen; Yang, Zhen

    2016-11-15

    Bronchoscopic lung volume reduction (BLVR) is a minimally invasive treatment for severe emphysema, providing treatment options for patients who are unable to undergo lung volume reduction surgery (LVRS) or lung transplantation. Current BLVR techniques include bronchoscopic volume reduction with valve implants, use of a lung volume reduction coil (LVRC), bronchoscopic thermal vapor ablation (BTVA), biological lung volume reduction (BioLVR), and use of airway bypass stents (ABS). To date, several randomized controlled trials of these bronchoscopic therapies have been conducted in patients with emphysema, and bronchoscopic volume reduction with valve implants remains the best approach thus far. Recent studies indicate that BLVR may be of great value in improving lung function, exercise capacity, and quality of life and that BLVR has the potential to replace conventional surgery for patients with severe emphysema. Optimal patient selection and the proper selection of the BLVR technique in accordance with patient characteristics are crucial to the success of BLVR. More multicenter, prospective, randomized controlled trials need to be conducted in the future to optimize the current selection strategy and evaluate the safety, efficiency, and long-term benefit of BLVR techniques.

  20. [Treatment of refractory ascites].

    PubMed

    Martínez, Javier; Albillos, Agustín

    2014-07-01

    Ascites is a common complication of hepatic cirrhosis and portal hypertension. Patients present systemic and splanchnic circulation disorders, which cause central hypovolemia and arterial hypotension, with the subsequent activation of vasoconstrictor systems and increased renal reabsorption of sodium and water. Approximately 5%-10% of patients present refractory ascites. Refractory ascites is considered when it is not controllable with standard dietary (sodium restriction) and diuretic (furosemide up to 160 mg a day and spironolactone up to 400mg a day) treatment or when patients present adverse effects due to diuretics that impede their administration at optimum dosages. The current therapeutic options for these patients are repeated evacuative paracentesis and the percutaneous intrahepatic portosystemic shunt. Despite these treatments, refractory ascites has a poor prognosis; patients should therefore be assessed for liver transplantation.

  1. Epidemiologic Association Between FUT2 Secretor Status and Severe Rotavirus Gastroenteritis in Children in the United States.

    PubMed

    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

    2015-11-01

    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. We investigated whether an association exists between FUT2 secretor status and laboratory-confirmed rotavirus infections in US children. 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. 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. 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. Severe rotavirus gastroenteritis was virtually absent among US children who had a genetic polymorphism that inactivates FUT2 expression on the intestinal epithelium. We observed a strong epidemiologic

  2. 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

  3. Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity

    PubMed Central

    2011-01-01

    Background The relationship between relative metabolic disturbances and developmental disorders is an emerging research focus. This study compares the nutritional and metabolic status of children with autism with that of neurotypical children and investigates the possible association of autism severity with biomarkers. Method Participants were children ages 5-16 years in Arizona with Autistic Spectrum Disorder (n = 55) compared with non-sibling, neurotypical controls (n = 44) of similar age, gender and geographical distribution. Neither group had taken any vitamin/mineral supplements in the two months prior to sample collection. Autism severity was assessed using the Pervasive Development Disorder Behavior Inventory (PDD-BI), Autism Treatment Evaluation Checklist (ATEC), and Severity of Autism Scale (SAS). Study measurements included: vitamins, biomarkers of vitamin status, minerals, plasma amino acids, plasma glutathione, and biomarkers of oxidative stress, methylation, sulfation and energy production. Results Biomarkers of children with autism compared to those of controls using a t-test or Wilcoxon test found the following statistically significant differences (p < 0.001): Low levels of biotin, plasma glutathione, RBC SAM, plasma uridine, plasma ATP, RBC NADH, RBC NADPH, plasma sulfate (free and total), and plasma tryptophan; also high levels of oxidative stress markers and plasma glutamate. Levels of biomarkers for the neurotypical controls were in good agreement with accessed published reference ranges. In the Autism group, mean levels of vitamins, minerals, and most amino acids commonly measured in clinical care were within published reference ranges. A stepwise, multiple linear regression analysis demonstrated significant associations between several groups of biomarkers with all three autism severity scales, including vitamins (adjusted R2 of 0.25-0.57), minerals (adj. R2 of 0.22-0.38), and plasma amino acids (adj. R2 of 0.22-0.39). Conclusion The autism

  4. 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.

  5. The severity, extent and recurrence of necrotizing periodontal disease in relation to HIV status and CD4+ T cell count.

    PubMed

    Phiri, Reality; Feller, Liviu; Blignaut, Elaine

    2010-10-01

    South Africa ranks among the three countries with the highest prevalence of HIV infection in sub-Saharan Africa, with an estimated 29.5% of women attending antenatal clinics being infected. Necrotizing periodontal disease is a well recognized HIV-associated oral condition. The objective of this investigation was to determine a possible correlation between the extent, severity and treatment outcome of necrotizing periodontal disease in relation to a person's HIV status and CD4+ T cell count. Data from 105 consecutive patients presenting with necrotizing periodontal disease at an academic oral health centre in South Africa were analysed. All patients were provided with an opportunity to undergo voluntary counseling and testing for HIV infection, were treated for necrotizing periodontal disease and followed over a period of nine months. The mean age of the cohort was 28 years old (range 12 - 52). Of 98 (93.3%) patients unaware of their HIV serostatus at the initial visit, 59 (56.2%) consented to testing. In total 45 (42.9%) were HIV-seropositive with a mean CD4+ T cell count of 222.7 cells/microl and 14 (13.3%) were HIV-seronegative, with a significantly higher mean CD4+ T cell count of 830 cells/microl (Fisher's exact test, p < 0.001), while the status of 46 (43.8%) remained unknown. In 101 (96.2%) patients, > or = 5 tooth sites were affected, and in 27 (26%) > or = 4 mm of gingival tissue were affected. This study, which included HIV-seropositive, HIV-seronegative and persons of unknown HIV status, revealed no statistical evidence that HIV infection was associated with the extent, severity or relapse of necrotizing periodontal disease. No statistically significant association could be demonstrated between the extent, severity and recurrence of necrotizing periodontal disease and a CD4+ T cell count < or = 200 cells/microl among HIV-seropositive patients.

  6. Towards a European registry of severe allergic reactions: current status of national registries and future needs.

    PubMed

    Worm, M; Timmermans, F; Moneret-Vautrin, A; Muraro, A; Malmheden Yman, I I; Lövik, M; Hattersley, S; Crevel, R

    2010-06-01

    The incidence of severe allergic reactions is largely unknown and information about triggering allergens, aggravating factors, demography of patients and medical care is lacking. A European wide registry could provide a powerful tool to improve the management of severe allergic reactions from both a medical and a public health perspective. Analysis of existing registries regarding the type and quality of data being collected was used to develop a plan for a pan-European registry, including the type of system to be used and the range of data to be entered. Surveillance will provide evidence for the efficacy of risk management measures and may identify the emergence of new allergenic foods, and aid monitoring of novel foods, ingredients and technologies. Patients need a clear indication of factors that may increase their risk of having an adverse reaction, which such a registry can help compile. Based on the collected data, food businesses will be able to develop educational programmes for allergen risk assessment and allergen risk communication. Finally, and most importantly preventive measures can be developed and government agencies receive population based data which may be relevant for legislative purposes.

  7. Severity of household food insecurity is sensitive to change in household income and employment status among low-income families.

    PubMed

    Loopstra, Rachel; Tarasuk, Valerie

    2013-08-01

    Cross-sectional studies have established a relationship between poverty and food insecurity, but little is known about the acute changes within households that lead to changes in food insecurity. This study examined how changes in income, employment status, and receipt of welfare related to change in severity of food insecurity during 1 y among low-income families. In 2005-2007, 501 families living in market and subsidized rental housing were recruited through door-to-door sampling in high-poverty neighborhoods in Toronto. One year later, families were re-interviewed. The final longitudinal analytic sample included 331 families. Within-household change in income, employment, and welfare receipt were examined in relation to change in severity of food insecurity. Severity was denoted by the aggregate raw score on the Household Food Security Survey Module (HFSSM). Analyses were stratified by housing subsidy status owing to differences in characteristics between households. Food insecurity was a persistent problem among families; 68% were food insecure at both interviews. Severity was dynamic, however, as 73.4% answered more or fewer questions affirmatively on the HFFSM between baseline and follow-up. Among market-rent families, a $2000 gain in income during the year and gain of full-time employment were associated with a 0.29 and 1.33 decrease in raw score, respectively (P < 0.01). This study suggests that improvements in income and employment are related to improvements in families' experiences of food insecurity, highlighting the potential for income- and employment-based policy interventions to affect the severity of household food insecurity for low-income families.

  8. [Study on the psychosocial status and related factors in three universities during severe acute respiratory syndrome epidemic in Beijing].

    PubMed

    Liu, Zhao-rui; Huang, Yue-qin; Dang, Wei-min; Liu, Mian; Li, Shu-ran

    2004-07-01

    To investigate the psychosocial status and related factors among university students during severe acute respiratory syndrome (SARS) epidemic in Beijing. By means of stratified cluster sampling, symptom checklist-90 (SCL-90) and questionnaire on general information were applied among 6800 students in three universities in Beijing. There were 6280 valid questionnaires gathered. In order to control and prevent SARS, strict management was conducted in three universities which providing various social supports. Out of the 6280 students, 460 had SCL-90 positive symptoms with a rate of 7.3%. Risk factors of SCL-90 positive symptom were found as follows: major in arts (OR = 2.00), misconception on the control and prevention of SARS (OR = 1.91), considering measures non-effective (OR = 2.25), and do not believe that SARS can be under control (OR = 3.57). Protective factors of SCL-90 positive symptom would include as: being female (OR = 0.77), being graduate students (OR = 0.38), and being not much influenced on study and daily life during the period of strict management (OR = 0.54). Psychosocial status of students was influenced by their knowledge and attitude on SARS. Various social supports might keep the university students to having a healthy psychosocial status.

  9. 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

  10. Fixed ratio (2:1) prolonged-release oxycodone/naloxone combination improves bowel function in patients with moderate-to-severe pain and opioid-induced constipation refractory to at least two classes of laxatives.

