Dupilumab therapy for patients with refractory eosinophilic otitis media associated with bronchial asthma

ObjectivesEosinophilic otitis media (EOM) is an intractable otitis media mostly associated with bronchial asthma. Dupilumab, an anti-interleukin (IL)-4 receptor (R)α, is effective and has been approved for use in patients with moderate to severe bronchial asthma, atopic dermatitis and chronic rhinosinusitis with nasal polyposis, whose diseases are not controlled by previous treatments including other molecular targeted drugs. We aimed to assess efficacy of dupilumab in three EOM patients with associated bronchial asthma, who were poor responders to previous topical and systemic corticosteroid therapy and molecular targeted therapies.Patients and methodsThree patients with severe, refractory EOM (two with a granulation type) associated with bronchial asthma received dupilumab as add-on therapy for at least 6 months. The efficacy of dupilumab therapy was evaluated using severity scores, symptom scores, hearing acuities, temporal bone computed tomography (CT) scores, and surrogate markers before and after therapy.ResultsSeverity scores in all patients were dramatically reduced to 2 points or less (full score: 16 points) after initiation of therapy. Air conduction hearing levels were improved in all patients. Temporal bone CT scores in two patients were reduced, and serum IgE levels in all three patients also decreased following therapy.ConclusionWe provide the first report that add-on dupilumab therapy was effective in patients with severe, refractory EOM who did not respond to the treatments including other molecular targeted therapy. Patients with severe middle ear mucosal change may benefit particularly from dupilumab therapy.     

Neuropeptide Y modulates membrane excitability in neonatal rat mesencephalic V neurons

Neuropeptide Y (NPY) is one of a number of neuropeptides with powerful orexigenic effects. Intracerebroventricular administration of NPY induces increases in food intake and alters feeding rate. Besides it role in feeding behavior, NPY also has significant effects on neuronal systems related to other spontaneous behaviors such as rearing and grooming. In the present study, we examined the direct effects of NPY on mesencephalic V neurons (Mes V), which are important sensory neurons involved in oral motor reflexes and rhythmical jaw movements, as well as masticatory proprioception. Coronal brain slices were prepared from neonatal Sprague-Dawley rats (P3-17) and whole-cell patch clamp recordings were obtained from Mes V neurons. Bath application of NPY depolarized the membrane potential and induced inward current in most neurons. Application of NPY shortened the duration of the afterhyperpolarization following an action potential, and increased the mean spike frequency during repetitive discharge. In those neurons which exhibited rhythmical burst discharge in response to maintained current injection, the bursting frequency was also increased. These effects were mediated predominately by both Y1 and Y5 receptors.     

Gradients in periodontal status in Japanese employed males

AIM: The objective was to assess whether there was a social gradient in periodontal status by job classification in Japanese male workers. MATERIAL AND METHODS: Study participants were 15,803 Japanese male workers aged 20-69 years. There were seven groups classified by jobs. Oral examinations were conducted using community periodontal index (CPI). RESULTS: The percentages of sextants with a CPI score of 3 or 4 of professionals were significantly lower than for other job classes. The gradient also existed for the percentage of sextants with CPI score 4. After adjusting for age, a history of diabetes mellitus and smoking status, those lower on the gradient, namely, drivers, service occupations, salespersons and managers were 2.0, 1.5, 1.4 and 1.4, times, respectively more likely to have one or more sextants with CPI score 3 or 4 compared with professionals. Odds ratios of having more than one or more sextants with CPI score 4 after adjusting for age, clinical history of diabetes mellitus and smoking status for drivers, service occupations, salespersons and managers were 2.1, 1.5, 1.5 and 1.2, respectively, compared with professionals. CONCLUSIONS: There was a gradient in periodontal status by job classification. Professional and office workers had better periodontal status than salespersons, service occupations and drivers.     

