[Differentiating cochlear synaptopathies into different hearing disorders]. / Differenzierung cochleärer Synaptopathien in verschiedene Hörstörungen.

Due to demographic change and altered recreational behavior, a rapid increase in hearing deficits is expected in the next 20-30 years. Consequently, the risk of age-related loss of speech discrimination, tinnitus, hyperacusis, or-as recently shown-dementia, will also increase. There are increasing indications that the loss of specific hearing fibers in humans and animals is involved in various hearing disorders. This fiber loss can be caused by cochlear synaptopathy or deafferentation and does not necessarily lead to clinically measurable threshold changes. Animal experiments have shown that reduced auditory nerve activity due to acoustic trauma or aging can be centrally compensated by disproportionately elevated and faster auditory brainstem responses (ABR). The analysis of the suprathreshold amplitudes of auditory evoked brain stem potentials and their latency in combination with non-invasive imaging techniques such as magnetic resonance imaging can help to identify the central compensatory ability of subjects and to assign defined hearing deficits.

Unilateral cochlea sparing in locoregionally advanced head and neck cancer: a planning study.

BACKGROUND: Cochlea sparing can reduce late ototoxicity in head and neck cancer patients treated with cisplatin-based radiochemotherapy. In this situation, a mean cochlear dose (MCD) constraint of 10 Gy has been suggested by others based on the dose-effect relationship of clinical data. We aimed to investigate whether this is feasible for primary and postoperative radiochemotherapy in locoregionally advanced tumors without compromising target coverage. PATIENTS AND METHODS: Ten patients treated with definitive and ten patients treated with adjuvant intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy were investigated. The cochleae and a planning risk volume (PRV) with a 3 mm margin were newly delineated, whereas target volumes and other organs at risk were not changed. The initial plan was recalculated with a constraint of 10 Gy (MCD) on the low-risk side. The quality of the resulting plan was evaluated using the difference in the equivalent uniform dose (EUD). RESULTS: A unilateral MCD of below 10 Gy could be achieved in every patient. The mean MCD was 6.8 Gy in the adjuvant cohort and 7.6 Gy in the definitive cohort, while the non-spared side showed a mean MCD of 18.7 and 30.3 Gy, respectively. The mean PRV doses were 7.8 and 8.4 Gy for the spared side and 18.5 and 29.8 Gy for the non-spared side, respectively. The mean EUD values of the initial and recalculated plans were identical. Target volume was not compromised. CONCLUSION: Unilateral cochlea sparing with an MCD of less than 10 Gy is feasible without compromising the target volume or dose coverage in locoregionally advanced head and neck cancer patients treated with IMRT. A prospective evaluation of the clinical benefit of this approach as well as further investigation of the dose-response relationship for future treatment modification appears promising.

Efficacy of MR angiography in the detection and characterization of occlusive disease in the vertebrobasilar system.

PURPOSE: The purpose of this work was to determine the efficacy of MR angiography (MRA) in the detection and characterization of occlusive disease in the vertebrobasilar system. METHOD: We retrospectively reviewed the posterior circulation registry of our institution to select 42 consecutive patients with posterior circulation ischemic symptoms who underwent both MRA and angiography. The extracranial vertebral arteries (ECVAs) were examined by two-dimensional time-of-flight MRA above the C6 level, and the intracranial vertebral arteries (ICVAs) and basilar arteries (BAs) were examined by three-dimensional time-of-flight MRA. Sixty-two ECVAs, 63 ICVAs, and 39 BAs were examined by the readers. RESULTS: Occlusive disease was seen on angiography in 22 of the 42 patients. The sensitivity and specificity values for detection of lesions in 12 ECVA, 19 ICVA, and 12 BA abnormalities were as follows: ECVA, 92 and 96% for Reader A and 100 and 90% for Reader B; ICVA, 84 and 93% for Reader A and 74 and 82% for Reader B; and BA, 100 and 88% for Reader A and 100 and 78% for Reader B. For ICVA, the sensitivity of MRA was less than that of angiography because of lesions missed by the readers at the junctional area of the extra-and intracranial MRA. MRA accurately characterized 9 of the 12 (75%) ECVA, 10 of the 19 (43%) ICVA, and 11 of the 12 (92%) BA lesions. CONCLUSION: MRA is an effective method for detection of occlusive lesions in the ECVAs and BAs. Clinically important lesions can be missed by MRA in the ICVA. MRA is more accurate in characterization of occlusive lesions in BAs than in ECVAs or ICVAs.

