Eosinophilic otitis media and eosinophilic asthma: Shared pathophysiology and response to anti-IL5

Asthma is a highly prevalent airway disease with multiple phenotypes [1,2]. Adult-onset eosinophilic asthma is a severe asthma subtype associated with more frequent and severe exacerbations, the development of persistent airflow limitation and a poorer quality of life. This type of asthma is much more difficult to control than other asthma subtypes, requiring high doses of inhaled or even oral corticosteroids (OCS) [3,4]. Recently, several new monoclonal antibody therapies have been approved for eosinophilic severe asthma, including anti-IL-5 treatment. IL-5 is essential for eosinophilic maturation and survival [5] and anti-IL5 treatment has markedly reduced asthma exacerbations with sparing of OCS use in patients with eosinophilic asthma [6]. Eosinophilic asthma is frequently associated with chronic rhinosinusitis and/or nasal polyposis [7], suggesting that a similar eosinophilic inflammatory process might drive both conditions. Eosinophilic otitis media (EOM) also might fit in this concept, showing remarkable similarities with asthma and nasal polyposis. The disease was first reported in 1994, but only since 2011 diagnostic criteria for EOM were identified. If a patient shows otitis media with effusion or chronic otitis media with eosinophil-dominant effusion (major criterion) and is being positive for ≥2 items of the 4 minor criteria (highly viscous middle ear effusion, resistance to conventional treatment, association with asthma, association with nasal polyposis) he is diagnosed as having EOM. Eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome must be excluded [8]

Long-term effects of carotid sinus Denervation on arterial blood pressure in humans

Background-After experimental carotid sinus denervation in animals, blood pressure (BP) level and variability increase markedly but normalize to preoperative levels within 10 to 14 days. We investigated the course of arterial BP level and variability after bilateral denervation of the carotid sinus baroreceptors in humans. Methods and Results-We studied 4 women (age 41 to 63 years) who were referred for evaluation of arterial baroreflex function because of clinical suspicion of carotid sinus denervation attributable to bilateral carotid body tumor resection. The course of BP level and variability was assessed from repeated office and 24-hour ambulatory measurements (Spacelabs/Portapres) during I to 10 years of (retrospective) follow-up. Rapid cardiovascular reflex adjustments to active standing and Valsalva's maneuver were assessed. Office BP level increased from 132/86 mm Hg (range, 118 to 148/80 to 92 mm Hg) before bilateral surgery to 160/105 mm Hg (range, 143 to 194/90 to 116 mm Hg) 1 to 10 years after surgery. During continuous 24-hour noninvasive BP recording (Portapres), a marked BP variability was apparent in all 4 patients. Initial symptomatic hypotension on change to the upright posture and abnormal responses to Valsalva's maneuver were observed. Conclusions-Acute carotid sinus denervation, as a result of bilateral carotid body tumor resection, has a long-term effect on the level. variability, and rapid reflex control of arterial BP. Therefore, in contrast to earlier experimental observations, the compensatory ability of the baroreceptor areas outside the carotid sinus seems to be of limited importance in the regulation of BP in human

Genetic Heterogeneity of Usher Syndrome: Analysis of 151 Families with Usher Type I

Usher syndrome type I is an autosomal recessive disorder marked by hearing loss, vestibular areflexia, and retinitis pigmentosa. Six Usher I genetic subtypes at loci USH1A–USH1F have been reported. The MYO7A gene is responsible for USH1B, the most common subtype. In our analysis, 151 families with Usher I were screened by linkage and mutation analysis. MYO7A mutations were identified in 64 families with Usher I. Of the remaining 87 families, who were negative for MYO7A mutations, 54 were informative for linkage analysis and were screened with the remaining USH1 loci markers. Results of linkage and heterogeneity analyses showed no evidence of Usher types Ia or Ie. However, one maximum LOD score was observed lying within the USH1D region. Two lesser peak LOD scores were observed outside and between the putative regions for USH1D and USH1F, on chromosome 10. A HOMOG χ(2)((1)) plot shows evidence of heterogeneity across the USH1D, USH1F, and intervening regions. These results provide conclusive evidence that the second-most-common subtype of Usher I is due to genes on chromosome 10, and they confirm the existence of one Usher I gene in the previously defined USH1D region, as well as providing evidence for a second, and possibly a third, gene in the 10p/q region