Interaction between beta2 adrenergic receptor polymorphisms determines the extent of isoproterenol-induced vasodilatation ex vivo.

OBJECTIVES: Single nucleotide polymorphisms at nucleotides 46, 79 and 491 of the beta2 adrenergic receptor (beta2AR) gene modify its pharmacological properties and may alter the response to agonists. The purpose of this study was to evaluate the role played by beta2AR polymorphisms on isoproterenol-induced relaxation of internal mammary arteries ex vivo. METHODS: Internal mammary leftover segments were collected from 96 patients undergoing coronary artery bypass operation. Vascular rings were allowed to reach equilibrium with physiological Krebs solution before precontraction with U46619. Using the organ bath technique, cumulative dose-response curve of isoproterenol was constructed and average EC50 calculated. beta2AR genotyping was performed using a PCR-RFLP analysis. RESULTS: Arterial segments obtained from Gly16 homozygotes displayed reduced sensitivity to isoproterenol compared with carriers of Arg16 allele(s) [Mean (-log) EC50+/-SD, 6.42+/-0.24, 95% confidence interval (CI) 6.32-6.53 vs. 6.67+/-0.25, 95% CI 6.62-6.73, P<0.001]. Among Gly16 homozygotes, the presence of two Glu27 alleles restored vascular response to the level noted among Arg16 carriers (6.58+/-0.17, 95% CI 6.41-6.76). The least response to isoproterenol was noted in a single patient carrying the Gly16Gly-Gln27Glu-Thr164Ile combined genotype requiring almost six-fold higher isoproterenol concentration than carriers of the wild-type genotype to achieve half the maximal arterial dilatation (17.78 x 10(-7) vs. 3.01 x 10(-7) +/- 2.62 x 10(-7) mol/l). CONCLUSIONS: Vascular dilatation by isoproterenol is determined by a complex interaction between polymorphisms at nucleotides 46, 79 and 491 of the beta2AR gene. Further studies are warranted to evaluate the effect of additional polymorphisms in the coding and noncoding regions on vascular reactivity.

[Cochlear implantation in children with otitis media: third stage of a long-term prospective study].

INTRODUCTION: The age at which cochlear implantation (CI) is performed in children generally corresponds to the age at which the prevalence of otitis media (OM) is highest. The risks of problematic middle ear infection and of potential spread of middle ear infection along the electrode array into the cochlea and the central nervous system are relatively high. Thus, it is necessary to establish a practicable protocol aimed at controlling OM prior to and after CI in young candidates. OBJECTIVE: To assess the risk for otitis media after cochlear implantation in otitis media (OM)-prone and non-OM-prone children who were treated according to a structured protocol designed to control OM prior to implantation. PATIENTS AND METHODS: Of 113 children referred for cochlear implantation during the study period, and were implanted under the age of 7 years, 70 were classified as OM-prone (Group A) and 43 as non-OM-prone (group B). Group A patients were managed according to a structured protocol aimed at pre-implantation control of OM. Postimplantation follow-up ranged from 6 to 75 months (average 35.5 months). RESULTS: In the OM-prone group of children, the mean age at referral and at implantation was significantly lower and the mean interval between referral and implantation significantly higher than in the healthy group. During the first month after implantation 18 children suffered from acute otitis media, the vast majority of them (16) belonged to the OM-prone children (22.8% of this group) and 2 subjects belonged to the non-OM-prone children (4.6% of this group). During the late post-operative period 28 of the OM-prone children (40%) and 4 of the non-OM-prone children (9.3%) developed acute OM in the implanted ear. Eleven (9.7 %) of these cases, (10 belonging to the OM-prone group B (14%), and one belonging to the non-OM-prone group A (2.3%)) proved to be recurrent and therapeutically challenging. Three subjects developed acute mastoiditis without intracranial complications. Each episode of mastoiditis or otitis media was controlled conservatively without any need of surgical drainage of the mastoid. This group of challenging cases did not differ from the OM-prone children who did not prove to be OM-challenging post-CI in regards to age at referral, age at CI and average number of ventilation tube (VT) operations prior to CI. Most pathogen isolations (65%) from OM or from VT drainage developed after CI were typical pathogens for acute otitis media (AOM). However, the percentage of non-typical AOM pathogen isolation increased with time after CI. CONCLUSIONS: Early referral led to early implantation, even in children susceptible to OM. The incidence of OM decreased after implantation in both groups, but was still significantly higher in the OM-prone group. Meanwhile, prior to CI it is not possible to predict the cases that become therapeutically challenging at a later stage.