Early efficacy trial of anakinra in corticosteroid-resistant autoimmune inner ear disease

BACKGROUND. Autoimmune inner ear disease (AIED) is a rare disease that results in progressive sensorineural hearing loss. Patients with AIED initially respond to corticosteroids; however, many patients become unresponsive to this treatment over time, and there is no effective alternative therapy for these individuals. METHODS. We performed a phase I/II open-label, single-arm clinical trial of the IL-1 receptor antagonist anakinra in corticosteroid-resistant AIED patients. Given that the etiology of corticosteroid resistance is likely heterogeneous, we used a Simon 2-stage design to distinguish between an unacceptable (= 30%) response rate to anakinra therapy. Subjects received 100 mg anakinra by subcutaneous injection for 84 days, followed by a 180-day observational period. RESULTS. Based on patient responses, the Simon 2-stage rule permitted premature termination of the trial after 10 subjects completed the 84-day drug period, as the target efficacy for the entire trial had been achieved. Of these 10 patients, 7 demonstrated audiometric improvement, as assessed by pure tone average (PTA) and word recognition score (WRS). In these 7 responders, reduced IL-1 beta plasma levels correlated with clinical response. Upon discontinuation of treatment, 3 subjects relapsed, which correlated with increased IL-1 beta plasma levels. CONCLUSION. We demonstrated that IL-1 beta inhibition in corticosteroid-resistant AIED patients was effective in a small cohort of patients and that IL-1 beta plasma levels associated with both clinical hearing response and disease relapse. These results suggest that a larger phase II randomized clinical trial of IL-1 beta inhibition is warranted

Control of kinetic changes in ATPase activity of soluble coupling factor 1 from chloroplasts

This repository item contains a single issue of The ISCIP Analyst, an analytical review journal published from 1996 to 2010 by the Boston University Institute for the Study of Conflict, Ideology, and Policy

Properties of the cyanobacterial coupling factor ATPase from Spirulina platensis : II. Activity of the purified and membrane-bound enzymes

Cyanobacterial (Spirulina platensis) photosynthetic membranes and isolated F1 ATPase were characterized with respect to ATP activity. The following results indicate that the regulation of expression of ATPase activity in Spirulina platensis is similar to that found in chloroplasts: (a) the ATPase activity of Spirulina membranes and isolated F1 ATPase is mostly latent, a characteristic of chloroplast ATPase activity; (b) treatments that elicit ATPase activity in higher plant chloroplast thylakoids and isolated chloroplast coupling factor (CF1) greatly stimulate the activity of Spirulina membranes and F1, and (c) the cation specificity of chloroplast ATPase activity, e.g., light-induced membrane activity that is magnesium dependent and trypsin-activated CF1 activity that is calcium dependent, is also observed in Spirulina. Thus, an 8- to 15-fold increase in specific activity (to 13-15 [mu]mol Pi min-1 mg chl-1) is obtained when Spirulina membranes are treated with trypsin (CaATPase) or with methanol (MgATPase); a light induced, dithiothreitol-dependent MgATPase activity is also found in the membranes. Purified Spirulina F1 is a CaATPase when activated with trypsin (endogenous activity increases from 4 to 27-37 [mu]mol Pi min-1 mg protein-1) or with dithiothreitol (5.6 [mu]mol Pi min-1 mg-1), but a MgATPase when assayed with methanol (18-20 [mu]mol Pi min-1 mg-1). The effects of varying calcium and ATP concentrations on the kinetics of trypsin-induced CaATPase activity of Spirulina F1 were examined. When the calcium concentration is varied at constant ATP concentration, the velocity plot shows a marked sigmoidicity. By varying Ca-ATP metal-nucleotide complex concentration at constant concentrations of free calcium or ATP, it is shown that the sigmoidicity is due to the effect of free ATP, which changes the Hill constant to 1.6 from 1.0 observed when the free calcium concentration is kept constant at 5 m. Therefore not only is ATP an inhibitor but it is also an allosteric effector of Spirulina F1 ATPase activity. At 5 m free calcium, the Km for the Ca-ATP metal-nucleotide complex is 0.42 m.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26258/1/0000339.pd

Alternate Splicing of Interleukin-1 Receptor Type II (IL1R2) In Vitro Correlates with Clinical Glucocorticoid Responsiveness in Patients with AIED

Autoimmune Inner Ear Disease (AIED) is poorly characterized clinically, with no definitive laboratory test. All patients suspected of having AIED are given glucocorticoids during periods of acute hearing loss, however, only half initially respond, and still fewer respond over time

Medical and Audiological Indications for Implantable Auditory Devices

© 2018 Elsevier Inc. Implantable auditory devices (IADs) are a viable hearing restoration option for patients with hearing loss. Conditions such as chronic otitis externa, congenital aural atresia, and chronic otitis media can be treated with a variety of implants. Progressive disease are also amenable to restoration with IADs, providing stabilized hearing. When considering the best rehabilitative options, the patient\u27s preference, ease of surgery, ease of device use, quality of life, and the traditional alternatives (such as ossiculoplasty, hearing aids, and cochlear implants) need to be considered. Patients with conductive, mixed, and sensorineural losses, mild to severe in nature, can be candidates for IADs