Two-component hearing sensations produced by two-electrode stimulation in the cochlea of a deaf patient.

Dissimilarities in perception elicited by stimulation with two electrodes were estimated. A two-dimensional spatial configuration was found to be suitable to represent the dissimilarity data, and the two dimensions could be interpreted as corresponding to the position of the apical and basal electrode of the two-electrode combination. A speech-processing strategy that converts acoustic, first and second formants to two-electrode stimulation is proposed.

Selenium status in Southern Tasmania.

OBJECTIVE: To assess the selenium status of Southern Tasmanians. DESIGN: Cross-sectional. SETTINGS: One thousand and five hundred adults randomly selected from the electoral roll living in the Greater Hobart region of Southern Tasmania, Australia, were invited to participate. SUBJECTS: The overall response rate was 22% (335/1500). INTERVENTIONS: A venous blood sample was collected and a questionnaire administered (consisting of brief demographic details and health questions) to subjects who granted informed consent. A previously validated assay using magnetic sector ICP-MS was employed for plasma analysis. RESULTS: Total plasma selenium levels for this sample population were normally distributed with a mean level of 110 microg/l (range 67-268 microg/l) indicating that the majority of the subjects were not selenium-depleted (71% with levels greater than 100 microg/l). Adjustment for differential age/gender response rates produced similar values. More women under 50 (42%) and men over 50 (32%) had selenium levels <100 microg/l with the potential for sub-optimal selenoprotein activity. Low education attainment was associated with low total selenium level (P<0.02). CONCLUSIONS: The majority of participants were not deficient in selenium. Given the narrow therapeutic window of supplementation, dietary advice to increase foods rich in selenium, particularly to higher risk groups, may be an effective means of increasing plasma selenium toward target levels.

Antipicornavirus activity of substituted phenoxybenzenes and phenoxypyridines.

Phenoxybenzenes and phenoxypyridines were prepared and tested for the effect of substituents on antipicornavirus activity. The most active compound, 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (8), demonstrated broad-spectrum antipicornavirus activity. Compound 8 and several analogues each given orally prior to and during infection protected mice against an otherwise lethal challenge with coxsackievirus A21.

Evaluation and validation of ureteric jet index by glomerular filtration rate.

RATIONALE AND OBJECTIVES: Ureteric jet index (UJI), a newly developed technique derived from color Doppler ultrasonography, may hold promise in evaluating renal function because of its ability to evaluate individual renal function and the use of nonionizing radiation. To assess the usefulness of UJI, the authors in this study analyzed the relation between UJI and the glomerular filtration rate (GFR). METHODS: Fifteen adult patients with a wide range of renal function were included in this study. Subjects were well hydrated before color Doppler ultrasonography examinations. The UJI formula was: Vmean (average jet velocity) x D (jet duration) x F (jet frequency). GFR was calculated by the radionuclide method. Correlations between UJI, serum creatinine, and GFR were analyzed. RESULTS: Ureteric jet index had only a fair correlation with GFR. The coefficient of correlation value was 0.61, and the standard error of estimate of GFR was 17.9 mL/min. CONCLUSIONS: With the measurement of UJI, color Doppler ultrasound can provide both structural images and individual renal function information. It could substitute for a renal scan in determining individual renal function when a radionuclide examination is unavailable. Even if a renal scan were available, UJI can play a valuable role in the ultrasound examination of patients with suspected impaired renal function, providing further assessment of individual renal function.

Percepts from scala tympani stimulation.

The characteristics of the sensations produced by activating one electrode at a time are summarized as follows: (a) Loudness was found to increase with current level and pitch with repetition rate. (b) Pitch and sharpness increased in the apical-to-basal direction, and vowel labels could be assigned to sensations produced by individual electrodes in accordance with the tonotopical organization of the cochlea. (c) Results from triadic comparisons provided evidence that the sensations produced by repetition rate and electrode position are perceptually separable. (d) For short-duration stimuli, the discrimination performance for electrode trajectories was much better than that for repetition rate trajectories. For noncoincidental two-electrode stimulation, triadic comparisons showed that two perceptual components, one related to the more basal electrode and the other to the more apical one, could be discerned. Speech-coding considerations based on these psychophysical results are discussed.

Current distributions in cochlear stimulation.

Animal experimental studies have shown length constants of 2-4 mm for bipolar and 8-16 mm for monopolar stimulations. Studies in models using saline-solution-filled tubes have allowed us to examine the radial and longitudinal current distribution for pseudobipolar stimulation and have demonstrated that current localization is the same for bipolar and pseudobipolar stimulation over a 6-10-dB operating range. With coincident pseudobipolar multiple-channel stimulation there was suppression of the current between the stimulus maxima and enhancement at the edges leading to less stimulus interaction. Experiments performed with a pseudobipolar electrode implanted into the human cochlea showed that there was significant spread of current along the ground electrode because the electrode ground impedance was significantly greater than the cochlear tissue impedances. Because this leads to less current returned at each ground electrode, the pseudobipolar array will result in less interaction for coincident stimulation.

Design and fabrication of the banded electrode array.

The banded electrode array is a simple and effective array for multiple-channel cochlear stimulation and meets the necessary design requirements.

Subtyping of alpha1-adrenoceptors responsible for the contractile response in the rat corpus cavernosum.