    PubMed

    Koopmans, Gineke; Simpson, Karen; De Andrés, Javier; Lux, Eberhard Albert; Wagemans, Michel; Van Megen, Yvonne

    2014-11-01

    The effects of combined oxycodone/naloxone prolonged release tablets (OXN PR) were investigated in patients with moderate-to-severe chronic cancer-related or non-cancer pain. All patients had opioid-induced constipation (OIC) which persisted despite substantial laxative therapy. This pooled analysis included 75 patients with OIC at study entry that was refractory to at least two laxatives with different modes of action. Patients completed randomized, double-blind treatment with OXN PR 20-120 mg/day for either 12 weeks (OXN 9001: non-cancer pain study) or 4 weeks (OXN 2001: cancer-related pain study). Analgesia and bowel function were assessed using the Brief Pain Inventory Short Form and Bowel Function Index (BFI), respectively. Use of laxative medication and safety were assessed throughout the studies. NCT00513656, EudraCT 2005-002398-57, EudraCT 2005-003510-15. Statistically and clinically significant improvements in bowel function were observed following double-blind treatment with OXN PR. Mean (SD) reduction in BFI score was 21.2 (28.8) and comparable in patients with cancer-related (19.0 [28.9]) and non-cancer pain (23.3.[29.0]; P ≤ 0.0002). Furthermore, the proportion of patients with a BFI score within normal range (≤28.8) increased from 9.5% at screening to 43.1% at Day 15 of OXN PR. While all patients used ≥2 laxatives of different classes at screening, during study treatment 36% stopped using laxatives (P < 0.001). OXN PR provided effective analgesia, evidenced by stable pain scores during study treatment, and there were no unanticipated adverse events. OXN PR significantly improved bowel function and reduced the use of laxatives in patients with OIC, previously unresponsive to at least two different classes of laxatives. OXN also provided effective analgesia for patients with moderate-to-severe cancer-related pain and non-cancer-related pain.

  11. History and Current Status of Newborn Screening for Severe Combined Immunodeficiency

    PubMed Central

    Kwan, Antonia; Puck, Jennifer M.

    2015-01-01

    The development of a T cell receptor excision circle (TREC) assay utilizing dried blood spots in universal newborn screening has allowed the early detection of T cell lymphopenia in newborns. Diagnosis of severe combined immunodeficiency (SCID) in affected infants in the neonatal period while asymptomatic permits early treatment and restoration of a functional immune system. SCID was the first immunodeficiency disease to be added to the Recommended Uniform Screening Panel of Core Conditions in the United States in 2010, and is now implemented in 26 states in the U.S. This review covers the development of newborn screening for SCID, the biology of the TREC test, its current implementation in the U.S., new findings for SCID in the newborn screening era, and future directions. PMID:25937517

  12. History and current status of newborn screening for severe combined immunodeficiency.

    PubMed

    Kwan, Antonia; Puck, Jennifer M

    2015-04-01

    The development of a T-cell receptor excision circle (TREC) assay utilizing dried blood spots in universal newborn screening has allowed the early detection of T-cell lymphopenia in newborns. Diagnosis of severe combined immunodeficiency (SCID) in affected infants in the neonatal period, while asymptomatic, permits early treatment and restoration of a functional immune system. SCID was the first immunodeficiency disease to be added to the Recommended Uniform Screening Panel of Core Conditions in the United States in 2010, and it is now implemented in 26 states in the U.S. This review covers the development of newborn screening for SCID, the biology of the TREC test, its current implementation in the U.S., new findings for SCID in the newborn screening era, and future directions.

  13. Dynamic Testing of Gasifier Refractory

    SciTech Connect

    Michael D. Mann; Wayne S. Seames; Devdutt Shukla; Xi Hong; John P. Hurley

    2005-12-01

    The University of North Dakota (UND) Chemical Engineering Department in conjunction with the UND Energy & Environmental Research Center (EERC) have initiated a program to examine the combined chemical (reaction and phase change) and physical (erosion) effects experienced by refractory materials under slagging coal gasification conditions. The goal of this work is to devise a mechanism of refractory loss under these conditions. The controlled-atmospheric dynamic corrodent application furnace (CADCAF) was utilized to simulate refractory/slag interactions under dynamic conditions that more realistically simulate the environment in a slagging coal gasifier than any of the static tests used previously by refractory manufacturers and researchers. High-alumina and high-chromia refractory bricks were tested using slags obtained from two solid fuel gasifiers. Testing was performed at 1475 C in a reducing atmosphere (2% H{sub 2} in N{sub 2}) The CADCAF tests show that high-chrome refractories have greater corrosion resistance than high-aluminum refractories; coal slag readily diffuses into the refractory through its grain boundaries; the refractory grains are more stable than the matrix in the tests, and the grains are the first line of defense against corrosion; calcium and alkali in the slag are more corrosive than iron; and silicon and calcium penetrate the deepest into the refractory. The results obtained from this study are preliminary and should be combined with result from other research programs. In particular, the refractory corrosion results from this study should be compared with refractories removed from commercial gasifiers.

  14. Maternal Vitamin D Status in the Late Second Trimester and the Risk of Severe Preeclampsia in Southeastern China

    PubMed Central

    Zhao, Xin; Fang, Rui; Yu, Renqiang; Chen, Daozhen; Zhao, Jun; Xiao, Jianping

    2017-01-01

    The association between maternal vitamin D deficiency and the risk of severe preeclampsia is still debated. In the present study, we aimed to evaluate vitamin D status in Chinese pregnant women and investigate its correlation with the odds of developing severe preeclampsia. A cohort study was performed on 13,806 pregnant women who routinely visited the antenatal care clinics and subsequently delivered at the Wuxi Maternity and Child Health Hospital. All the subjects in the cohort had their serum 25-hydroxyvitamin D (25(OH)D) concentrations measured during pregnancy. A high prevalence of maternal vitamin D deficiency (25(OH)D < 50 nmol/L) was found. Pregnant women who had different BMIs before pregnancy had significantly different serum concentrations of 25(OH)D. There was also a significant difference in the serum 25(OH)D concentration among pregnant women of different ages. The serum 25(OH)D concentration was significantly lower in pregnant women who subsequently developed severe preeclampsia compared with those who did not. Maternal vitamin D deficiency at 23–28 weeks of gestation was strongly associated with increased odds for severe preeclampsia after adjusting for relevant confounders (adjusted OR, 3.16; 95% CI, 1.77–5.65). Further studies are required to investigate whether vitamin D supplementation would reduce the risk of severe preeclampsia and improve pregnancy outcomes. PMID:28216561

  15. 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

  16. SHS of refractory materials

    NASA Astrophysics Data System (ADS)

    Ismailov, M. B.; Gabayev, Zh. A.

    1993-09-01

    In the SHS production of refractory materials (concretes, coating mixtures) the basic problem is overcoming the scale factor. This is done by imparting a granular structure to the mass being synthesized. Requirements for the granular and chemical composition of the filler are obtained.

  17. Improved status following behavioural intervention in a case of severe dysarthria with stroke aetiology.

    PubMed

    Mackenzie, Catherine; Lowit, Anja

    2012-08-01

    There is little published intervention outcome literature concerning dysarthria acquired from stroke. Single case studies have potential for more detailed specification and interpretation than is generally possible in larger studies so are informative for clinicians dealing with similar cases. Such research also contributes to planning of larger scale investigations. Behavioural intervention is described which was carried out between 7-9 months after stroke with a 69-year-old man with severe dysarthria. Pre-intervention stability between 5-7 months contrasted with post-intervention gains. Significant improvement was demonstrated using randomized, blinded assessment by 10 judges on measures of word and reading intelligibility and communication effectiveness in conversation. A range of speech analyses were undertaken (rate, pause, and intonation characteristics in connected speech and single word phonetic transcription), with the aim of identifying speech components which might explain the listeners' perceptions of improvement. Changes were detected mainly in parameters related to utterance segmentation and intonation. The basis of post-intervention improvement in dysarthria is complex, both in terms of the active therapeutic dimensions and also the specific speech alterations which account for changes to intelligibility and effectiveness.

  18. Oxidative status and the severity of clinical symptoms in patients with post-traumatic stress disorder.

    PubMed

    Borovac Štefanović, Leda; Kalinić, Dubravka; Mimica, Ninoslav; Beer Ljubić, Blanka; Aladrović, Jasna; Mandelsamen Perica, Marina; Curić, Maja; Grošić, Petra Folnegović; Delaš, Ivančica

    2015-01-01

    The aim of this study was to measure the parameters of oxidative stress in the blood of patients with post-traumatic stress disorder. The study included 80 male war veterans who participated actively in the Homeland war in Croatia. Volunteers were divided into two groups: 50 veterans diagnosed with post-traumatic stress disorder and 30 without diagnosis. The self-assessment Hospital Anxiety and Depression Scale and the Beck Depression Inventory were used to detect the severity of depression and anxiety in the post-traumatic stress disorder patients. Catalytic concentrations of superoxide dismutase and glutathione peroxidase in erythrocytes and the concentration of malondialdehyde in serum were measured spectrophotometrically. Although the catalytic concentrations of erythrocyte superoxide dismutase and erythrocyte glutathione peroxidase were within the reference range for both groups, the values obtained for the post-traumatic stress disorder group were significantly lower (P<0.001). For serum malondialdehyde concentrations, no statistically significant differences between the groups were found. Lower catalytic concentrations of erythrocyte superoxide dismutase and erythrocyte glutathione peroxidase in patients with post-traumatic stress disorder may indicate a weaker response to oxidative stress due to impaired enzyme activity and/or decreased synthesis. Conversely, no significant changes in serum malondialdehyde concentrations suggest a compensated balance and adaptive response to (oxidative) stress. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  19. High oleic ready-to-use therapeutic food maintains docosahexaenoic acid status in severe malnutrition: a randomized, blinded trial

    PubMed Central

    Hsieh, Ji-Cheng; Liu, Lei; Zeilani, Mamane; Ickes, Scott; Trehan, Indi; Maleta, Ken; Craig, Christina; Thakwalakwa, Chrissie; Singh, Lauren; Brenna, J. Thomas; Manary, Mark J.

