Binaural advantages in using a cochlear implant for adults with profound unilateral hearing loss

Background: Recent studies of cochlear implants (CIs) in profound unilateral hearing loss (UHL) patients have demonstrated a restoration of some binaural hearing.

Aims/Objectives: The objective was to evaluate three possible advantages of binaural hearing in CIs adult users with UHL including single-side deafness (SSD) and asymmetric hearing loss (AHL) subgroups.

Material and methods: A prospective study was conducted that included 70 sequentially implanted patients. Subgroups of these subjects included 64 with a postlingual onset of a profound hearing loss on the implanted side and 6 with a prelingual onset of that loss. Three binaural effects – redundancy, head shadow, and squelch – were evaluated.

Results: Significant differences between the ‘CI on’ and ‘CI off’ conditions were found for all three binaural effects for the study group as a whole and for the postlingual subgroup. However, results for the subjects in the prelingual subgroup did not demonstrate any of the binaural advantages.

Conclusion and significance: Patients with a postlingual onset of a profound hearing loss in one ear and normal hearing or only a moderate loss in the other ear are able to make the effective use of a CI in the profound-loss ear in conjunction with acoustic stimulation of the other ear.     

Growth and functional maturation of beta-cells in implants of endocrine cells purified from prenatal porcine pancreas

The development of islet cell transplantation as a cure for diabetes is limited by the shortage of human donor organs. Moreover, currently used grafts exhibit a marginal beta-cell mass with an apparently low capacity for beta-cell renewal and growth. Although duct-associated nonendocrine cells have often been suggested as a potential source for beta-cell production, recent work in mice has demonstrated the role of beta-cells in postnatal growth of the pancreatic beta-cell mass. The present study investigated whether the beta-cell mass can grow in implants that are virtually devoid of nonendocrine cells. Endocrine islet cells were purified from prenatal porcine pancreases (gestation >110 days) and implanted under the kidney capsule of nude mice. beta-Cells initially presented with signs of immaturity: small size, low insulin content, undetectable C-peptide release, and an inability to correct hyperglycemia. They exhibited a proliferative activity that was highest during posttransplant week 1 (2.6 and 5% bromodeoxyuridine [BrdU]-positive beta-cells 4 and 72 h posttransplant) and then decreased over 20 weeks to rates measured in the pancreas (0.2% BrdU-positive cells). beta-Cell proliferation in implants first compensated for beta-cell loss during posttransplant week 1 and then increased the beta-cell number fourfold between posttransplant weeks 1 and 20. Rates of alpha-cell proliferation were only shortly and moderately increased, which explained the shift in cellular composition of the implant (beta-cell 40 vs. 90% and alpha-cell 40 vs. 7% at the start and posttransplant week 20, respectively). beta-Cells progressively matured during the 20 weeks after transplantation, with a twofold increase in cell volume, a sixfold increase in cellular insulin content, plasma C-peptide levels of 1-2 ng/ml, and an ability to correct diabetes. They became structurally organized as homogenous clusters with their secretory vesicles polarized toward fenestrated capillaries. We concluded that the immature beta-cell phenotype provides grafts with a marked potential for beta-cell growth and differentiation and hence may have a potential role in curing diabetes. Cells with this phenotype can be isolated from prenatal organs; their presence in postnatal organs needs to be investigated.     

Conditional expression of vaccinia virus genes in mammalian cell lines expressing the tetracycline repressor

A new system was developed for producing conditional-lethal vaccinia virus mutants using the tetracycline controlled gene expression system from bacteria. The tetracycline resistance operon (tetO) sequence was placed between the promoter and coding sequence of the target gene of the virus. To regulate the expression of the target gene, the tetO-containing virus was used to infect a tetracycline repressor (TetR) expressing cell line. This method allowed isolation of a tetO-containing virus in the absence of the TetR thereby eliminating the risk of selecting for an inactivated viral tetR gene caused by recombination of the virus genome and improving the stability of the engineered mutants.     

