Biomedical subjects
Publications and source records attributed to K Stephan.
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Titan is the only satellite in our Solar System with a dense atmosphere. The surface pressure is 1.5 bar (ref. 1) and, similar to the Earth, N2 is the main component of the atmosphere. Methane is the second most important component, but it is photodissociated on a timescale of 10(7) years (ref. 3). This short timescale has led to the suggestion that Titan may possess a surface or subsurface reservoir of hydrocarbons to replenish the atmosphere. Here we report near-infrared images of Titan obtained on 26 October 2004 by the Cassini spacecraft. The images show that a widespread methane ocean does not exist; subtle albedo variations instead suggest topographical variations, as would be expected for a more solid (perhaps icy) surface. We also find a circular structure approximately 30 km in diameter that does not resemble any features seen on other icy satellites. We propose that the structure is a dome formed by upwelling icy plumes that release methane into Titan's atmosphere.
Voltage-gated Ca(2+) channels formed by subunits (class D Ca(2+) channels) tightly regulate neurotransmitter release from cochlear inner hair cells (IHCs) by controlling the majority of depolarisation-induced Ca(2+) entry. We have recently shown that the absence of these channels can cause deafness and degeneration of outer hair cells (OHCs) and IHCs in alpha1D-deficient mice (alpha1D(-/-)) (Platzer et al., 2000. Cell 102, 89-97). We investigated the time-dependent patterns of degeneration during postnatal development in the alpha1D(-/-) mouse cochlea using light and electron microscopy. At postnatal day 3 (P3), electron microscopy revealed no morphological aberrations in sensory cells, in afferent as well as in efferent nerve endings. But at P7 we observed a beginning degeneration of afferent nerve fibres by electron microscopy. By P15, we found a loss of OHCs in apical turns but electron microscopy revealed no ultrastructural changes in IHCs and efferent axons as compared to C57 black control animals (C57BL). We demonstrated by serial ultrathin sectioning of 15 days old alpha1D(-/-) mice that intact efferent nerve fibres formed direct contacts with IHCs as the degeneration of afferent nerve fibres progressed. We also saw a notable degeneration of spiral ganglion cells at P15. By 8 months, nearly all spiral ganglion and sensory cells of the organ of Corti were absent. Random ultrathin sectioning gave the impression that synaptic bodies abundant in wild-type animals were absent in nearly all alpha1D(-/-) mice investigated. We conclude that besides presumably reduced synaptic bodies the absence of class D L-type Ca(2+) channels does not prevent morphological development of the cochlea until P3 but may cause cochlear degeneration thereafter. The observed pattern of degeneration involves afferent nerve fibres (P7) followed by cell bodies in the spiral ganglion (P15), OHCs (P15) and IHCs (after P15).
OBJECTIVE: To investigate the tolerability of N-chlorotaurine, a new antimicrobial agent, by application to the middle ear in a mouse model. METHODS: Five BALB/c mice were each injected through the tympanic membrane with 5 microL of 0.1%, 1.0%, and 10% N-chlorotaurine and compared with animals in which 0.9% isotonic sodium chloride solution, 0.2% gentamicin sulfate, and 0.25% trimethyltin chloride were instilled. Auditory brainstem responses to clicks were evaluated repeatedly between 4 and 75 days after injection, and histologic investigations of the inner ear were performed subsequently. Three additional groups of mice were injected with isotonic sodium chloride solution, 1.0% N-chlorotaurine, and 0.25% trimethyltin, and brainstem responses to tone bursts of 8, 16, and 32 kHz were tested. In addition, the middle ear was examined histologically. RESULTS: Mice treated with isotonic sodium chloride solution, 0.1% N-chlorotaurine, and 0.2% gentamicin sulfate did not show changes in response threshold. Treatment with 1.0% and 10% N-chlorotaurine caused a reversible increase in auditory brainstem response threshold by 20 dB 4 days after application because of local irritation around the perforation of the tympanic membrane. In contrast, 0.25% trimethyltin showed a permanent elevation of auditory brainstem response threshold of 10 to 15 dB and a scattered loss of outer hair cells predominantly in the apical turn. No alterations of the inner ear were observed in the other treatment groups. The mucous membrane of the middle ear remained unaffected in all test groups. CONCLUSION: Application of N-chlorotaurine to the middle ear is well tolerated without adverse effects and may be a useful new endogenous antimicrobial agent for local treatment of otologic infections.