    2015-01-01

    Objective Ready-to-use therapeutic food (RUTF) is the preferred treatment for uncomplicated severe acute malnutrition. RUTF contains large amounts of linoleic acid and very little α-linolenic acid, which may reduce the availability of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to the recovering child. A novel high oleic RUTF (HO-RUTF) was developed with less linoleic acid to determine its effect on DHA and EPA status. Methods We conducted a prospective, randomized, double-blinded, clinical effectiveness trial treating rural Malawian children with severe acute malnutrition. Children were treated with either HO-RUTF or standard RUTF. Plasma phospholipid (PL) fatty acid status was measured upon enrollment and after 4 weeks and compared between the two intervention groups. Results Among the 141 children enrolled, 48/71 receiving HO-RUTF and 50/70 receiving RUTF recovered. Plasma PL samples were analyzed from 43 children consuming HO-RUTF and 35 children consuming RUTF. The change in DHA content during the first 4 weeks was +4% and −25% in the HO-RUTF and RUTF groups, respectively (P = 0.04). For EPA, the change in content was 63% and −24% in the HO-RUTF and RUTF groups (P < 0.001). For arachidonic acid, the change in content was −3% and 13% in the HO-RUTF and RUTF groups (P < 0.009). Conclusions The changes in DHA and EPA seen in the children treated with HO-RUTF warrant further investigation as they suggest HO-RUTF support improved PUFA status, necessary for neural development and recovery. PMID:25633498

  20. Depression, anxiety and obsessive-compulsive symptoms in relation to nutritional status and outcome in severe anorexia nervosa.

    PubMed

    Mattar, Lama; Thiébaud, Marie-Raphaele; Huas, Caroline; Cebula, Christelle; Godart, Nathalie

    2012-12-30

    Depression, anxiety and obsessive-compulsive disorder are frequently reported to co-occur with anorexia nervosa (AN). There is clinical consensus that depressive symptoms and anxiety may in part be sequelae of malnutrition in AN. However, evidence-based data are still very rare. The present study among severe AN patients investigates links between these psychological variants and nutritional status at admission and subsequent to nutritional rehabilitation. Twenty-four women with AN diagnosed according to the Diagnostic and Statistical Manual IV (DSM-IV) were included prospectively and consecutively at hospitalisation. Nutritional status was assessed by body mass index (BMI). Several psychological aspects were assessed using various scales for depression, anxiety, social phobia, obsessive and eating behaviour symptoms. Follow-up weights and heights at 4-12 years after hospital discharge were measured in 18 patients. BMI and all the scores except the Yale-Brown obsessive-compulsive scale (Y-BOCS) showed significant improvement between admission and discharge. This study highlights the fact that some of the depressive and anxiety symptoms at least partially decrease with nutrition rehabilitation. The improvement in the scores on the psychometric scales between admission and discharge was not correlated with BMI improvement. Psychometric scores at admission and at discharge were not correlated with BMI at follow-up. BMI at follow-up was correlated with minimum lifetime BMI (r=0.486, P=0.04). Future studies should use a better indicator for nutritional status than BMI alone, and should also consider the initial degree of weight loss and the rate at which weight was lost.

  1. Association between iron status, iron deficiency anaemia, and severe early childhood caries: a case–control study

    PubMed Central

    2013-01-01

    Background Severe tooth decay is known to affect the health and well-being of young children. However, little is known about the influence of Severe Early Childhood Caries (S-ECC) on childhood nutritional status. The purpose of this study was to contrast ferritin and haemoglobin levels between preschoolers with S-ECC and caries-free controls. Methods Children were recruited as part of a larger case–control study examining differences in nutritional status between those with and without S-ECC. Preschoolers with S-ECC were recruited on the day of their dental surgery, while caries-free controls were recruited from the community. Parents completed a questionnaire and the child underwent venipuncture. The study was approved by the University’s Health Research Ethics Board. Statistics included descriptive, bivariate and logistic regression analyses. A p value ≤ .05 was significant. A total of 266 children were recruited; 144 with S-ECC and 122 caries-free. Results The mean age was 40.8 ± 14.1 months. The mean ferritin concentration for all children was 29.6 ± 17.9 μg/L while the mean haemoglobin level was 115.1 ± 10.1 g/L. Children with S-ECC were significantly more likely to have low ferritin (p=.033) and low haemoglobin levels (p>.001). Logistic regression analyses revealed that children with S-ECC were nearly twice as likely to have low ferritin levels and were over six times more likely to have iron deficiency anaemia than caries-free controls. Conclusions Children with S-ECC appear to be at significantly greater odds of having low ferritin status compared with caries-free children and also appear to have significantly lower haemoglobin levels than the caries-free control group. Children with S-ECC also appear to be at significantly greater odds for iron deficiency anaemia than cavity-free children. PMID:23388209

  2. Characteristics of a large mumps outbreak: Clinical severity, complications and association with vaccination status of mumps outbreak cases

    PubMed Central

    Zamir, C Stein; Schroeder, H; Shoob, H; Abramson, N; Zentner, G

    2015-01-01

    In recent years, large mumps outbreaks, involving mainly adolescents and young adults, have re-emerged in several countries. We investigated a large mumps outbreak, evaluated the association between mumps clinical severity (complications, hospitalization) and vaccination status (number of previous measles, mumps and rubella - MMR vaccine doses), and assessed vaccine effectiveness. The first mumps cases emerged in an ultra-orthodox boys' school in Jerusalem and were epidemiologically linked to the mumps outbreak in New York. Overall, 3130 mumps cases were notified in the Jerusalem district during September 2009-August 2011 (median age 13y, 64% males). Most cases were reported from community clinics. Patients with systemic symptoms and/or complications (419, 13.4%) were either hospitalized (n = 79) or treated in an emergency medical center (n = 340). The main complications included orchitis (3.8% males> age 12y) and meningoencephalitis (0.5%). The mumps virus genotype was G5. The distribution of previous MMR vaccine doses (n = 0,1,2) was: 24.8%, 28.3% and 46.9%, respectively. The number of previous vaccine doses was inversely associated with clinical severity. Adjusted values for MMR vaccine effectiveness against complications were estimated as 52.1% (95% CI −4 −78%) for one vaccine dose and 62.7% (95% CI 25.7–81.3%) for 2 doses. The outbreak was characterized by predominance of male students; the majority of whom had been previously vaccinated. The reported complication rate was relatively low. Vaccination status was associated with age and disease severity. The combination of limited mumps vaccine effectiveness and the specific school setting (dense learning and living conditions) probably contributed to the disease spread. PMID:25874726

  3. The status of the fourth ventricle and ambient cisterns predict outcome in moderate and severe traumatic brain injury.

    PubMed

    Jacobs, Bram; Beems, Tjemme; van der Vliet, Ton M; Borm, George F; Vos, Pieter E

    2010-02-01

    Computed tomography (CT) of the head has become the diagnostic tool of choice, particularly for moderate and severe traumatic brain injury (TBI). Various CT characteristics are associated with outcome, and may therefore be used as outcome predictors. One of the most prominent predictors appears to be the status of the basal cisterns. This study describes the prognostic value of the appearance of individual cisterns and ventricles in relation to that of the basal cisterns. Further, we determine the interrater and intrarater reliability in the evaluation of the cisterns and ventricles. All consecutive moderate and severe adult TBI patients admitted to our hospital were included in this study as part of the prospective Radboud University Brain Injury Cohort Study (RUBICS). Outcome was assessed at 6 months post-trauma using the Glasgow Outcome Scale-Extended (GOS-E). The predictive value of cisterns and ventricles was determined using multivariate binary logistic regression analysis. We included 126 moderate and 574 severe TBI patients. Absence (complete obliteration), but also compression of the ambient cisterns and/or the fourth ventricle were strongly related to unfavorable outcome and death and emerged as the only significant outcome predictors after multivariate analysis. The assessment of the ambient cisterns and the fourth ventricle had a satisfactory inter- and intrarater reliability (kappa coefficients: 0.80-0.95). We conclude that, because obliteration of the ambient cisterns and the fourth ventricle both are better than the status of the basal cisterns as outcome predictors, they might be used in CT prediction models in cases of moderate and severe TBI.

  4. Characteristics of a large mumps outbreak: Clinical severity, complications and association with vaccination status of mumps outbreak cases.

    PubMed

    Zamir, C Stein; Schroeder, H; Shoob, H; Abramson, N; Zentner, G

    2015-01-01

    In recent years, large mumps outbreaks, involving mainly adolescents and young adults, have re-emerged in several countries. We investigated a large mumps outbreak, evaluated the association between mumps clinical severity (complications, hospitalization) and vaccination status (number of previous measles, mumps and rubella - MMR vaccine doses), and assessed vaccine effectiveness. The first mumps cases emerged in an ultra-orthodox boys' school in Jerusalem and were epidemiologically linked to the mumps outbreak in New York. Overall, 3130 mumps cases were notified in the Jerusalem district during September 2009-August 2011 (median age 13y, 64% males). Most cases were reported from community clinics. Patients with systemic symptoms and/or complications (419, 13.4%) were either hospitalized (n = 79) or treated in an emergency medical center (n = 340). The main complications included orchitis (3.8% males> age 12y) and meningoencephalitis (0.5%). The mumps virus genotype was G5. The distribution of previous MMR vaccine doses (n = 0,1,2) was: 24.8%, 28.3% and 46.9%, respectively. The number of previous vaccine doses was inversely associated with clinical severity. Adjusted values for MMR vaccine effectiveness against complications were estimated as 52.1% (95% CI -4 -78%) for one vaccine dose and 62.7% (95% CI 25.7-81.3%) for 2 doses. The outbreak was characterized by predominance of male students; the majority of whom had been previously vaccinated. The reported complication rate was relatively low. Vaccination status was associated with age and disease severity. The combination of limited mumps vaccine effectiveness and the specific school setting (dense learning and living conditions) probably contributed to the disease spread.

  5. 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.

  6. PENETRATION OF COAL SLAGS INTO HIGH-CHROMIA REFRACTORIES

    SciTech Connect

    Longanbach, Sara C.; Matyas, Josef; Sundaram, S. K.

    2009-10-05

    Slagging coal gasifiers are used for the production of electricity and synthetic gases, as well as chemicals. High temperatures in the reaction chamber, typically between 1250ºC and 1600ºC, high pressure, generally greater than 400 psi, and corrosive slag place severe demands on the refractory materials. Slag produced during the combustion of coal flows over the refractory surface and penetrates the porous material. Slag penetration is typically followed by spalling of a brick that significantly decreases the service life of gasifier refractories. Laboratory tests were conducted to determine the penetration depth of slags into high-chromia refractories as a function of time and temperature for various refractory-slag combinations.

