Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis

Objectives: To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity.Methods: In this 20-week, randomized, double-blind, placebo-controlled phase 1b dose-escalation trial (registration number NCT01517282), adults with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) received an IV infusion of placebo (n = 6) or MOR103 0.5 (n = 8), 1.0 (n = 8), or 2.0 (n = 9) mg/kg every 2 weeks for 10 weeks. Patients had to have ≤10 gadolinium (Gd)-enhancing brain lesions on T1-weighted MRI at baseline. The primary objective was safety.Results: Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. The most frequent was nasopharyngitis. Between-group differences in TEAE numbers were small. There were no TEAE-related trial discontinuations, infusion-related reactions, or deaths. Nine patients experienced MS exacerbations: 3, 5, 1, and 0 patient(s) in the placebo, 0.5, 1.0, and 2.0 mg/kg groups, respectively. A few T1 Gd-enhancing lesions and/or new or enlarging T2 lesions indicative of inflammation were observed in all treatment groups. No clinically significant changes were observed in other clinical assessments or laboratory safety assessments. No anti-MOR103 antibodies were detected. PK evaluations indicated dose linearity with low/no drug accumulation over time.Conclusions: MOR103 was generally well-tolerated in patients with RRMS or SPMS. No evidence of immunogenicity was found.Classification of evidence: This phase 1b study provides Class I evidence that MOR103 has acceptable tolerability in patients with MS

Topiramate in the Treatment of Myoclonic-Astatic Epilepsy in Children: A Retrospective Hospital Audit

BACKGROUND: Myoclonic-Astatic Epilepsy (MAE) usually starts before five years of age and is associated with very frequent seizures and is highly resistant to treatment. AIM: To investigate the outcome of adjunctive topiramate (TPM) therapy in children with a diagnosis of MAE syndrome. Subjects AND METHODS: In an outpatient setting, case notes of 27 children who received TPM were retrieved and analysed. RESULTS: Records of 6 children with MAE, who were experiencing 2-8 atonic seizures daily before starting TPM were studied. Improvement was noted after addition of TPM (mean dose at steady-state 7.4\ub12.5mg/kg/day) to the regimen of 1-3 anti-epileptic drugs they were receiving concurrently. All but one child improved following the titration period: one had 50-80% improvement in the frequency of atonic seizures and three had over 80% improvement. However, one child who showed over 80% improvement and was free of atonic seizures, later developed increased frequency of other seizure types. In one child there was no significant improvement. Improvement has been sustained for over 6 months in three patients and over 4 months in one; three have continued TPM. TPM was stopped in three patients (reduction in seizure control/no improvement). CONCLUSIONS: This study supports the efficacy of TPM in controlling atonic seizures in MAE and indicates that it should be considered as an add-on drug in the management of this 'difficult-to-treat' epileptic syndrome

Topiramate in the treatment of Myoclonic-Astatic Epilepsy in children: a retrospective hospital audit

BACKGROUND: Myoclonic-Astatic Epilepsy (MAE) usually starts before five years of age and is associated with very frequent seizures and is highly resistant to treatment. AIM: To investigate the outcome of adjunctive topiramate (TPM) therapy in children with a diagnosis of MAE syndrome. Subjects AND METHODS: In an outpatient setting, case notes of 27 children who received TPM were retrieved and analysed. RESULTS: Records of 6 children with MAE, who were experiencing 2-8 atonic seizures daily before starting TPM were studied. Improvement was noted after addition of TPM (mean dose at steady-state 7.4±2.5mg/kg/day) to the regimen of 1-3 anti-epileptic drugs they were receiving concurrently. All but one child improved following the titration period: one had 50-80% improvement in the frequency of atonic seizures and three had over 80% improvement. However, one child who showed over 80% improvement and was free of atonic seizures, later developed increased frequency of other seizure types. In one child there was no significant improvement. Improvement has been sustained for over 6 months in three patients and over 4 months in one; three have continued TPM. TPM was stopped in three patients (reduction in seizure control/no improvement). CONCLUSIONS: This study supports the efficacy of TPM in controlling atonic seizures in MAE and indicates that it should be considered as an add-on drug in the management of this 'difficult-to-treat' epileptic syndrome

Short contact time CH4 partial oxidation over Ni based catalyst at 1.5MPa

Gas-to-liquid technologies to produce Fischer\u2013Tropsch fuels are economically sustainable at very large scales\u2014 30\u2008000bbld 121. To achieve a viable process at a scale less than 100bbld 121 requires a compact design, like a short contact time reactor and mass manufacturing to reduce capital cost. We tested the activity of 2.25%Ni/0.1%Ru/CeO2 supported on FeCrAl gauze (Ni2510) to partially oxide methane at a contact time less than 0.050s. Besides, the very short contact time, an additional feature of this work is that the catalyst activated on-stream without a hydrogen pretreatment step. The reactor operated at 1.5MPa, 800\ub0C\ua0to\ua0950\ub0C, and a CH4/O2 ratio varying from 1.6 to 1.8 v/v. Methane partially oxidized carbon monoxide (direct mechanism) rather than combusting to CO2 followed by steam reforming to CO (indirect mechanism). The following phenomena support the direct mechanism hypothesis: (i) the selectivity improved when reducing residence time, (ii) the mass spectrometer detected both O2 and CO at the effluent (simultaneously), (iii) metallic Ni clusters on the Ni2510 were absent under reaction conditions based on in situ X-ray absorption spectroscopy. Loading Ni/Al2O3 powder downstream of the Ni2510 increased syngas yield, as this catalyst promoted steam and dry reforming. Soot forms upstream of the Ni2510 catalyst via a retro-propagation mechanism in which methyl radicals produced on the catalyst surface react with the incoming feed gas

La guardia notturna : operetta in 3 atti /

Performers' names not given.Librettist unknown.Preface--p. 3.UNC Italian Opera Libretto Collection.At head of title: Compagnia italiana d'operette comiche Luigi Maresca.Also known as: La guardia notturna di Dresda--Melodramma italiano 1861-1900.Mode of access: Internet