In order to improve early detection of congenital permanent childhood hearing impairment the Austrian ENT society recommended in 1995 that universal neonatal hearing screening be introduced ("Millstätter Concept"). Coverage is presently about 67% for full-term healthy neonates and 86% for neonates from intensive care units. For maternity units, referral rates between 1% and 3.7% have been reported (2.7-15% for intensive care units). The results of the screening test and follow-up in cases of failure have been documented in 37,543 neonates. Of this population, 91 infants (2.4 per 1000) showed bilateral permanent hearing loss. In these children intervention and management of the family started within the first months of life. These results justify the effort involved in introducing universal neonatal hearing screening.
Voltage-gated L-type Ca2+ channels (LTCCs) containing a pore-forming alpha1D subunit (D-LTCCs) are expressed in neurons and neuroendocrine cells. Their relative contribution to total L-type Ca2+ currents and their physiological role and significance as a drug target remain unknown. Therefore, we generated D-LTCC deficient mice (alpha1D-/-) that were viable with no major disturbances of glucose metabolism. alpha1D-/-mice were deaf due to the complete absence of L-type currents in cochlear inner hair cells and degeneration of outer and inner hair cells. In wild-type controls, D-LTCC-mediated currents showed low activation thresholds and slow inactivation kinetics. Electrocardiogram recordings revealed sinoatrial node dysfunction (bradycardia and arrhythmia) in alpha1D-/- mice. We conclude that alpha1D can form LTCCs with negative activation thresholds essential for normal auditory function and control of cardiac pacemaker activity.
OBJECTIVE: While transmission of drug-resistant HIV-1 has been reported, estimates of prevalence of resistance in drug-naïve populations are incomplete. We investigated the prevalence of genotypic mutations and phenotypic antiretroviral resistance in a cohort of HIV-1 infected U.S. military personnel prior to the institution of antiretroviral therapy. DESIGN: Cross-sectional cohort study. METHODS: Plasma was obtained from 114 recently HIV-1 infected subjects enrolled in an epidemiological study. Genotypic resistance was determined by consensus sequencing of a PCR product from the HIV-1 pol gene. Sequences were interpreted by a phenotypic-genotypic correlative database. Resistance phenotypes were determined by a recombinant virus cell culture assay. RESULTS: Genotypic mutations and phenotypic resistance were found at a higher than expected frequency. Resistance to non-nucleoside reverse transcriptase inhibitors was most common, with a prevalence of 15% of 95 subjects by genotype and 26% of 91 subjects by phenotype. Genotypic and phenotypic resistance respectively were found in 4% and 8% of subjects for nucleoside reverse transcriptase inhibitors and in 10% and 1% for protease inhibitors. One subject harbored virus with resistance to all three drug classes. CONCLUSIONS: A substantial frequency of resistance to antiretroviral drugs was identified in a therapy-naïve U.S. cohort. In most cases, the genotypic and phenotypic assays yielded similar results, although the genotypic assay could detect some protease inhibitor resistance-associated mutations in the absence of phenotypic resistance. These data suggest the need for optimization of treatment guidelines based on current estimates of the prevalence of drug resistance in HIV-1 seroconverters.
To assess the potential for aerosol administration of vaccines for Venezuelan equine encephalitis virus (VEE), we compared the neurovirulence and tissue tropism of the wild-type Trinidad donkey (TrD) strain to those of the attenuated TC83 and V3526 strains of VEE in mice. Six to 8-week-old female C3H/HeN and BALB/c mice were aerosol exposed to one of the three VEE strains. Three mice of each strain were euthanatized at different times and their tissues were processed and stained using hematoxylin and eosin, immunohistochemistry, and in situ hybridization. All three viral strains infected the brains of mice and induced encephalitis. TrD spread caudally from the olfactory bulbs to all regions of the brain, caused widespread necrotizing panencephalitis by day 5, and resulted in 100% mortality (geometric mean = 7 days) in both mouse strains. By comparison, TC83 relatively spared the caudal regions of the brain but still caused 100% mortality in the C3H/HeN mice (geometric mean = 12 days), yet it did not kill any BALB/c mice. V3526 infectivity of the brain was the most limited, mainly affecting the neocortex and diencephalon. This virus was not lethal in either mouse strain. The TrD strain also infected the olfactory neuroepithelium, local lymphoid tissues, teeth, and vomeronasal organs, whereas the affinity of TC83 and V3526 outside the brain was essentially limited to the olfactory neuroepithelium. Attenuated VEE strains administered to mice by aerosol have restricted tissue tropism as compared with wild-type virus; however, even attenuated strains can infect the brain and induce encephalitis.
