Audiological features of GJB2 (connexin 26) deafness

OBJECTIVE: The aim of the present study was to characterize audiological profiles in patients with GJB2 deafness DESIGN: We screened DNA from 399 individuals with nonsyndromic deafness for mutations in the connexin 26 gene (GJB2) by sequence analysis. A total of 77 (19%) of these deaf individuals were biallelic GJB2 mutations (either homozygous or compound heterozygous mutations) (GJB2 deafness). Using the audiological classification criteria of genetic deafness proposed by the European Workshop on Genetic Hearing Loss, we analyzed audiograms of these patients to characterize audiological features of the GJB2 deafness. In addition, we reviewed audiological data of 411 deafness cases from the literature providing details of audiological data (including 157 with GJB2 deafness). RESULTS: All categories of hearing loss severity were found, with significant differences in the findings from GJB2 cases: 1 (4.5%) of 22 individuals with mild hearing loss, 10 (13.3%) of 75 with moderate loss, 14 (14.9%) of 94 with severe loss, and 52 (25%) of 208 with profound deafness (Chi-square test, 3 df, p = 0.016). 81.6% of patients with GJB2 mutations had severe to profound loss, 18.4% with mild to moderate loss (Chi-square test, p = 0.014). The 235delC mutation was always associated with profound deafness. The main audiogram shapes found were residual/sloping (72.7%) and flat (23.4%). There were no differences in the severity and audiogram shapes of the hearing impairment between homozygous and compound heterozygous GJB2 deafness (Chi-square test, p > 0.05). CONCLUSIONS: Our study shows that the probability of finding biallelic GJB2 mutations increases with the severity of hearing loss. Audiograms associated with GJB2 deafness were usually nonspecific. Patients with unknown causes of severe or profound hearing loss should be routinely tested for GJB2 mutations, but due to the variability in hearing loss, individuals with lesser degrees of hearing loss should not be precluded from testing.     

Hyperprolactinemia in some Meniere patients even in the absence of incapacitating vertigo

Stress can be a significant factor influencing ear pathologies and is often reported to trigger the symptoms of Meniere's disease. Both physiological and psychological stress provokes the release of prolactin from the pituitary thus allowing the classification of prolactin as a major stress hormone. We investigated the level of the stress hormone prolactin in a Swedish population with early symptoms of Meniere's disease. The median prolactin level in the Meniere patients (n=33) was not significantly different from that of non-Meniere patients (n=23). However, in the Meniere group one female (90 year old) had prolactin levels in the upper normal range for women, one male (77 year old) had prolactin levels above the normal limit for men, and a third patient (76 year old female) presented hyperprolactinemia with more than twice the normal level. MRI confirmed a pituitary adenoma in this patient. This study provides further support for the recent report of hyperprolactinemia in some patients with long-standing Meniere's disease and presenting incapacitating vertigo in France. The data emphasize the likely implication of stress in this pathology where the stress hormone prolactin is likely to represent one actor in a complex hormonal imbalance affecting the inner ear.     

Validity and reliability of the glottal function index

OBJECTIVE: To evaluate a symptom-focused vocal impairment instrument for the evaluation of patients with voice disorders. DESIGN: Prospective, nonrandomized study of patients with voice disorders undergoing treatment with validation of a new symptom index, the Glottal Function Index (GFI). SETTING: Voice disorders clinic at an academic tertiary care hospital. PATIENTS: Consecutive patients undergoing therapy for glottal insufficiency, adductor spasmodic dysphonia, nodules, and granuloma (40 patients in each group) and 40 control patients. INTERVENTIONS: The Pearson correlation coefficient was used to evaluate GFI reproducibility and to compare it with the Voice Handicap Index (VHI). The paired-samples t test was used to compare pretherapy and posttherapy GFI values. MAIN OUTCOME MEASURES: Correlation of GFI with VHI; comparison of the GFI in normals, and in pretherapy and posttherapy GFI and VHI scores. RESULTS: The mean +/- SD normative GFI score was 0.87 +/- 1.32. The correlation coefficient for GFI between independent pretherapy measurements was 0.56 (P<.001). The correlation coefficient between total GFI and total VHI scores was 0.61 (P<.001). The mean posttherapy GFI scores improved among all groups as follows: glottal insufficiency: presenting GFI score, 12.7 +/- 4.1; posttherapy GFI score, 6.8 +/- 5.4; nodules: presenting GFI score, 12.9 +/- 4.2; posttherapy GFI score, 8.9 +/- 4.6; adductor spasmodic dysphonia: presenting GFI score, 13.2 +/- 4.1; posttherapy GFI score, 8.9 +/- 4.9; and granuloma: presenting GFI score, 7.8 +/- 4.6; posttherapy GFI score, 3.8 +/- 2.1. Relative to controls, the GFI score at presentation was significantly elevated and demonstrated significant reduction following treatment across each of these entities (P<.05). CONCLUSIONS: The GFI is a reliable, reproducible, 4-item, self-administered symptom index with excellent criterion-based and construct validity. Its advantages over existing indexes include brevity and ease of administration. The GFI is a useful adjunct in the evaluation and treatment of patients with glottal dysfunction.     