  7. Refractory Glass Seals for SOFC

    SciTech Connect

    Chou, Y. S.; Stevenson, Jeffry W.

    2011-07-01

    One of the critical challenges facing planar solid oxide fuel cell (SOFC) technology is the need for reliable sealing technology. Seals must exhibit long-term stability and mechanical integrity in the high temperature SOFC environment during normal and transient operation. Several different approaches for sealing SOFC stacks are under development, including glass or glass-ceramic seals, metallic brazes, and compressive seals. Among glass seals, rigid glass-ceramics, self-healing glass, and composite glass approaches have been investigated under the SECA Core Technology Program. The U.S. Department of Energy's Pacific Northwest National Laboratory (PNNL) has developed the refractory glass approach in light of the fact that higher sealing temperatures (e.g., 930-1000 degrees C) may enhance the ultimate in-service bulk strength and electrical conductivity of contact materials, as well as the bonding strength between contact materials and adjacent SOFC components, such as interconnect coatings and electrodes. This report summarizes the thermal, chemical, mechanical, and electrical properties of the refractory sealing glass.

  8. Severe hemispatial neglect as a manifestation of seizures and nonconvulsive status epilepticus: utility of prolonged EEG monitoring.

    PubMed

    Schomer, Andrew C; Drislane, Frank W

    2015-04-01

    Seizures and status epilepticus causing hemispatial neglect syndromes are seldom diagnosed, in part because, without motor signs, EEGs are not performed. Also, nonconvulsive seizures are often intermittent and missed on a single EEG. Two patients had severe neglect syndromes thought due to strokes. Correct diagnosis of epileptic seizures required longer-term EEG monitoring. Review of clinical history, neurologic examination, imaging, and findings on prolonged EEG monitoring. A patient with a new onset of a profound left neglect had normal strength and language use, with no obvious clinical seizures. A right hemisphere embolic stroke was diagnosed, but MRI with diffusion-weighted imaging showed no evidence of ischemia. The initial EEG showed marked right parietal voltage suppression, with subsequent brief electrographic seizures and later, right parietal periodic discharges. The second patient had an earlier right subdural hematoma and focal motor seizures but was admitted with a new neglect syndrome and no clear clinical seizures. Head computed tomography showed no new lesion. EEG showed frequent right parieto-temporal epileptiform discharges and electrographic seizures. The neglect syndromes resolved with anticonvulsant treatment, but in both cases, electrographic seizures were intermittent, and there was no strict correlation between the clinical deficit and EEG manifestations of seizures. Infrequently, the sudden onset of new hemispatial neglect can be caused by nonconvulsive seizures and nonconvulsive status epilepticus, even when there is no weakness and no clear clinical seizure activity. Nonconvulsive status epilepticus can cause primarily perceptual and cognitive syndromes. The correlation between the clinical deficits and seizure activity on the EEG, however, is imprecise. A single EEG may miss seizure activity, and repeated or prolonged EEG recording may be necessary to make the diagnosis.

  9. Self-Organizing Maps with Refractory Periods

    SciTech Connect

    Neme, Antonio; Mireles, Victor

    2008-11-06

    Self-organizing map (SOM) has been studied as a model of map formation in the brain cortex. However, the original model present several oversimplifications. For example, neurons in the cortex present a refractory period in which they are not able to be activated, restriction that should be included in the SOM if a better model is to be achieved. Although several modifications have been studied in order to include this biological restriction to the SOM, they do not reflect biological plausibility. Here, we present a modification in the SOM that allows neurons to enter a refractory period (SOM-RP) if they are the best matching unit (BMU) or if they belong to its neighborhood. This refractory period is the same for all affected neurons, which contrasts with previous models. By including this biological restriction, SOM dynamics resembles in more detail the behavior shown by the cortex, such as non-radial activity patterns and long distance influence, besides the refractory period. As a side effect, two error measures are lower in maps formed by SOM-RP than in those formed by SOM.

  10. The Risk of Occupational Injury Increased According to Severity of Noise Exposure After Controlling for Occupational Environment Status in Korea

    PubMed Central

    Yoon, Jin-Ha; Roh, Jaehoon; Kim, Chi-Nyon; Won, Jong-Uk

    2016-01-01

    Objectives: The aim of this study was to examine the relationship between noise exposure and risk of occupational injury. Materials and Methods: Korean National Health and Nutrition Examination Survey was used for the current study. Self-report questionnaires were used to investigate occupational injury and exposure to noise, chemicals, and machines and equipments. Results: In separate analyses for occupation and occupational hazard, the proportion of occupational injuries increased according to severity of noise exposure (all P < 0.05). Compared to the non-exposure group, the respective odds ratio (95% confidence intervals) for occupational injury was 1.39 (1.07–1.80) and 1.67 (1.13–2.46) in the mild and severe noise exposure groups, after controlling for age, gender, sleep hours, work schedule (shift work), and exposure status to hazardous chemicals and hazardous machines and equipments. Conclusions: The current study highlights the association between noise exposure and risk of occupational injury. Furthermore, risk of occupational injury increased according to severity of noise exposure. PMID:27991467

  11. Refractory rheumatoid vasculitis.

    PubMed

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

    2016-11-01

    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.

  12. 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.

  13. 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

  14. [Translation and validation of an instrument for evaluation of severity of symptoms and the functional status in carpal tunnel syndrome].

    PubMed

    de Campos, Carmelinda Correia; Manzano, Gilberto Mastrocola; de Andrade, Lucilia Bannwart; Castelo Filho, Adauto; Nóbrega, João Antonio Maciel

    2003-03-01

    The objective of the present study was to translate, to do cultural equivalence and validation of the Levine et al. (1993) or Boston Carpal Tunnel Questionnaire (BCTQ) to Portuguese. The BCTQ application to patients, selected by the question "What was the reason that brought you to look for a physician and that led him to ask this examination?" showed very good reproducibility. The validity was measured through the comparison of the severity symptoms scores (SSS) and the functional status scores (FSS) with the results of grip forces, Minnesota, two point discrimination, Semmes-Weinstein filaments perception and sensory conduction at the median nerve. The internal consistency was evaluated through Chronbach's alpha coefficient comparing the SSS and the FSS. The measuring properties were evaluated through paired t-test between pre and pos-surgical scores. Reproducibility, internal consistency, validation and measuring properties of the translated BCTQ were similar to those found by Levine et al. with the original version.

  15. [Severe vitamin D deficiency in children from Punta Arenas, Chile: Influence of nutritional status on the response to supplementation].

    PubMed

    Brinkmann, Karin; Le Roy, Catalina; Iñiguez, Germán; Borzutzky, Arturo

    2015-01-01

    There is a high risk of vitamin D (VD) deficiency in the population of southern Chile that can be treated with VD supplements. Weight excess (WE) can influence the response to supplements. To study the prevalence of VD deficiency and the effect of cholecalciferol (VD3) supplements in healthy children from Punta Arenas, Chile, and evaluate a possible association with nutritional status. Demographic and anthropometric data, as well as laboratory assessment of serum 25-hidroxyvitamin D (25OHD) and other bone metabolism parameters were evaluated. After baseline evaluation, children were supplemented with VD3 1600 IU/day for one month, after which 25OHD was retested. Of the 108 children studied, 50% were boys, and had a mean age of 9.6±0.5 years. Nutritional assessment showed that 39% had normal weight, 46% were overweight, and 15% were obese. Median 25OHD was 10.9ng/ml: 96.3% had deficiency (<20ng/ml) and 3.7% insufficiency (20-29ng/ml). Severe deficiency was found in 62% (<12ng/ml). Baseline 25OHD was not affected by nutritional status. After supplementation, median 25OHD was 17.5ng/ml: 62% had deficiency, 36% insufficiency, and 2% sufficiency (>30ng/ml). Children with WE had a significantly lower increase in 25OHD than children with normal weight (5±5.5 vs. 7.7±4.9, p=03). Children with WE may require 32% higher VD dose than normal weight children to attain the same 25OHD concentration. Chilean schoolchildren from Punta Arenas have high prevalence of WE and VD deficiency, with a majority in the range of severe VD deficiency. WE interferes in the response to VD supplementation, leading to a lower increase in 25OHD. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Birmingham epidermolysis severity score and vitamin D status are associated with low BMD in children with epidermolysis bullosa.

    PubMed

    Rodari, G; Guez, S; Manzoni, F; Chalouhi, K K; Profka, E; Bergamaschi, S; Salera, S; Tadini, G; Ulivieri, F M; Spada, A; Giavoli, C; Esposito, S

    2017-04-01

    Bone status impairment represents a complication of generalized forms of epidermolysis bullosa (EB); however, the prevalence and the main determinants of this event in localized forms remain poorly defined. Birmingham epidermolysis bullosa severity (BEBS) score and 25-hydroxyvitamin D levels are strongly associated with low bone mass, suggesting that vitamin D may play a potential beneficial role in bone health. Further longitudinal studies are needed in order to confirm this hypothesis. Bone status impairment represents a complication of generalized forms of EB; thus, we aimed to estimate the prevalence of low bone mass, to examine mineralization differences in various EB subtypes and to identify the most important determinants of bone impairment in children with either generalized or localized EB. An observational study of 20 children (11 males; mean age ± standard deviation, 11.7 ± 3.9 years) with EB was performed. Clinical history, physical examination, laboratory studies, X-ray of the left hand and wrist for bone age, and dual energy X-ray absorptiometry scans of the lumbar spine were obtained. Areal bone mineral density (aBMD Z-scores) and bone mineral apparent density were related to the BEBS score. Areal BMD Z-score (mean -1.82 ± 2.33, range, -7.6-1.7) was reduced (<-2 SD) in 8 patients (40%), whereas aBMD Z-score adjusted for bone age was low in 7 patients (35%). BEBS score and 25-hydroxyvitamin D serum levels were the most important elements associated with aBMD (P = 0.0001 and P = 0.016, respectively). A significant correlation between the aBMD Z-score and area of skin damage, insulin-like growth factor-1, C-reactive protein, and sodium serum levels was also found. Low aBMD can be considered a systemic complication of EB, primarily associated with BEBS score and 25-hydroxyvitamin D levels. Therefore, longitudinal evaluation of bone status is ongoing in these patients to define whether vitamin D supplementation would prevent, or at least

  17. High temperature barrier coatings for refractory metals

    SciTech Connect

    Malone, G.A.; Walech, T.