Site specific mineral composition and microstructure of human supra-gingival dental calculus

Dental calculus has been implicated in the aetiology of several periodontal conditions. Its prevention and removal are therefore desirable clinical goals. While it is known that calculus is very variable in chemical composition, crystallinity and crystallite size little is known about site specific variability within a dentition and between individuals. With this in mind, a study was undertaken to investigate the comparative site specific nature and composition of human dental supra-gingival dental calculus obtained from 66 male patients visiting for their dental check-up using fluorescent X-ray spectroscopy, X-ray diffractometry and Fourier transform infrared spectroscopy. The supra-gingival dental calculus formed on the lingual surfaces of lower anterior teeth and the buccal surfaces of upper molar teeth were classified into four types based on calcium phosphate phases present. There was significant difference in composition of the crystal phase types between lower and upper teeth (p<0.01). There was no significant difference in crystal size between dental calculus on anterior or molar teeth of all samples. The degree of crystallinity of dental calculus formed on the upper molar teeth was higher than that formed on the lower anterior teeth (p<0.01). The CO(3)(2-) contents in dental calculus formed on the lower anterior teeth were higher than on upper molar teeth (p<0.05) which might explain the difference in crystallinity. Magnesium and Si contents and Ca:P ratio on the other hand showed no significant difference between lower and upper teeth. It was concluded that the crystal phases, crystallinity and CO(3)(2-) contents of human dental supra-gingival dental calculus is related to its location in the mouth.     

Ubiquitin‐negative,eosinophilic neuronal cytoplasmic inclusions associated with stress granules and autophagy: An immunohistochemical investigation of two cases

Identification of the proteinaceous components of the pathological inclusions is an important step in understanding the associated disease mechanisms. We immunohistochemically examined two previously reported cases with eosinophilic neuronal cytoplasmic inclusions (NCIs) (case 1, Mori et al. Neuropathology 2010; 30: 648–53; case 2, Kojima et al. Acta Pathol Jpn 1990; 40: 785–91) using 67 antibodies against proteins related to cytoskeletal constituents, ubiquitin‐proteasome system, autophagy‐lysosome pathway and stress granule formation. Regional distribution pattern of eosinophilic NCIs in case 1 was substantially different from that in case 2. However, NCIs in both cases were immunonegative for ubiquitin and p62 and were immunopositive for stress granule markers as well as autophagy‐related proteins, including valosin‐containing protein. Considering that eukaryotic stress granules are cleared by autophagy and valosin‐containing protein function, our findings suggest that eosinophilic NCIs in the present two cases may represent the process of autophagic clearance of stress granules.     

Hypercapnic acidosis minimizes endotoxin-induced gut mucosal injury in rabbits

Objective  Recent evidence demonstrated that hypercapnic acidosis due to lung protective strategy was not only permissive but also even therapeutic for injured lung. Since the effects of hypercapnic acidosis on extra-pulmonary organs remain to be clarified, we tested the hypothesis that hypercapnic acidosis protects gut mucosal barrier function by modulating inflammation in a rabbit model of endotoxemia. Design  Prospective randomized animal study. Setting  University research laboratory. Subjects  Male New Zealand white rabbits. Interventions  Thirty-two animals were randomly allocated into two groups: normocapnia (n = 17) and hypercapnia (n = 15). The latter group received F_ICO₂ 5% under mechanical ventilation to achieve hypercapnia throughout the study periods, whereas the former with F_ICO₂ 0%. Measurements and results  Arterial blood gas, intramucosal pH (pHi) and portal blood flow were assessed at baseline, 2-h and 4-h infusion of lipopolysaccharide. At 4 h, ileal myeloperoxidase (MPO) activity and intestinal permeability were measured. The animals in the hypercapnia group showed apparent hypercapnic acidosis and progressive intramucosal acidosis at 4 h, accompanied by significantly lower intestinal permeability versus normocapnia group. Ileal MPO activity was comparable between the study groups. Conclusions  Hypercapnic acidosis attenuates endotoxin-induced gut barrier dysfunction possibly through neutrophil-independent mechanisms. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Validation of the Japanese version of the life satisfaction checklist (LiSat-11) in patients with low back pain: A cross-sectional study

Background

Previous studies suggest that life satisfaction assessment using the Life Satisfaction checklist (LiSat-11) is a meaningful outcome measure and may play an important role in setting rehabilitation goals in patients with chronic pain. Until now, there was no Japanese version of this questionnaire, and the psychometric properties of the original version of the LiSat-11 have only been investigated using classical test theory approaches. The objective of the present study was to evaluate the psychometric properties of the LiSat-11-J using Rasch analysis in a sample of Japanese people with low back pain (LBP).