Ear-canal acoustic admittance and reflectance measurements in human neonates. II. Predictions of middle-ear in dysfunction and sensorineural hearing loss

This report describes relationships between middle-ear measurements of acoustic admittance and energy reflectance (YR) and measurements of hearing status using visual reinforcement audiometry in a neonatal hearing-screening population. Analyses were performed on 2638 ears in which combined measurements were obtained [Norton et al., Ear Hear. 21, 348-356 (2000)]. The measurements included distortion-product otoacoustic emissions (DPOAE), transient evoked otoacoustic emissions (TEOAE), and auditory brainstem responses (ABR). Models to predict hearing status using DPOAEs, TEOAEs, or ABRs were each improved by the addition of the YR factors as interactions, in which factors were calculated using factor loadings from Keefe et al. [J. Acoust. Soc. Am. 113, 389-406 (2003)]. This result suggests that information on middle-ear status improves the ability to predict hearing status. The YR factors were used to construct a middle-ear dysfunction test on 1027 normal-hearing ears in which DPOAE and TEOAE responses were either both present or both absent, the latter condition being viewed as indicative of middle-ear dysfunction. The middle-ear dysfunction test classified these ears with a nonparametric area (A) under the relative operating characteristic curve of A = 0.86, and classified normal-hearing ears that failed two-stage hearing-screening tests with areas A = 0.84 for DPOAE/ABR, and A = 0.81 for TEOAE/ABR tests. The middle-ear dysfunction test adequately generalized to a new sample population (A = 0.82).     

Analyses of cutaneous fluoroquinolones photoreactivity using the integrated model for the differentiation of skin reactions

Currently available test models for the differentiation of photoallergic and photoirritant reactions are extremely time consuming and the protocols are very heterogeneous. In vitro tests are of proven value in predicting irritant or toxic effects, but these tests fail to predict chemical-induced allergic side effects. We developed test systems for this endpoint which is not easily detected by existing assays. In a previous publication we were able to discriminate between a contact sensitizer and a skin irritant with a combination of primary ear swelling analysis and cell counting of the ear-draining lymph nodes [Toxicol. Appl. Pharm. 153 (1998) 83; Arch. Toxicol. 73 (2000) 501]. This combination of tests was called the Integrated Model for the Differentiation of chemical-induced allergic and irritant Skin reactions (IMDS). In addition, it had been shown before that inclusion of UV irradiation in the local lymph node assay enables discrimination of photoallergic from photoirritant reactions after dermal application [Photodermatol. Photoimmunol. Photomed. 10 (1994) 57]. Because of the fact that fluoroquinolones are known to induce photoreactions after oral but not dermal treatment, the aim of the present study was to apply the IMDS for the fast and reliable differentiation of photoreactions due to fluoroquinolones after oral treatment. Enoxacin, lomefloxacin, ofloxacin, sparfloxacin and BAY y 3118 were tested in this system. We found a good correlation between the results of UV light-irradiated IMDS and a guinea pig model with the quinolones as far as photoirritancy was concerned. This holds true also for the photoallergic standard olaquindox and the photoirritant standard 8-methoxypsoralen. However, in contrast to the guinea pig assays the IMDS is fast and extremely predictive for the risk of both photosensitization and photoirritancy depending on the route of exposure. Thus, the UV light-irradiated IMDS turned out to be a good tool for the preclinical risk assessment procedure in terms of discriminating photoreactions. In addition, flow cytometric analyses were used to underline the fact that antigen-independent activation occurred after the induction of photoirritant reactions.     

Summation methods of Coulomb interactions in computer simulations of a system with one—dimensional periodic boundary conditions

The Ewald-type method, its modified version and the Lekner-type method for summing Coulomb interactions in a system periodic along one direction are presented and compared. Advantages and disadvantages of these methods are discussed, and the methods are tested in molecular dynamics simulations of acetone molecules confined to cylindrical silica pores.     

