Quantitative evidence for cochlear, non-neuronal norepinephrine

Endogenous norepinephrine was quantitatively measured in cochlear tissues of pigmented and non-pigmented animals by high-performance liquid chromatography and electrochemical detection. Epinephrine, dopamine and serotonin were not detected. The cochlear norepinephrine content of the pigmented animals was found to be more than double that present in corresponding albinos. Cochlear norepinephrine was only minimally depleted 48 h after surgical removal of the superior cervical ganglion. 12 h after administration of reserpine (5 mg/kg), cochlear norepinephrine was partially depleted. These results indicate that the norepinephrine located in the cochlea is probably not confined entirely to noradrenergic nerve terminals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24265/1/0000530.pd

Ototoxicity of toluene in rats

Toluene is a major industrial solvent and substance of abuse which is ototoxic in rats as shown by both behavioral testing and measurement of brainstem auditory evoked response (BAER) thresholds. The objective of this investigation was to examine the morphological (hair cell loss) and functional (BAER threshold elevations) changes resulting from toluene administration. In the preliminary experiment, 5 male Sprague-Dawley rats were dosed by gavage to 0.5 ml toluene/kg body weight/day in corn oil for 21 days then consecutively to 1.0 ml toluene/kg/day for 21 days. In the main experiment, eight male Sprague-Dawley rats were dosed by gavage for eight weeks with 1.0 ml toluene/kg body weight/day in corn oil. Five and six control rats, respectively, received corn oil only. BAER thresholds were recorded from four toluene-treated and four control rats prior to dosing (main experiment) and from all rats after dosing (both experiments). Loss of outer hair cells occurred in all toluene-treated rats in the middle and basal turns of the organ of Corti, with the greatest loss in the third row and progressively less in the second and first rows. This loss was more severe in toluene-treated rats that demonstrated elevated BAER thresholds in midfrequency regions, typically 2-8 kHz. These experiments demonstrate that auditory changes are associated with cochlear hair cell loss in toluene-treated rats. These ototoxic effects of toluene contrast with those of other known ototoxicants, e.g., aminoglycoside antibiotics, in terms of the position of hair cell lesion in the organ of Corti and in the pattern of hair cell loss.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27088/1/0000079.pd

Primary culture of capillary endothelial cells from the spiral ligament and stria vascularis of bovine inner ear

Methods for isolation and culture of microvascular endothelial cells of the inner ear were devised to provide an in-vitro system for studying endothelial functions in this tissue. Capillaries from the stria vascularis and spiral ligament were treated enzymatically to free them from surrounding tissue. Contamination by extraneous tissue was minimized by banding capillary segments in Percoll gradients and culture in plasma-derived serum on a fibronectin-coated substrate. Although only small amounts of inner ear tissue were available, tritiated thymidine autoradiography demonstrated that considerable growth in culture was possible. Addition of heparin and endothelial cell growth supplement to the medium enhanced proliferation. The endothelial origin of the cultured cells was confirmed by immunofluorescent demonstration of the presence of Factor VIII-related antigen and angiotensin-converting enzyme. In addition, tight junctions between cells were observed in both thin sections and platinum replicas obtained by freezefracture techniques. Endothelial cells from neither the stria vascularis nor the spiral ligament allowed passage of horseradish peroxidase across the monolayer during a 5-min period. However, endothelial cells from the stria vascularis exhibited a greater amount of pinocytotic activity than those of the spiral ligament, a difference that is also observed in vivo. Methods for expanding a small population of endothelial cells with retention of specialized properties into one of sufficient size for morphologic and biochemical studies have been demonstrated for the inner ear.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47680/1/441_2004_Article_BF00214566.pd

Comparative ototoxicity of gentamicin in the guinea pig and two strains of rats

Gentamicin ototoxicity and nephrotoxicity were compared in two strains of rats. Sprague-Dawley and Fisher-344, and in the Hartley albino guinea pig. Treatment groups consisting of 8 male rats of each strain and four male guinea pigs were dosed subcutaneously for 14 days with either 80 or 100 mg/kg of gentamicin sulfate in saline. Brainstem auditory evoked response (BAER) thresholds were recorded from each animal in each group on day 11 post-administration. Blood urea-nitrogen and serum creatinine were measured in blood obtained on day 11 post-administration as measures of nephrotoxicity. Kidney weight/body weight ratios were also determined. Loss of sensory hair cells was observed in the basal region of the organ of Corti from all animals treated with 100 mg/kg of gentamicin. The hair cell loss and BAER threshold elevations were greatest in the guinea pigs. Fisher-344 rats showed more extensive hair cell loss and greater BAER threshold elevations than Sprague-Dawley rats. The Fisher-344 rats exhibited increased blood urea-nitrogen and kidney weight/body weight ratios. Sprague-Dawleys did not suffer any nephrotoxic effects. These data indicate that the Fisher-344 rat is a useful animal in which to study aminoglycoside ototoxicity as it exhibits both functional and morphological changes after gentamicin administration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26478/1/0000014.pd

Resident and Faculty Feedback: The Student’s Perspective

Background Feedback from faculty members and residents is a critical component of undergraduate medical education. Little is known about how students assess the adequacy of feedback from faculty and residents. Purpose To report medical students’ evaluations of clinical teacher feedback and to determine if students assess feedback given by residents differently than they assess feedback given by faculty. Methods Data were retrospectively collected from medical students’ responses to end-of-clerkship questionnaire items that evaluated feedback from residents and attending physicians. The mean ratings of faculty feedback in four clerkships were compared with the mean ratings of resident feedback within each academic year from 1998 to 2002