Language development in preschool-age children adopted from China.

This study examined the language development of 55 preschool-age children adopted from China who had resided in their permanent homes for approximately 2 years or longer. Slightly over 5% of the children scored below average on 2 or more measures from a battery of standardized speech-language tests normed on monolingual English speakers. However, the vast majority scored within or well above the average range on 2 or more measures. Contrary to other reports on the language development of internationally adopted children, the results suggest that "second first language" acquisition proceeds rapidly in the majority of preschool-age children adopted as infants and toddlers. For the children in the sample who scored below average, results indicated that they were among the children who had been exposed to English for the least amount of time. The results of this study demonstrate both the robustness of the language system in the majority of adopted children from China as well as slower growth in a small subset of lower performers in the 1st years after adoption.     

Microglial EP2 as a new target to increase amyloid beta phagocytosis and decrease amyloid beta-induced damage to neurons

Epidemiologic and animal model data support a role for the prostaglandin pathway in AD pathogenesis. However, unexpected toxicity from protracted use of some nonsteroidal anti-inflammatory drugs (NSAIDs) compels investigation of therapeutic targets in this pathway other than COX inhibitors. Previously, we have shown that mice lacking one specific receptor for PGE2, EP2 (EP2-/-), are protected from the indirect neurotoxic effects of cerebral innate immune response mediated by CD14-dependent activation. Here we review data showing that EP2-/- microglia have a highly desirable combination of features: ablated indirect neurotoxicity following exposure to Abeta(1-42) coupled with enhanced phagocytosis of Abeta peptides, both synthetic and those deposited in human brain. These data point to microglial EP2 as a more focused target within the PG pathway for therapy in AD.     

Ovarian transplantation between monozygotic twins discordant for premature ovarian failure

Monozygotic 24-year-old twins presented with discordant ovarian function. One had had premature ovarian failure at the age of 14 years, whereas her sister had normal ovaries and three naturally conceived children. After unsuccessful egg-donation therapy, the sterile twin received a transplant of ovarian cortical tissue from her sister by means of a minilaparotomy. Within three months after transplantation, the recipient's cycles resumed and serum gonadotropin levels fell to the normal range. During the second cycle, she conceived, and her pregnancy progressed uneventfully. At 38 weeks' gestation, she delivered a healthy-appearing female infant.     

The role of histamine in estradiol-induced conditioned consumption reductions

Conditioned consumption reductions (CCRs) develop toward novel taste stimuli as a consequence of associating those tastes with certain physiological changes. Few studies have focused on the neurochemical basis of this learned behavior. The purpose of these experiments was to reexamine the role of histamine in CCRs elicited by estradiol. Previous studies have suggested that histamine mediates CCRs induced by radiation, centrifugal rotation, and estradiol. However, because the animals were trained in a drug state, but tested in a nondrug state, it is possible that state-dependent learning confounded the results of these studies. The following series of experiments was performed to test this possibility for estradiol-induced CCRs. Implementing our own methodologies in Experiment 1, we demonstrated that an estradiol-induced CCR was blocked by treatment with the histamine 1 receptor blocker, chlorpheniramine maleate, before sucrose consumption during acquisition. In Experiment 2, identical states were maintained during acquisition and extinction by administering chlorpheniramine prior to sucrose exposure during both phases. The results indicated that chlorpheniramine blocked the estradiol-induced CCR. However, circumventing state-dependency in Experiment 3 by administering chlorpheniramine following exposure to sucrose during acquisition augmented the estradiol CCR. Taken together, the results of these experiments suggest that the ability of chlorpheniramine to abolish estradiol-induced CCRs is not due to state-dependency or to the antihistaminergic properties of chlorpheniramine. It is proposed that the results of all of the experiments can be accounted for by the aversive properties of chlorpheniramine.