Electrostatic interactions in molecular dynamics simulation of a three-dimensional system with periodicity in one direction

The Mellin transform and Poisson summation formula are used to derive an expression for the Coulomb interaction energy of a three-dimensional system with periodicity in one direction. Initially, calculations are performed for interactions characterized by any inverse power and, using the analytical continuation of the energy function, one obtains the final expression for the interaction energy of charges. We consider also a special case when two different charges are located on a line parallel to the periodicity direction. The energy and force expressions are identical to those obtained from the Lekner summation which is simply a sum over reciprocal lattice terms. The convergence behaviour of the Lekner summation is compared with that based on the Ewald type approach.     

Coulomb interactions in a computer simulation of a system periodic in two directions

The integral representation of the gamma function and the Poisson summation formula are used to calculate the interaction energy of charged particles in a 3-dimensional system periodic in two directions. A parallelogram shape simulation box is considered. Calculations are carried out for interactions described by any inverse power, and analytical continuation of the energy function leads to the final expression for the Coulomb interaction energy. Summation over the simulation box replica along one or the other side of the box base is replaced by summation in reciprocal space. Therefore there are two equivalent formulas for the potential energy that offer the possibility of avoiding slowly convergent series. The energy expressions are identical to those obtained from the Lekner method. The special case is considered where the functions defining the energy are infinite, i.e. when two charges lie on a line parallel to the simulation box side that was chosen to convert real space summation into reciprocal space.     

Evaluation of phototoxic and photoallergic potentials of 13 compounds by different in vitro and in vivo methods

Phototoxic side effects of pharmaceutical and cosmetic products are of increasing concern for patients, dermatologists and the chemical industry. Moreover, the need of new chemicals and drugs puts pressure on pre-clinical test methods for side effects, especially interactive adverse-effects with UV-light. So, the predictive potential of different established test methods, which are used regularly in our departments in order to detect the phototoxic potential of chemicals, were analyzed. Namely the fibroblast 3T3 test, the photo hen's egg test, a guinea pig test for measuring acute photoreactions, and a modified Local Lymph Node Assay, the Integrated Model for the Differentiation of Skin Reactions. Various agents with different photoreactive potential were tested: quinolones like Bay y 3118, ciprofloxacin, enoxacin, lomefloxacin, moxifloxacin, ofloxacin, sparfloxacin, as well as promethazine, chlorpromazine, 8-methoxypsoralen and olaquindox serving as control. Special emphasis was taken to evaluate the capability of the employed test procedures to predict phototoxic side effects in patients. Following our results, both in vitro assays were useful tools to detect photoirritancy while the photoallergic potentials of tested compounds were exclusively detected by an in vivo assay. As long as no in vitro model for photoallergy is available, the UV-IMDS should be considered to evaluate photoallergic properties of a supposed photoreactive agent.     

Ear-canal acoustic admittance and reflectance effects in human neonates. I. Predictions of otoacoustic emission and auditory brainstem responses

This report describes the extent to which ear-canal acoustic admittance and energy reflectance (YR) in human neonates (1) predict otoacoustic emission (OAE) levels and auditory brainstem response (ABR) latencies, and (2) classify OAE and ABR responses as present or absent. Analyses are reported on a subset of ears in which hearing screening measurements were obtained previously [Norton et al., Ear. Hear. 21, 348-356 (2000a)]. Tests on 1405 ears included YR, distortion-product OAEs, transient-evoked OAEs, and ABR. Principal components analysis reduced the 33 YR variables to 5-7 factors. OAE levels decreased and ABR latencies increased with increasing high-frequency energy reflectance. Up to 28% of the variance in OAE levels and 12% of the variance in ABR wave-V latencies were explained by these factors. Thus, the YR response indirectly encodes information on inter-ear variations in forward and reverse middle-ear transmission. The YR factors classify OAEs with an area under the relative operating characteristic (ROC) curve as high as 0.79, suggesting that middle-ear dysfunction is partly responsible for the inability to record OAEs in some ears. The YR factors classified ABR responses less well, with ROC areas of 0.64 for predicting wave-V latency and 0.56 for predicting Fsp.