Extracellular matrix modulates enterocyte growth via downregulation of c-jun but is independent of p21 and p27 expression.

Regulation of the intestinal crypt-villus axis is multifactorial and involves growth factors and extracellular matrix composition. Laminin, a component of the enterocyte basement membrane, induces enterocyte differentiation and inhibits proliferation. To investigate the mechanism of this observation, we examined the expression of cell cycle modulators in enterocytes cultured on laminin. IEC-6 enterocytes were cultured on collagen I or laminin for 24 hours in media with serum followed by 48 hours of culture in serum-free media. Cells were then stimulated with epidermal growth factor, and RNA and protein were extracted before and up to 18 hours after stimulation. c-jun mRNA expression and p21 and p27 protein expression were analyzed. Expression of c-jun was inhibited in cells grown on laminin as compared to collagen I. Expression of p21 and p27 was no different between cells grown on laminin or collagen I. The mechanism of enterocyte growth inhibition mediated by laminin involves downregulation of c-jun expression. In contrast, p21 and p27 levels were unaffected by extracellular matrix indicating that the changes in expression of these cyclin-dependent kinase inhibitors do not contribute to the effect of laminin on enterocyte proliferation.

Utility of wiring nitrate reductase by alkylpyrroleviologen-based redox polymers for electrochemical biosensor and bioreactor applications.

The purpose of this work was to see if the alkylpyrroleviologen redox polymer technology previously developed for a reagentless nitrate biosensor based on nitrate reductase (NaR) from Escherichia coli (Cosnier, S.; Innocent, C.; Jouanneau, Y. Anal. Chem. 1994, 66, 3198-3201) could be applied to the isozyme from Aspergillus niger. In particular, the enzyme viability after immobilization was of great interest, as Cosnier et al. reported a residual activity of only 0.33% of the amount initially applied. The present work showed that A. niger NaR lost 99.2% of soluble activity on vacuum-drying in the presence of 2.5 nM N-methyl-N'-(12-[pyrrol-1-yl]dodecyl)-4,4'-bipyridinium ditetrafluoroborate monomer (C12V2+) and that most of this loss was due to monomer inhibition (91%). The loss due to dehydration was only 8%. In the biosensor configuration, the enzyme gave a residual activity of 0.18% of the amount originally applied and a specific response of 1.7 mA M-1 cm-2, but all activity was lost after 4 d storage at 4 degrees C in phosphate buffer. It was concluded that for practical biosensors and bioreactors, modification of the redox polymer format was needed, for example by covalent immobilization, to effect higher loading of viable NaR and improved enzyme stability.

Cerebrospinal fluid flow waveforms: effect of altered cranial venous outflow. A phase-contrast MR flow imaging study.

Our purpose was to assess the effect of alterations in the cranial venous outflow on cerebrospinal fluid (CSF) flow waveforms using phase-contrast MRI. Thirteen healthy subjects were assessed for CSF flow and cerebral vascular flow at the C2-3 level, both before and after jugular venous compression (JVC). The flow waveforms were assessed both as an aggregate, and after dividing subjects in two groups based on percent jugular venous flow (PJVF) i.e. jugular outflow expressed as percent of cerebral arterial inflow. Group 1:7 subjects with PJVF more than and including median (predominantly jugular outflow); Group 2:6 subjects with PJVF less than median (predominantly extra-jugular outflow). CSF waveforms: JVC produced rounding of contours and flattening of dicrotic waves, with the effect being greater in group 1 than group 2. In group 1, systolic upslopes of the waveforms increased. No significant aggregate amplitude changes were noted; amplitudes increased in group 1 (P = 0.001), and decreased in group 2 (P = 0.03). Temporal interval to the maximum CSF systolic flow significantly increased in group 1. Vascular flow: Arterial flow significantly decreased in group 1. Jugular flow significantly decreased in both groups. The results suggest that CSF flow waveforms are sensitive to alterations in the cranial venous outflow. Changes in group 1 are most likely because of an elevation in intracranial pressure. Analysis of CSF flow waveforms appears a promising noninvasive tool for assessment of cranial compartment.