    1995-06-01

    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.

  18. 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.

  19. Low Health System Performance, Indigenous Status and Antivenom Underdosage Correlate with Spider Envenoming Severity in the Remote Brazilian Amazon

    PubMed Central

    Sampaio, Vanderson Souza; Gomes, André Alexandre; Silva, Iran Mendonça; Sachett, Jacqueline; Ferreira, Luiz Carlos Lima; Oliveira, Sâmella; Sabidò, Meritxell; Chalkidis, Hipócrates; Barbosa Guerra, Maria Graças Vale; Salinas, Jorge Luis; Wen, Fan Hui; Lacerda, Marcus Vinícius Guimarães; Monteiro, Wuelton Marcelo

    2016-01-01

    Background A better knowledge of the burden and risk factors associated with severity due to spider bites would lead to improved management with a reduction of sequelae usually seen for this neglected health problem, and would ensure proper use of antivenoms in remote localities in the Brazilian Amazon. The aim of this study was to analyze the profile of spider bites reported in the state of Amazonas in the Western Brazilian Amazon, and to investigate potential risk factors associated with severity of envenomation. Methodology/Principal Findings We used a case-control study in order to identify factors associated with spider bite severity in the Western Brazilian Amazon from 2007 to 2014. Patients evolving to any severity criteria were considered cases and those with non-severe bites were included in the control group. All variables were retrieved from the official Brazilian reporting systems. Socioeconomical and environmental components were also included in a multivariable analysis in order to identify ecological determinants of incidence and severity. A total of 1,181 spider bites were recorded, resulting in an incidence of 4 cases per 100,000 person/year. Most of the spider bites occurred in males (65.8%). Bites mostly occurred in rural areas (59.5%). The most affected age group was between 16 and 45 years old (50.9%). A proportion of 39.7% of the bites were related to work activities. Antivenom was prescribed to 39% of the patients. Envenomings recorded from urban areas [Odds ratio (OR) = 0.40 (95%CI = 0.30–0.71; p<0.001)] and living in a municipality with a mean health system performance index (MHSPI >median [OR = 0.64 (95%CI = 0.39–0.75; p<0.001)] were independently associated with decreased risk of severity. Work related accidents [OR = 2.09 (95%CI = 1.49–2.94; p<0.001)], Indigenous status [OR = 2.15 (95%CI = 1.19–3.86; p = 0.011)] and living in a municipality located >300 km away from the state capital Manaus [OR = 1.90 (95%CI = 1.28–2.40; p<0

  20. Predictors and course of vocational status, income, and quality of life in people with severe mental illness: a naturalistic study.

    PubMed

    Nordt, Carlos; Müller, Brigitte; Rössler, Wulf; Lauber, Christoph

    2007-10-01

    Due to high unemployment rates, people with mental illness are at risk of poverty and are deprived of the social and psychological functions of work, such as the provision of social support, structuring of time, and self-esteem, with a negative effect on their perceived quality of life (QoL). Two distinct processes are held responsible for the low work force participation of people with mental illness: 'Social underachievement' and 'social decline'. Social underachievement signifies that, due to early illness onset, the educational attainment of people with mental illness is low and entry to the labor market fails. Social decline, on the other hand, describes the loss of competitive employment after illness onset, followed by prolonged periods of unemployment and difficulties to re-enter the labor market. This study examines how social underachievement and decline are reflected in the course of vocational status, income, and QoL of people with severe mental illness in the years after a psychiatric admission in a naturalistic longitudinal design. A total of 176 participants diagnosed with schizophrenia or affective disorders were interviewed during an index hospitalization in two large psychiatric hospitals in Zurich. Follow-up interviews were conducted 12 and 30 months after. Random coefficient models (multilevel models) were used to examine simultaneously the predictors and course of the variables of interest. A low number of psychiatric hospitalizations, a higher educational degree, a diagnosis of schizophrenia, and years of work experience predicted a higher vocational status. Vocational status decreased in first-admission participants with prolonged hospitalizations during the follow-up period. Income did not change over time and was positively influenced by a higher age of illness onset, competitive employment, higher education, and not having had a longer hospitalization recently. Subjective QoL significantly improved and was rated higher by people with any

  1. Association between the nutritional status and the severity of sarcopenia among community-dwelling elderly Japanese people.

    PubMed

    Komai, Satsuki; Watanabe, Yutaka; Fujiwara, Yoshinori; Kim, Hunkyung; Edahiro, Ayako; Kawai, Hisashi; Yoshida, Hideyo; Obuchi, Shuichi; Tanaka, Yayoi; Hirano, Hirohiko

    2016-01-01

    To investigate the association between nutritional evaluation indices (body mass index, albumin, and weight loss) and sarcopenia severity among community-dwelling elderly people in Japan. The subjects consisted of 758 community-dwelling elderly people ≥65 years of age, categorized into two groups by based on Operation of long life medical care system (medical care system for elderly in the latter stage of life), the cut-off value for age used was 75. The outcome measures were basic characteristics, anthropometric measures, physical function, and blood biochemistry (five assessments). The appendicular skeletal muscle mass was calculated via a bioelectrical impedance analysis. The subjects were categorized into three groups by the body mass index (BMI) [BMI 3 group]. The cut-off value for albumin used was 3.8 g/dL [A1b 2 group]. Weight loss was assessed using item 11 on the Kihon check list: "Have you experienced more than 2-3 kg weight loss over the past 6 months? Yes=1, No=0." [weight loss 2 group]. Sarcopenia was defined based on the European Working Group on Sarcopenia in Older People definition, using the Asian Working Group for Sarcopenia cut-off values. All subjects were then categorized into four groups based on their sarcopenia status: non-sarcopenic (non-), pre-sarcopenic (pre-), sarcopenic (sarco-), or severely sarcopenic (severe-) [sarco4 group]. The prevalence of sarcopenia and severe sarcopenia in men was 5.6% (n=18) and 1.2% (n=4), respectively, and in women was 7.8% (n=34) and 1.6% (n=7), respectively. The analysis showed that, among the people (>75 years of age) with normal BMI (18.5-25.0), 10.4%-15.6% were in the Sarco group. Further, among women over 75 years of age with BMI >25.0, 5.7% (n=2) were in the Sarco group. There was a significant association between weight loss and sarcopenia severity in older men. No significant association between albumin levels and sarcopenia severity was observed. 80.0% of weight-loss was presented in above BMI 18

  2. Relationship between Nutritional Status and the Severity of Huntington’s Disease. A Spanish Multicenter Dietary Intake Study.

    PubMed

    Cubo, Esther; Rivadeneyra, Jéssica; Armesto, Diana; Mariscal, Natividad; Martinez, Asunción; Camara, Rafael J

    2015-01-01

    Little is known about the impact of nutrition status on Huntington’s disease (HD) severity. To analyze the association of nutritional factors with HD severity. Observational, cross-sectional, national multicenter study. Participants were selected from a Spanish cohort of patients who participate in the European Huntington Disease Network (EHDN). The frequency of food consumption, caloric and nutrients intake in patients with HD were assessed using validated questionnaires for the Spanish population, and calculated using Alimentaci´on and Salud, version 2.0, and the Spanish Dietary Recommended Intakes were used as the gold standard. Disease severity was assessed using the Unified HD Rating Scale (UHDRS) and Total Functional Capacity (TFC). Logistic regression models were performed using the TFC as the dependent variable, and the macro-micronutrients as the independent variables, adjusted for age, gender, education, physical activity, and intake of supplements. Two hundred and twenty four patients with HD were included (59% women), mean age of 47.41±14.26 years, median TFC 9 (3–13), median UHDRS motor score of 33.5 (3.75–56), 75.8% with normal-high caloric intake, 55.4% normal BMI, and 54.4% with medium-high adherence to the Mediterranean diet. Compared to patients with mild-moderate HD, patients with severe HD had higher caloric intake (p = 0.02), and similar BMI (p = 0.33). Advanced HD was associated with higher intake of water-soluble vitamins (OR = 2.08; 95% CI = 1.12–3.85, p = 0.02), and minerals (OR = 1.86; 95% CI = 1.09– 3.19, p = 0.02). An adequate dietary intake prevents against weight loss in patients with advanced HD, but it is not associated with better functional state.

  3. [Influence of educational status, burn area and coping behaviors on the complication of psychological disorders in severely burned patients].

    PubMed

    Cheng, Hua; Li, Xiao-jian; Cao, Wen-juan; Chen, Li-ying; Zhang, Zhi; Liu, Zhi-he; Yi, Xian-feng; Lai, Wen

    2013-04-01

    To discuss how the educational status, burn area and coping behaviors influence the psychological disorders in severely burned patients. Sixty-four severely burned patients hospitalized in Guangzhou Red Cross Hospital, Guangdong Provincial Work Injury Rehabilitation Center, and Guangdong General Hospital were enrolled with cluster random sampling method. Data of their demography and situation of burns were collected. Then their coping behavior, psychological disorders including anxiety, depression and post-traumatic stress disorder (PTSD) plus its core symptoms of flashback, avoidance, and hypervigilance were assessed by medical coping modes questionnaire, self-rating anxiety scale (SAS), self-rating depression scale (SDS), PTSD checklist-civilian version (PCL-C) respectively. Correlation was analyzed between demography, burn area, coping behavior and psychological disorders. The predictive powers of educational status, burn area and coping behaviors on the psychological disorders were analyzed. The qualitative variables were assigned values. Data were processed with t test, Spearman rank correlation analysis, and multiple linear regression analysis. (1) The patients scored (19.0 ± 3.4) points in confrontation coping behavior, which showed no statistically significant difference from the domestic norm score (19.5 ± 3.8) points (t = -1.13, P > 0.05). The patients scored (16.6 ± 2.4) and (11.0 ± 2.2) points in avoidance and resignation coping behaviors, which were significantly higher than the domestic norm score (14.4 ± 3.0), (8.8 ± 3.2) points (with t values respectively 7.06 and 7.76, P values both below 0.01). The patients' standard score of SAS, SDS, PCL-C were (50 ± 11), (54 ± 11), and (38 ± 12) points. Respectively 89.1% (57/64), 60.9% (39/64), 46.9% (30/64) of the patients showed anxiety, depression, and PTSD symptoms. (2) Four independent variables: age, gender, marital status, and time after burns, were correlated with the psychological disorders