> Objective: For more than 20 years, vibroacoustic stimulation testing (VAST) using an artificial larynx has been used worldwide when fetal heart rate monitoring produced patterns with absent or very low variability. In addition to the artificial larynx many other appliances have been used to stimulate a seemingly dormant fetus, but these have rarely been evaluated properly. In this study we tried to evaluate the use of standard mechanical wind-up alarm clocks for VAST. Methods: VAST with an alarm clock was performed successfully in 80 women with normal pregnancies from 36 weeks to term. It was tested by placing the alarm clock on the maternal abdomen just above the fetal head or on the controlateral side of the maternal abdomen to see whether position made any difference and whether coupling with ultrasound gel applied between the alarm clock and the maternal abdomen would affect the degree of fetal reaction to VAST as expressed in heart rate acceleration. Similarly, the effect of the alarm clock VAST on subjective and objective fetal movement patterns as registered by kineto-cardiotocotraphy (K-CTG) in addition to heart rate patterns was investigated. Results: All fetuses showed heart rate acceleration, an increase in heart variability, and increase in movement patterns in the 6 min after the application of alarm clock VAST. No statistically significant difference was found which would favor a particular placement of the alarm clock on the maternal abdomen or the use of ultrasound coupling gel. When K-CTG was performed, patient-perceived fetal movements as expressed with an event marker showed agreement with the machine-registered movements only when patients could see the tracing during registration and no accordance when the K-CTG was turned toward the wall during registation. Conclusion: In keeping with the ALARA principle a conventional wind-up alarm clock appears to be an inexpensive and effective alternative to the electrolarynx.
One of the major drawbacks using transient evoked otoacoustic emissions (TEOAEs) for hearing screening in newborn infants is the high fail rate in normal-hearing children. The purpose of the present study was to improve the overall performance of the test procedure and reduce of the fail rate. Improvement was obtained by 3 modifications: (1) change of the pass criterion in healthy newborns by requiring TEOAEs in at least one ear and nor both ears, (2) performing the test only after the second post-partum day, and (3) using a second-stage screening prior to hospital discharge in newborns who failed the initial test. In all, 3980 newborns from 2 well-baby clinics and 243 newborns from a neonatal intensive care unit (NICU) were screened using an system ILO-88 system program mode quick-check test was completed in 3820 infants. Considering these modifications, the pass rate of healthy newborns was improved from 79.5% to > 99%, and only 0.7% of the false negative (healthy) newborns required further audiological evaluation. Babies from the NICU failed in 3.8% of the screening tests. Overall, the number of newborns who failed the ILO-88 screening test was significantly reduced and the fail rate minimize when compared to previously published experiences with TEOAEs in new-born hearing screening.
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From 23 weeks of gestation some and from 28 weeks all healthy fetuses are capable of reacting to sound stimulation. The intrauterine acoustic environment is dominated by maternal sounds--heartbeat, breathing, the mother's voice, borborygmi and sounds caused by body movements. Background noise is never below 28 dB and can rise to 84 dB when the mother is singing. Noises that are meant to reach the fetus must be louder than the background noise and must be of low frequency as high frequency sounds are damped by maternal tissue. Vibroacoustic stimulation tests (VAST) have become popular in pregnancy surveillance over the last 20 years, mostly using an artificial larynx. Advantages and problems of the various VAST protocols in fetal monitoring are discussed in the light of animal experiments and clinical studies. Health legislation laws in most countries forbid pregnant women to work in surroundings with a high noise level (80 dB continuous noise and/or rapid impulse noise changes of 40 dB). Whereas regulations for pregnant women are easy to enforce in industry, pregnant women employed in discos or performing as musicians spend most of their working day exposed to noise impact higher than the recommended limit.
OBJECTIVE: In children supplied with cochlear implants (CIs), there is an urgent need for objective tests for the assessment of electrostimulation. SETTING: An optimized procedure for intraoperative and post-operative applications with short duration test time, based on the measurement of the electrical farfield picked up from surface electrodes on the scalp, is presented; therefore, assessment of stimulation is independent of the stimulating electronic circuitry. OUTCOME: The setup was designed for the COMBI40 multichannel CI using a synchronized sampling technique of the amplified signals. The evaluation procedure includes examination of the time course of the signal and calculation of the input output function. With these options, a straightforward judgment of the electrical performance of the implant in situ, reflecting the input to the auditory nerve, is provided.
