Trial of dextromethorphan/quinidine to treat levodopa‐induced dyskinesia in Parkinson's disease

Background : Nondopaminergic pathways represent potential targets to treat levodopa‐induced dyskinesia in Parkinson's disease (PD). This pilot‐study (NCT01767129) examined the safety/efficacy of the sigma‐1 receptor‐agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa‐induced dyskinesia. Methods : PD patients were randomized to dextromethorphan/quinidine (45 mg/10 mg twice daily)/placebo in two 2‐week double‐blind, crossover treatment periods, with intervening 2‐week washout. After 14 days, a 2‐hour intravenous levodopa‐infusion was administered. Patient examinations were videotaped before infusion (“off” state) and every 30 minutes during and afterwards until patients returned to “off.” The primary endpoint was dyskinesia‐severity during infusion measured by Unified Dyskinesia Rating Scale part 3 area‐under‐curve scores (blinded expert rated). Additional endpoints included other dyskinesia/motor assessments, global measures of clinical‐change, and adverse‐events. Results : A total of 13 patients were randomized and completed the study (efficacy‐evaluable population). Dyskinesia‐severity was nonsignificantly lower with dextromethorphan/quinidine than placebo during infusion (area‐under‐curve 966.5 vs 1048.8; P = .191 [efficacy‐evaluable patients]), and significantly lower in a post‐hoc sensitivity analysis of the per‐protocol‐population (efficacy‐evaluable patients with ≥ 80% study‐drug‐compliance, n = 12) when measured from infusion start to 4‐hours post–infusion completion (area‐under‐curve 1585.0 vs 1911.3; P = .024). Mean peak dyskinesia decreased significantly from infusion‐start to return to “off” (13.3 vs 14.9; P = .018 [efficacy‐evaluable patients]). A total of 9 patients rated dyskinesia “much/very much improved” on dextromethorphan/quinidine versus 1‐patient on placebo. Dextromethorphan/quinidine did not worsen PD‐motor scores, was generally well tolerated, and was associated with more frequent adverse events. Conclusion : This study provides preliminary evidence of clinical benefit with dextromethorphan/quinidine for treating levodopa‐induced dyskinesia in PD. Larger studies with a longer treatment duration need to corroborate these early findings. © 2017 International Parkinson and Movement Disorder Society     

Inflammation and the Aging Process: Devil or Angel

Inflammation is often viewed as a pathologic mechanism leading to tissue damage and interference with function, such as the process of chronic tissue scarring or fibrosis. However, it is important to note that inflammation is a crucial component of normal tissue repair as well as being fundamental to the body's defense against infection. Considering inflammation as a "causative agent in aging" belies the underlying mechanisms whereby the acute inflammatory response is necessary for survival, and efforts to reduce and control the inflammatory response leave the host susceptible to infectious agents and improper healing. Chronic inflammation inevitably has initiating mechanisms that include immune, autoimmune, and metabolic pathways, leading to the activation and presence of the host-protective response. It is more appropriate to target the underlying initiating conditions than the inflammatory process that ensues and treat the basic mechanisms of disease rather than interfere in a very important protective mechanism of the host.     

Dental materials: 1979 literature review Part II

This paper, which is presented in two parts, reviews the work on dental materials published in 1979. Included in Part II are sections on impression materials, model, die and investment materials, waxes, acrylic resins, denture base polymers, soft lining materials and tissue conditioners, cast and wrought dental alloys, ceramics, implants and, finally, corrosion. Part I included sections on dental biomechanics, fissure sealants, cements, amalgam, composite filling materials, endodontic materials and microleakage.     

Aspects of the chemistry of polysulphide impression material

The composition, structure and setting reactions of polysulphide impression materials are reviewed in order to correct errors of fact and misinterpretations. A model for molecular size distribution is used to clarify the composition of the prepolymer and the process of setting.     

Effect of humidity on calcium sulphate hemihydrate

The conversion of calcium sulphate hemihydrate powders to dihydrate by reaction with atmospheric water vapour has been re-examined gravimetrically. Storage is usually said to be safe at less than '70 per cent RH', but this is shown to be an inadequate criterion (water vapour pressure being more useful in the context) and based on an inappropriate experiment. At 23 degrees C, greater than about 2.3 kPa water vapour pressure caused rapid reaction, and this may be taken as a more reliable critical value.     

Development of Noncarious Cervical Notch Lesions in Vitro

Abstract: Purpose : The initiation and progression of noncarious cervical notch lesions (NCCL) continues to perplex clinicians worldwide and poses a considerable restorative challenge. The purpose of this brief communication is to report what is believed to be the first in vitro production of notch-shaped lesions in the cervical third of premolar teeth.
Materials and Methods : The lesions, were produced by axial loading of selected permanent premolar teeth in a 10% aqueous solution of sulfuric acid over a period of 5 days, followed by immersion in water for 7 days.
Results : Results revealed macroscopic and microscopic features similar to those observed in noncarious cervical lesions in vivo. The lesions were incidental findings while the authors were studying stress corrosion of enamel at low pH. Although much remains to be investigated regarding the etiology and pathogenesis of NCCL, axial loading and a corrosive environment may be implicated in these processes. The artificial lesions arose in clinically sound teeth, suggesting that there is no simple clinical examination to identify teeth at risk from NCCL.