  4. Gastrointestinal flora and gastrointestinal status in children with autism -- comparisons to typical children and correlation with autism severity

    PubMed Central

    2011-01-01

    Background Children with autism have often been reported to have gastrointestinal problems that are more frequent and more severe than in children from the general population. Methods Gastrointestinal flora and gastrointestinal status were assessed from stool samples of 58 children with Autism Spectrum Disorders (ASD) and 39 healthy typical children of similar ages. Stool testing included bacterial and yeast culture tests, lysozyme, lactoferrin, secretory IgA, elastase, digestion markers, short chain fatty acids (SCFA's), pH, and blood presence. Gastrointestinal symptoms were assessed with a modified six-item GI Severity Index (6-GSI) questionnaire, and autistic symptoms were assessed with the Autism Treatment Evaluation Checklist (ATEC). Results Gastrointestinal symptoms (assessed by the 6-GSI) were strongly correlated with the severity of autism (assessed by the ATEC), (r = 0.59, p < 0.001). Children with 6-GSI scores above 3 had much higher ATEC Total scores than those with 6-GSI-scores of 3 or lower (81.5 +/- 28 vs. 49.0 +/- 21, p = 0.00002). Children with autism had much lower levels of total short chain fatty acids (-27%, p = 0.00002), including lower levels of acetate, proprionate, and valerate; this difference was greater in the children with autism taking probiotics, but also significant in those not taking probiotics. Children with autism had lower levels of species of Bifidobacter (-43%, p = 0.002) and higher levels of species of Lactobacillus (+100%, p = 0.00002), but similar levels of other bacteria and yeast using standard culture growth-based techniques. Lysozyme was somewhat lower in children with autism (-27%, p = 0.04), possibly associated with probiotic usage. Other markers of digestive function were similar in both groups. Conclusions The strong correlation of gastrointestinal symptoms with autism severity indicates that children with more severe autism are likely to have more severe gastrointestinal symptoms and vice versa. It is possible that

  5. Gastrointestinal flora and gastrointestinal status in children with autism--comparisons to typical children and correlation with autism severity.

    PubMed

    Adams, James B; Johansen, Leah J; Powell, Linda D; Quig, David; Rubin, Robert A

    2011-03-16

    Children with autism have often been reported to have gastrointestinal problems that are more frequent and more severe than in children from the general population. Gastrointestinal flora and gastrointestinal status were assessed from stool samples of 58 children with Autism Spectrum Disorders (ASD) and 39 healthy typical children of similar ages. Stool testing included bacterial and yeast culture tests, lysozyme, lactoferrin, secretory IgA, elastase, digestion markers, short chain fatty acids (SCFA's), pH, and blood presence. Gastrointestinal symptoms were assessed with a modified six-item GI Severity Index (6-GSI) questionnaire, and autistic symptoms were assessed with the Autism Treatment Evaluation Checklist (ATEC). Gastrointestinal symptoms (assessed by the 6-GSI) were strongly correlated with the severity of autism (assessed by the ATEC), (r = 0.59, p < 0.001). Children with 6-GSI scores above 3 had much higher ATEC Total scores than those with 6-GSI-scores of 3 or lower (81.5 +/- 28 vs. 49.0 +/- 21, p = 0.00002).Children with autism had much lower levels of total short chain fatty acids (-27%, p = 0.00002), including lower levels of acetate, proprionate, and valerate; this difference was greater in the children with autism taking probiotics, but also significant in those not taking probiotics. Children with autism had lower levels of species of Bifidobacter (-43%, p = 0.002) and higher levels of species of Lactobacillus (+100%, p = 0.00002), but similar levels of other bacteria and yeast using standard culture growth-based techniques. Lysozyme was somewhat lower in children with autism (-27%, p = 0.04), possibly associated with probiotic usage. Other markers of digestive function were similar in both groups. The strong correlation of gastrointestinal symptoms with autism severity indicates that children with more severe autism are likely to have more severe gastrointestinal symptoms and vice versa. It is possible that autism symptoms are exacerbated or even

  6. Early Enteral Combined with Parenteral Nutrition Treatment for Severe Traumatic Brain Injury: Effects on Immune Function, Nutritional Status and Outcomes.

    PubMed

    Fan, Mingchao; Wang, Qiaoling; Fang, Wei; Jiang, Yunxia; Li, Liandi; Sun, Peng; Wang, Zhihong

    2016-11-20

    Objective To compare the conjoint effect of enteral nutrition (EN) and parenteral nutrition (PN) with single EN or PN on immune function, nutritional status, complications and clinical outcomes of patients with severe traumatic brain injury (STBI). Methods A prospective randomized control trial was carried out from January 2009 to May 2012 in Neurological Intensive Care Unit (NICU). Patients of STBI who met the enrolment criteria (Glasgow Coma Scale score 6~8; Nutritional Risk Screening ≥3) were randomly divided into 3 groups and were admi- nistrated EN, PN or EN+PN treatments respectively. The indexes of nutritional status, immune function, complications and clinical outcomes were examined and compared statistically. Results There were 120 patients enrolled in the study, with 40 pationts in each group. In EN+PN group, T lymthocyte subsets CD3+%, CD4+%, ratio of CD3+/CD25+, ratio of CD4+/CD8+, the plasma levels of IgA, IgM, and IgG at 20 days after nutritional treatment were significantly increased compared to the baseline(t=4.32-30.00, P<0.01), and they were significantly higher than those of PN group (t=2.44-14.70; P<0.05,or P<0.01) with exception of CD4+/CD8+, higher than those of EN group (t=2.49-13.31, P<0.05, or P<0.01) with exceptions of CD3+/CD25+, CD4+/CD8+, IgG and IgM. For the nutritional status, the serum total protein, albumin, prealbumin and hemoglobin were significantly higher in the EN (t=5.87-11.91; P<0.01) and EN+PN groups (t=6.12-13.12; P<0.01) than those in PN group after nutrition treatment. The serum prealbumin was higher in EN+PN group than that in EN group (t=2.08; P<0.05). Compared to the PN group, the complication occurrence rates of EN+PN group were significantly lower in stress ulcer (22.5% vs. 47.5%; χ(2)= 8.24, P<0.01), intracranial infection (12.5% vs 32.5%;χ(2)= 6.88, P<0.01) and pyemia (25.0% vs. 47.5%; χ(2)= 6.57, P<0.05). Compared to the EN group, the complication occurrence rates of EN+PN group were significantly lower in

  7. Lung volume reduction surgery for the management of refractory dyspnea in chronic obstructive pulmonary disease.

    PubMed

    Shah, Asad A; D'Amico, Thomas A

    2009-06-01

    This review describes the role of lung volume reduction surgery (LVRS) for the management of refractory dyspnea and other debilitating conditions in patients with chronic obstructive pulmonary disease. Recent studies, including a randomized trial comparing LVRS to medical therapy, are analyzed. LVRS plus optimal medical therapy is superior to medical therapy alone in treating certain subsets of patients with severe emphysema. In patients with predominantly upper lobe emphysema and low-exercise capacity, LVRS not only improves symptoms of dyspnea and exercise intolerance, but also is associated with improved survival. Furthermore, LVRS has recently been shown to be superior to medical therapy in improving other quality of life parameters, such as nutritional status, sleep quality, and the frequency of chronic obstructive pulmonary disease (COPD) exacerbations in patients with severe emphysema. LVRS is an effective strategy in the treatment of properly selected patients with COPD, improving survival and quality of life, including exercise tolerance, dyspnea, oxygen requirement and functional status.

  8. Association of interleukin-6 gene polymorphism (rs1800796) with severity and functional status of osteoarthritis in elderly individuals.

    PubMed

    Fernandes, Marcos T P; Fernandes, Karen B P; Marquez, Audrey S; Cólus, Ilce M S; Souza, Marilesia F; Santos, João Paulo M; Poli-Frederico, Regina C

    2015-10-01

    Osteoarthritis (OA) is the most prevalent disease of the musculoskeletal system and it has an important genetic component. Despite several reports have shown the involvement of pro-inflammatory cytokine such as interleukin-1β and TNF-α, the role of interleukin-6 (IL-6) in osteoarthritis is still unclear. Thus, this study aimed to analyze the relationship between the single nucleotide polymorphism in the portion -572 of the promoter region of the IL6 gene (SNP -572G/C) with hip and knee OA in the elderly. In this case-control study, 257 physically independent elderly were recruited (case group: 92 individuals with osteoarthritis and control group: 165 individuals with no osteoarthritis). Blood samples were collected from patients for the DNA fragments extraction and amplification by real-time polymerase chain reaction (PCR) by TaqMan system for subsequent genotyping of IL6 gene. The degree of joint damage was assessed by radiographic classification based on the criteria of Kellgren and Lawrence. The functional status was evaluated by Lequesne and WOMAC questionnaires. It was observed that individuals carrying the C allele have lower susceptibility to osteoarthritis (OR=0.51, 95% CI: 0.32-0.80, p=0.004) and less radiological impairment for both hip (Fisher-Freeman-Halton test=4.2 and p=0.04) and knee joints (Fisher-Freeman-Halton test=4.7 and p=0.03). Regarding functional status, individuals carrying the C allele has a lower degree of functional impairment assessed by WOMAC (Mann-Whitney test, p=0.04), although no difference was observed in the Lequesne questionnaire (p>0.05). Additionally, it was observed a marked reduction in IL-6 serum levels in individuals with GC and CC genotypes when compared to individuals harboring GG genotype. In conclusion, the polymorphism -572G/C IL6 is a protective factor for the presence and severity of hip and knee osteoarthritis in the elderly. Further prospective studies with large sample size and methods (e.g. effect of this

  9. [Effects of glutamine-enriched enteral nutrition on nutritional status and prognosis of patients with severe head injury].