The efficacy of the ginkgo biloba special extract EGb 761 in outpatients with presenile and senile primary degenerative dementia of the Alzheimer type (DAT) and multi-infarct dementia (MID) according to DSM-III-R was investigated in a prospective, randomized, double-blind, placebo-controlled, multi-center study. After a 4-week run-in period, 216 patients were included in the randomized 24-week treatment period. These received either a daily oral dose of 240 mg EGb 761 or placebo. In accordance with the recommended multi-dimensional evaluation approach, three primary variables were chosen: the Clinical Global Impressions (CGI Item 2) for psychopathological assessment, the Syndrom-Kurztest (SKT) for the assessment of the patient's attention and memory, and the Nürnberger Alters-Beobachtungsskala (NAB) for behavioral assessment of activities of daily life. Clinical efficacy was assessed by means of a responder analysis, with therapy response being defined as response in at least two of the three primary variables. The data from the 156 patients who completed the study in accordance with the study protocol were taken into account in the confirmatory analysis of valid cases. The frequency of therapy responders in the two treatment groups differed significantly in favor of EGb 761, with p < 0.005 in Fisher's Exact Test. The intent-to-treat analysis of 205 patients led to similar efficacy results. Thus, the clinical efficacy of the ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type and multi-infarct dementia was confirmed. The investigational drug was found to be well tolerated.
BACKGROUND: Cavernous hemangiomas of the optic nerve head are rare, but their clinical features are typical. Further examinations, like fluorescein angiography and echography are necessary for a diagnostic work up. METHODS: In June 1994 we observed a case of a cavernous hemangioma of the optic nerve head. Ophthalmological, fluoresceinangiographical and echographical examinations were done. RESULTS: A 17-year-old woman is presented. The tumor was unilateral, only involving the optic nerve head. During a follow up period of 18 months the tumor remained unchanged. CONCLUSION: In this patient, as in others before, ophthalmoscopical findings are characteristic for a cavernous hemangioma. Fluorescein angiography and especially the standardized echography establish the diagnosis and are helpful for accurate follow up examinations. Usually treatment of cavernous hemangiomas is unnecessary, they remain stable and usually do not cause complications. When vitreous hemorrhage occurs, vitrectomy may be indicated.
Based on a variety of experimental and clinical studies the diagnostic significance of transient evoked otoacoustic emissions (TEOAEs) is well established. This is also due to the availability of commercial hardware and software which is optimized for the recording of click-evoked OAEs. In cases with distortion product otoacoustic emissions (DPOAEs) the significance for clinical purposes is not yet clear. This study presents results obtained in normal hearing subjects and patients with sensorineural hearing losses (214 ears). The study focuses on three problems: 1. Incidence of DPOAEs in different groups of hearing loss. 2. Level of DPOAEs at various frequencies in each group of hearing loss. 3. Frequency-specific relationships between hearing loss and DPOAEs. Recording of DPOAEs was performed with the ILO92 system and standard configuration (primary tone level, 70 dB SPL). In normal hearing ears DPOAEs were observed at all frequencies above 1 kHz. In cases with moderate hearing loss the detection rate decreased to about 80%. With further increases in hearing loss the detection rate and level of DPOAEs decreased. At frequencies below 1500 Hz even in normal hearing subjects, the level of DPOAEs only slightly exceeded the noise level. The upper limit of hearing loss for which DPOAEs could be observed depended on frequency. In the low-frequency range DPOAEs were absent in ears with a sensorineural hearing loss greater than 35-45 dB; at frequencies between 4 and 6 kHz DPOAEs were observed even in ears with a hearing loss 65 dB.(ABSTRACT TRUNCATED AT 250 WORDS)
The response time of the instrument is a crucial parameter for the measurement of accurate morphology and latency of the acoustic reflex. An improved impedance meter accounting for this particular problem was designed for the measurement of the contralateral acoustic reflex. The temporal characteristic of the measurement apparatus will be shown, as well as an example of an application in a normal hearing individual. The module can be incorporated into already existing instruments with some modifications.
In a 6-year-old boy with idiopathic unilateral deafness, click-evoked otoacoustic emissions were recorded in both ears with similar amplitudes and time courses. Following stimulation of the deaf ear, no component of auditory-evoked brainstem potentials was recorded. No space-occupying lesion was observed with high-resolution CT. At retest 1 year later these results were unchanged. In the deaf ear electrostimulation of the cochlear nerve was performed using an ear canal electrode. At a stimulus current of 20 microA the body consistently reported hearing sensation. Click-evoked otoacoustic emission indicated good outer hair cell function. Hearing sensation at low stimulus intensities with electrostimulation indicated fairly good functions of the cochlear nerve. Considering also the results of imaging and auditory-evoked potentials, findings suggested that the deafness was due to an inner hair cell disorder.