Sociability trait and serotonin metabolism in the rat social interaction test

Social behaviour is the basis of one of the most generally accepted independent dimensions of personality. The purpose of the present study was to find out whether the social activity of individual rats, expressed in the social interaction test of anxiety, is consistent, and associated with monoamine levels. Four social interaction tests with 10 days intervals were carried out in 20 rats, and the animals were decapitated 4 days after the last test. There was no consistent correlation between performances in single tests, but the social interaction time in each test correlated strongly with the mean values of social activity in all or the other three tests. Social interaction time of rats correlated moderately but significantly with their partner's social activity in the test. The average social interaction time correlated strongly with 5-HIAA levels in the frontal cortex (r = -0.67, P < 0.01). Neither exposure of rats singly to the social interaction test box nor the test procedure had any effect on monoamine levels. When animals were decapitated immediately after a single social interaction test, there was a negative correlation between the social interaction time and 5-HIAA and 5-HT levels in the septum, but not in the frontal cortex or hippocampus. Thus, social behaviour is a stable trait, expression of which depends in part upon the partner's social behaviour. This trait is negatively associated with 5-HT metabolism in the frontal cortex. Social activity of rats in a particular test situation may rather be related to 5-HT metabolism in the septum.     

Mondini dysplasia and recurrent bacterial meningitis in a girl with relapsing Langerhans cell histiocytosis

We report a case of a girl with Langerhans cell histiocytosis (LCH) of multifocal bone disease, who developed recurrent bacterial meningitis and unilateral sensorineural hearing loss during the relapsing course of the disease. Mondini dysplasia, a congenital inner ear anomaly, was suspected by high resolution computed tomographic scan and the dysplasia with cerebrospinal fluid leakage was confirmed by surgery in the ipsilateral ear showing hearing loss. Although rare, congenital inner ear anomalies such as Mondini dysplasia should be kept in mind in pediatric patients with hearing impairment and/or recurrent bacterial meningitis during chemotherapy for various types of neoplasms including LCH.     

Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism

BACKGROUND AND OBJECTIVE: Tizanidine, a centrally acting skeletal muscle relaxant, is metabolized mainly by cytochrome P450 (CYP) 1A2 and has a low oral bioavailability. The fluoroquinolone antibiotic ciprofloxacin is only a moderately potent inhibitor of CYP1A2. Our objective was to study the extent and mechanism of a possible interaction of ciprofloxacin with tizanidine. METHODS: In a double-blind, randomized, 2-phase crossover study, 10 healthy volunteers ingested 500 mg ciprofloxacin or placebo twice daily for 3 days. On day 3, a single dose of 4 mg tizanidine was ingested 1 hour after the morning dose of ciprofloxacin. Plasma concentrations of tizanidine and ciprofloxacin and pharmacodynamic variables were measured. A caffeine test was used as a marker for CYP1A2 activity. RESULTS: Ciprofloxacin increased the area under the plasma concentration-time curve from time 0 to infinity [AUC(0-infinity)] of tizanidine by 10-fold (range, 6-fold to 24-fold; P < .001) and its peak concentration by 7-fold (range, 4-fold to 21-fold; P < .001), whereas its elimination half-life was only prolonged from 1.5 to 1.8 hours (P = .007). The pharmacodynamic effects of tizanidine were much stronger during the ciprofloxacin phase than during the placebo phase with regard to changes in systolic blood pressure (-35 mm Hg versus -15 mm Hg, P = .001), diastolic blood pressure (-24 mm Hg versus -11 mm Hg, P < .001), Digit Symbol Substitution Test (P = .02), subjective drug effect (P = .002), and subjective drowsiness (P = .009). The AUC(0-infinity) of tizanidine and its change correlated (P < .01) with the caffeine/paraxanthine ratio and its change. CONCLUSIONS: Ciprofloxacin greatly elevates plasma concentrations of tizanidine and dangerously potentiates its hypotensive and sedative effects, mainly by inhibiting its CYP1A2-mediated metabolism, at least when administered 1 hour before tizanidine. Tizanidine seems to be a useful probe drug for measuring presystemic metabolism by CYP1A2. Care should be exercised when tizanidine is used concomitantly with ciprofloxacin.