    PubMed

    Zeng, Jing; Zhao, Xiao-yu; Huang, Qiong; Wang, En-ren

    2009-10-01

    To investigate the effects of glutamine-enriched enteral nutrition on the nutritional status and prognosis of patients with severe head injury. Thirty-three patients with severe head injury were randomly divided into control group (C, 15 cases) and glutamine-enriched group (Gln, 18 cases). Patients in both groups were given routine treatment and enteral nutrition with the same amount of nitrogen and calorie. Patients in Gln group were given glutamine 0.5 g x kg(-1) x d(-1) additionally added into the nutrient fluid. Vital signs and the occurrence of side effects of all patients were observed before and after nutrition support. Venous blood and urine sample of all patients were collected before and 7, 14 days after treatment to determine the parameters of blood, urine routine and hepatorenal function. At the same time points, body mass, skin fold thickness at the region of triceps brachii (TSF), upper arm circumference (AC), upper arm muscle circumference (AMC) and fasting blood glucose of all patients were detected and determined, Glasgow coma scale (GCS) scoring was performed. The length of hospital stay of all patients was recorded. Vital signs and parameters of blood, urine routine and hepatorenal function of patients in 2 groups after nutrition treatment were close to those before treatment. Side effects, such as nausea and diarrhea occurred with spontaneous remission in a few patients. There was no statistical significant difference between 2 groups, and within each group before and after treatment, in respect of body mass and TSF (P > 0.05). Values of AC and AMC of patients in Gln group were obviously higher than those of C group (P < 0.01) on post-treatment day 14. Fasting blood glucose and GCS score of all patients before treatment were close to those on post-treatment day 14 (P > 0.05). Fasting blood glucose and GCS score of patients was respectively lower and higher in Gln group than that in C group on post-treatment day 7 (P < 0.05). Length of hospital

  10. Synthesis of refractory materials

    DOEpatents

    Holt, Joseph B.

    1984-01-01

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

  11. Synthesis of refractory materials

    DOEpatents

    Holt, J.B.

    1983-08-16

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

  12. 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.

  13. Status Epilepticus.

    PubMed

    Hocker, Sara E

    2015-10-01

    Status epilepticus, which is simultaneously a neurologic and systemic emergency, often results in significant disability and may be fatal. This article presents a pragmatic approach to the evaluation and management of status epilepticus in adults for the practicing clinician. Rapid recognition, treatment respecting a written protocol, and careful attention to potential complications may limit sequelae. Studies aimed at earlier identification of etiologies in cryptogenic status epilepticus and improving the treatment of established status epilepticus are urgently needed to limit the development of refractoriness. This article reviews the guidelines and up-to-date information on the use of both pharmacologic and nonpharmacologic therapies in status epilepticus and discusses the shifts in our understanding of the balance between the need for aggressive control of seizures and the risks of treatment. This article also presents a suggested approach to the evaluation and management of common types of status epilepticus and explores future directions.

  14. Pegloticase for treating refractory chronic gout.

    PubMed

    George, R L; Sundy, J S

    2012-07-01

    Gout is a metabolic disorder of excess uric acid accumulation that manifests clinically as inflammatory arthritis, chronic arthropathy and the formation of deposits of uric acid known as tophi. A primary objective of gout management is to reduce the excess urate burden by regular use of drugs that reduce serum urate levels. Conventional urate-lowering drugs available in the U.S. are allopurinol, febuxostat and probenecid. Some patients are intolerant to or unresponsive to urate-lowering therapies and, therefore, are said to have refractory gout. Recently, a polyethylene glycol-conjugated uricase, pegloticase, was approved for treating refractory gout. In recent clinical trials, pegloticase normalized plasma urate levels, reduced the size of tophi, and improved functional status and quality of life in patients with refractory disease. Immunogenicity to pegloticase is associated with loss of urate-lowering response and the risk of infusion reactions. Pegloticase is effective in treating hyperuricemia and the clinical manifestations of gout in patients who cannot be adequately managed with conventional therapy. Copyright 2012 Prous Science, S.A.U. or its licensors. All rights reserved.

  15. Tacrolimus Ointment for Refractory Posterior Blepharitis.

    PubMed

    Sakassegawa-Naves, Fernando Eiji; Ricci, Helena Maria Moraes; Moscovici, Bernardo Kaplan; Miyamoto, Daniela Akemi; Chiacchio, Brenda Biagio; Holzchuh, Ricardo; Santo, Ruth Muyuki; Hida, Richard Yudi

    2017-09-18

    This prospective, randomized, double-blind interventional case series was designed to evaluate the short-term efficacy of 0.03% tacrolimus ointment as a new therapeutic approach for refractory cases of posterior blepharitis. Forty eyes (20 patients) with posterior blepharitis refractory to previous treatment were randomized. Eighteen eyes (9 patients) were treated with 0.03% tacrolimus ointment and 20 eyes (10 patients) with placebo ointment twice daily. Patients were evaluated with a questionnaire and slit-lamp examination 14 days and 28 days after treatment, and symptoms and signs of blepharitis were compared to those observed at baseline. We could observe statistical difference in the outcome measurements of meibomian gland secretion, conjunctival hyperemia, telangiectasia of inferior lid, Rose Bengal, and fluorescein scoring for the study group. As for the symptoms score, we observed statistical difference in the symptoms scoring for pruritus and dry eye sensation in the tacrolimus group. This study suggests that topical administration of 0.03% tacrolimus ointment can improve some symptoms and some ocular surface status in patients with refractory posterior blepharitis.

  16. [Nutritional status in acute stage ischemic stroke and its relation to disease severity and prognosis of patients].

    PubMed

    Hong, Qing; Zhang, Li-San; Chen, Yin; He, Xu-Dong; Hu, Xing-Yue

    2015-01-01

    To investigate the nutritional status in acute stage ischemic stroke and its relation to disease severity and prognosis of patients. Fifty patients with ischemic stroke were admitted in hospital within 48 h after onset. National Institute of Health stroke scale (NIHSS) was used to assess the severity of stroke. Physical index and laboratory index were measured on d1, d7 and d14 after admission. Physical index included body weight, body mass index, triceps skin folds, upper arm circumference and arm muscle circumference. Laboratory index included prealbumin, high sensitivity C-reactive protein (hs-CRP), complement C3 and cortisol. The severity of metabolic disturbance was expressed as the difference of biochemical indexes between the d7 and d1. All cases were followed up for 6 months. The prognosis of stroke was evaluated with modified Rankin (mRankin) scores. No significant changes of physical indexes were found between d7 and d1. The levels of prealbumin and complement C3 on d7 after admission were significantly decreased compared to d1 (198.8 mg/L±20.3 mg/L vs 286.7 mg/L±23.8 mg/L and 0.6 g/L±0.1 g/L vs 1.0 g/L±0.1 g/L, respectively, both P<0.05). The levels of hs-CRP and cortisol at d7 were significantly increased compared to d1 (495.2 nmol/L±39.5 nmol/L vs 24.1 mg/L±5.2 mg/L and 396.4 nmol/L±41.3 nmol/L vs 5.1 mg/L±1.2 mg/L, respectively, both P<0.05). On d14 after admission hs-CRP (13.2 mg/L±4.5 mg/L) and cortisol levels (463.4 nmol/L±32.1 nmol/L) were still significantly higher than d1 (both P<0.05). However, there were no difference in prealbumin (259.2 mg/L±22.8 mg/L) and complement C3 (0.8 g/L±0.2 g/L) levels between d1 and d14 after admission. Correlation analysis revealed that the NIHSS scores and mRankin scores were correlated with nutrition metabolism disturbances (P<0.05). Nutrition metabolism disturbances in patients with acute ischemic stroke are related to the disease duration, the severity and prognosis of stroke.

  17. Stochastic histories of refractory interstellar dust

    NASA Technical Reports Server (NTRS)

    Liffman, Kurt; Clayton, Donald D.

    1988-01-01

    Histories of refractory interstellar dust particles (IDPs) are calculated. The profile of a particle population is assembled from a large number of stochastic, or Monte Carlo, histories of single particles; the probabilities for each of the events that may befall a given particle are specified, and the particle's history is unfolded by a sequence of random numbers. The assumptions that are made and the techniques of the calculation are described together with the results obtained. Several technical demonstrations are presented.

  18. Stochastic histories of refractory interstellar dust

    NASA Technical Reports Server (NTRS)

    Liffman, Kurt; Clayton, Donald D.

    1988-01-01

    Histories of refractory interstellar dust particles (IDPs) are calculated. The profile of a particle population is assembled from a large number of stochastic, or Monte Carlo, histories of single particles; the probabilities for each of the events that may befall a given particle are specified, and the particle's history is unfolded by a sequence of random numbers. The assumptions that are made and the techniques of the calculation are described together with the results obtained. Several technical demonstrations are presented.

  19. Guillain-Barré Syndrome Presenting with Sinus Node Dysfunction and Refractory Shock

    PubMed Central

    Ha, Le Dung; Abbas, Farrukh; Rao, Mohan

    2017-01-01

    Patient: Male, 76 Final Diagnosis: Guillain-Barré syndrome Symptoms: Bradycardia • refractory hypotension Medication: — Clinical Procedure: — Specialty: Cardiology Objective: Unusual clinical course Background: Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyneuropathy that is usually associated with preceding respiratory or gastrointestinal infection and has the hallmark manifestation of ascending flaccid paralysis. We report an atypical presentation of GBS. Case Report: A 76-year-old male presented with acute onset of diaphoresis and altered mental status. He subsequently developed severe bradycardia and refractory hypotension, which initially responded to dopamine infusion. A temporary pacemaker wire was placed to stabilize the heart rate but hypotension persisted. Acute autonomic dysfunction was suspected. Head and chest imaging was unrevealing. Lumbar puncture revealed albuminocytologic dissociation that was consistent with a diagnosis of GBS. Hospital course was complicated with acute kidney injury and metabolic acidosis. Plasmapharesis was initiated. The patient eventually died of multi-organ failure. Conclusions: Autonomic dysfunction is a known but rare presentation of GBS. In patients presenting with refractory bradycardia and hypotension, GBS should be considered in the differential diagnosis. PMID:28283677

  20. The geochemical behavior of refractory noble metals and lithophile trace elements in refractory inclusions in carbonaceous chondrites

    NASA Technical Reports Server (NTRS)

    Fegley, B., Jr.; Kornacki, A. S.

    1984-01-01

    Recent models of Ca, Al-rich (CAI) inclusion petrogenesis, and the recent availability of thermodynamic data have led to the reexamination of the geochemical behavior of the refractory noble metals (RNM) and several lithophile refractory trace elements in CAI's in the context of distillation models. Here, pertinent chemical and mineralogical properties of the various classes of refractory inclusions are reviewed, and calculations of the stability of LRTE-RNM alloys and several LRTE oxides under nebular conditions are presented. The calculations, observations and experimental results are applied to a new model of the origin of refractory metal nuggets, and a specific mechanism is identified for producing Group II chemical patterns in a cold star nebula by fractionating interstellar dust at low temperature on the basis of physical differences between different populations of pre-solar grains.

  1. 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.

  2. Refractory ascites in the chronic myeloproliferative syndrome: A case report

    SciTech Connect

    Jacobs, P.; Wood, L.; Robson, S. )

    1991-06-01

    In a patient with myelofibrosis, tense ascites refractory to conventional therapy resulted from extensive seeding of the peritoneum with colonies of extramedullary haematopoiesis. Whole abdominal radiation was found to be effective and well tolerated, and brought about prompt and lasting resorption of the exudate, with weight reduction and improvement in performance status from 50% to 90% on the Karnofsky rating.

  3. Approaches to refractory epilepsy

    PubMed Central

    Engel, Jerome

    2014-01-01

    Epilepsy is one of the most common serious neurological conditions, and 30 to 40% of people with epilepsy have seizures that are not controlled by medication. Patients are considered to have refractory epilepsy if disabling seizures continue despite appropriate trials of two antiseizure drugs, either alone or in combination. At this point, patients should be referred to multidisciplinary epilepsy centers that perform specialized diagnostic testing to first determine whether they are, in fact, pharmacoresistant, and then, if so, offer alternative treatments. Apparent pharmacoresistance can result from a variety of situations, including noncompliance, seizures that are not epileptic, misdiagnosis of the seizure type or epilepsy syndrome, inappropriate use of medication, and lifestyle issues. For patients who are pharmacoresistant, surgical treatment offers the best opportunity for complete freedom from seizures. Surgically remediable epilepsy syndromes have been identified, but patients with more complicated epilepsy can also benefit from surgical treatment and require more specialized evaluation, including intracranial EEG monitoring. For patients who are not surgical candidates, or who are unwilling to consider surgery, a variety of other alternative treatments can be considered, including peripheral or central neurostimulation, ketogenic diet, and complementary and alternative approaches. When such alternative treatments are not appropriate or effective, quality of life can still be greatly improved by the psychological and social support services offered by multidisciplinary epilepsy centers. A major obstacle remains the fact that only a small proportion of patients with refractory epilepsy are referred for expert evaluation and treatment. PMID:24791078

  4. Refractory giardiasis in Spanish travellers.

    PubMed

    Muñoz Gutiérrez, Jose; Aldasoro, Edelweiss; Requena, Ana; Comin, Ana M; Pinazo, Maria Jesús; Bardají, Azucena; Oliveira, Inés; Valls, Maria Eugenia; Gascon, Joaquim

    2013-01-01

    Drug failure is a common cause of symptom persistence after treatment of imported Giardia duodenalis. In this retrospective study we describe a high prevalence of refractory giardiasis in people attended in a travel clinic in Spain, especially those with infections acquired in Asia. Moreover, we discuss various treatment strategies to tackle G. duodenalis that is refractory to nitroimidazoles.

  5. 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.

  6. The ketogenic diet for the treatment of pediatric status epilepticus.

    PubMed

    O'Connor, Sunila E; Ream, Margie A; Richardson, Candy; Mikati, Mohamad A; Trescher, Willam H; Byler, Debra L; Sather, Joan D; Michael, Elizabeth H; Urbanik, Kelly B; Richards, Jennifer L; Davis, Ronald; Zupanc, Mary L; Zupec-Kania, Beth

    2014-01-01

    Refractory status epilepticus carries a high risk of morbidity and mortality for children. Traditional treatment of status epilepticus consists of multiple anticonvulsant drugs and, if needed, induction of a medical coma. The ketogenic diet has been used for intractable epilepsy for many years. The purpose of this article is to report a case series of five patients with refractory status epilepticus successfully managed with the ketogenic diet. A summary of pediatric patients with refractory status epilepticus treated with diet was performed. Ketogenic diet therapy should be considered as a treatment option in pediatric patients with refractory status epilepticus. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Biopterin status in dogs with myxomatous mitral valve disease is associated with disease severity and cardiovascular risk factors.

    PubMed

    Reimann, M J; Häggström, J; Mortensen, A; Lykkesfeldt, J; Møller, J E; Falk, T; Olsen, L H

    2014-01-01

    Endothelial dysfunction (ED) has been suggested to be associated with myxomatous mitral valve disease (MMVD) in dogs. Tetrahydrobiopterin (BH4) is an important cofactor for production of the endothelium-derived vasodilator nitric oxide (NO). Under conditions of oxidative stress, BH4 is oxidized to the biologically inactive form dihydrobiopterin (BH2). Thus, plasma concentrations of BH2 and BH4 may reflect ED and oxidative stress. To determine plasma concentrations of BH2 and BH4 in dogs with different degrees of MMVD. Eighty-four privately owned dogs grouped according to ACVIM guidelines (37 healthy control dogs including 13 Beagles and 24 Cavalier King Charles Spaniels [CKCSs], 33 CKCSs with MMVD of differing severity including 18 CKCSs [group B1] and 15 CKCSs [group B2], and 14 dogs of different breeds with clinical signs of congestive heart failure [CHF] because of MMVD [group C]). Dogs underwent clinical examination including echocardiography. Plasma concentrations of BH2 and BH4 were measured using high-performance liquid chromatography with fluorescence detection. Higher plasma BH4 and BH2 concentrations were found with dogs in CHF compared with all other groups (control, B1 and B2; P ≤ .001). Females had higher concentrations of BH4 and BH4/BH2 (P ≤ .0003). BH4/BH2 was found to decrease with age (P < .0001). Cardiovascular risk factors in humans such as passive smoking (P ≤ .01) and increased body weight (P ≤ .009) were associated with lower BH4 concentrations. Age, sex, body weight, passive smoking, and cardiac status are associated with plasma biopterin concentration in dogs. Additional studies should clarify the clinical implications of the findings. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  8. Ciclosporin and refractory colitis.

    PubMed

    Hawthorne, A Barney

    2003-03-01

    Intravenous ciclosporin 4 mg/kg daily is rapidly effective as a salvage therapy for patients with refractory colitis, who would otherwise face colectomy, but its use is controversial because of risk of toxicity, and long-term failure rate. Opportunistic infections remain a serious concern, with a number of reports of death related to ciclosporin. Renal and neurotoxicity are also well-recognized. The drug should not be continued for more than 3-6 months and its main role is as a bridge to azathioprine or 6-mercaptopurine. Risks of toxicity can be reduced by using lower doses (2 mg/kg/day intravenously), by oral microemulsion ciclosporin, or by monotherapy without corticosteroids. Preliminary evidence shows good response rates, but further studies are needed to confirm optimal use of this potent, but hazardous, therapy.

  9. Refractory gastroesophageal reflux disease

    PubMed Central

    Subramanian, Charumathi Raghu; Triadafilopoulos, George

    2015-01-01

    Gastroesophageal reflux disease (GERD) is a condition that develops when the reflux of stomach contents into the esophagus causes troublesome symptoms, esophageal injury, and/or complications. Use of proton pump inhibitors (PPI) remains the standard therapy for GERD and is effective in most patients. Those whose symptoms are refractory to PPIs should be evaluated further and other treatment options should be considered, according to individual patient characteristics. Response to PPIs could be total (no symptoms), partial (residual breakthrough symptoms), or absent (no change in symptoms). Patients experiencing complete response do not usually need further management. Patients with partial response can be treated surgically or by using emerging endoscopic therapies. Patients who exhibit no response to PPI need further evaluation to rule out other causes. PMID:25274499

  10. Treatment of relapsed and refractory multiple myeloma.

    PubMed

    Singhal, Seema; Mehta, Jayesh

    2003-06-01

    The definition of relapsed and refractory myeloma was straightforward when melphalan-prednisone constituted the mainstay of treatment and high-dose therapy with transplantation was rarely used in myeloma. However, several advances have occurred in the treatment of myeloma over the past decade. Most notably, high-dose therapy and transplantation have become broadly applicable, thalidomide has become available as effective salvage therapy, and several investigational agents with novel mechanisms of action appear to be very promising. Because of the differing properties of some of these agents, it is often possible to control the disease with an alternative treatment approach after the failure of one therapy. Some data indicate that combinations of these agents work when the drugs have failed individually. Therefore, refractory myeloma indicates disease unresponsive to the most recent therapy administered. Broadly, the salvage approaches that are used in patients with refractory or relapsed disease include high-dose dexamethasone, high-dose chemotherapy with autotransplantation, allogeneic hematopoietic stem cell transplantation, thalidomide-based therapies, and novel/investigational agents. The appropriate therapy for a given situation depends on the nature of the disease, age, organ function, bone marrow function, prior treatment, the availability of stem cell donors, and access to novel agents. A therapeutic trial of thalidomide is essential at some stage of the disease in all patients. High-dose therapy with autotransplantation is needed at some stage of the disease in most patients younger than 65 to 70 years.

  11. Chronic lymphocytic leukemia: treatment options for patients with refractory disease.

    PubMed

    Motta, Marina; Wierda, William G; Ferrajoli, Alessandra

    2009-09-01

    Patients with purine analogue-refractory chronic lymphocytic leukemia (CLL) have short survival and limited treatment options. Defining the best salvage strategies for this population is challenging, because limited data are available from clinical trials, and because studies have enrolled mixed populations (patients with recurrent and refractory disease or patients with refractory disease and Richter transformation). Moreover, patients with refractory CLL have a high incidence of unfavorable molecular and clinical features, such as high-risk genomic profiles, unmutated immunoglobulin heavy-chain genes, expression of zeta-chain-associated protein kinase 70, and bulky lymphadenopathies. These patients are also severely immunosuppressed because of the underlying disease and the treatments received, and experience a high rate of infectious complications that pose an additional difficulty in selecting treatment. Despite these challenges, in parallel with better characterizations of the biologic features of refractory CLL, the number of available treatment modalities for this population has increased. Several chemoimmunotherapy combinations have been developed, and novel agents with a different mechanism of action are being investigated in clinical trials. Furthermore, allogeneic stem cell transplantation with nonmyeloablative conditioning regimens is a therapeutic strategy that is increasing