The subtyping of alpha1-adrenoceptors responsible for mediating contraction in isolated corpus cavernosum of mature male Wistar rats was studied pharmacologically. Concentration-response studies of the cavernosal smooth muscle to three agonists: methoxamine, norepinephrine and octopamine showed that methoxamine exhibited the highest potency in inducing contractile response; the respective pD2 values were: 6.22, 5.83 and 5.38. In the presence of 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB4101), a specific antagonist for alpha1A-adrenoceptors, a parallel rightward shift of the concentration-response curve to methoxamine was observed. On the other hand, chloroethylclonidine (CEC) caused a rightward shift of the concentration-response curve to methoxamine with significant suppression of the maximum response. The pA2 value for WB4101 obtained from Schild plot was 9.03 +/- 0.06 with slope (95% CL) equal to 0.955 (1.088-0.832). In the absence of extracellular calcium ions, the methoxamine-induced contraction was reduced by 92%. Ca2(+)-Channel blockers, nifedipine 10(-6) M and diltazem 10(-6) M decreased the contractile response by 18 and 23%, respectively. The present findings suggest that alpha1A-adrenoceptors are responsible for the methoxamine-induced contraction of the rat cavernosal smooth muscle.

Evidence of P2Y-purinoceptor mediated bladder neck smooth muscle post-contractile relaxation in the male mini-pig.

The functional role of non-adrenergic non-cholinergic (NANC) nerves in the autonomic control of the male mini-pig bladder neck was investigated in the present study. Electrical stimulation of muscle strips from male mini-pig bladder neck showed biphasic response with initial phasic contraction followed by post-contractile relaxation. Electrical stimulation in the presence of four autonomic blockers (atropine 10(-6) M, propanolol 10(-6) M, phentolamine 10(-6) M) showed suppression of 68 +/- 15% of the contractile response (P < 0.05, n = 8) but no significant change in the relaxation response. Alpha-chymotrypsin 2 U/ml, L-NG-monomethyl-L-arginine acetate (a nitric oxide synthetase inhibitor) 10(-4) M, 8-phenylthlophylline (a P1-purinoceptor antagonist) 10(-6) M, and pyridoxal-phosphate-6-azophenyl-2', 4'-disulphoric acid tetrasodium salt (a P2Y-purinoceptor antagonist) 3 x 10(-5) M did not alter the NANC response significantly. On the other hand, reactive blue-2 (a P2Y-purinoceptor antagonist) 3 x 10(-5) significantly reduced the relaxation by 79 +/- 9%. The result suggested that the P2Y-purinoceptor is involved in the electrically induced NANC post-contractile relaxation of the mini-pig bladder neck smooth muscle.

The role of nitric oxide in the control of plasma glucose concentration in spontaneously hypertensive rats.

Glucose homeostasis was studied in the spontaneously hypertensive rat (SHR). The fasting plasma glucose levels were similar in the SHR and normotensive Wistar-Kyoto (WKY) rat (102.7+/-2.4 vs. 107.4+/-4.2 mg/dl, P > 0.01). One hour after glucose challenge, the plasma glucose level was slightly but insignificantly increased in both SHR and WKY rat (117+/-2.5 vs. 114.3+/-3.2 mg/dl, P > 0.01). After N(G)nitro-L-arginine methyl ester (L-NAME) 20 mg/kg per day was administered intraperitoneally (i.p.) for 4 days, the plasma glucose level was significantly increased in the rats (SHR 167.3+/-4.9; WKY rat 136.0+/-4.8 mg/dl); the increase was significantly more pronounced in the SHR. The fasting insulin levels were similar in the SHR and WKY rats (2.3+/-0.4 vs. 2.0+/-0.3 ng/ml, P > 0.01). One hour after glucose challenge, the insulin level was significantly increased in the WKY rat (4.8+/-0.7 ng/ml) but not in the SHR (2.2+/-0.4 ng/ml). With L-NAME treatment, plasma insulin increase was noted in the WKY rat but not SHR (4.6+/-0.6 vs. 2.6+/-0.4 ng/ml, n = 8, P < 0.01). One hour after insulin 1 IU/kg was injected intramuscularly (i.m.), the plasma glucose level was significantly decreased in both the SHR (from 115.0+/-6.5 to 48.6+/-3.6 mg/dl, n = 8) and WKY rat (from 108.3+/-3.8 to 52.6+/-4.2 mg/dl, n = 8). No significant difference was noted between the decrease of the two groups (P > 0.01). The present findings suggested that NO plays a role in the glucose homeostasis of rats. NO-synthase blockade resulted in an increase of plasma glucose level. The SHR maintains normal glucose level and tolerance in spite of a defective insulin release response. This is probably due the compensatory effect of a more prominent NO-dependent glucose homeostatic function.

Alterations in urinary bladder M2-muscarinic receptor protein and mRNA in 2-week streptozotocin-induced diabetic rats.

The M2 receptor (M2-mAChR) is quantitatively the dominant muscarinic subtype in animal bladders. The alterations in its protein quantity and biosynthesis during diabetic cystopathy were investigated. Three-month-old male Wistar rats were divided into two groups: (1) 2-week-old diabetics; and (2) normoglycemic control rats. Diabetes was induced by single intravenous injection of 60 mg/kg streptozotocin. The amount of M2 receptor protein in the rat bladder body tissue was measured by Western immunoblotting using monoclonal antibodies. For determination of M2 muscarinic receptor mRNA in the bladder tissue, the method of Northern blotting was employed. The results of the Western immunoblotting showed that the amount of M2-mAChR protein in the diabetic bladder was significantly increased by 40.0 +/- 6.2% when compared with the control bladder (P < 0.05, n = 8). The Northern blotting demonstrated a 69.3 +/- 8.5% increase of the M2-mAChR mRNA in the diabetic bladder (P < 0.05, n = 8). The findings of the present study demonstrated an up-regulation of M2-mAChR biosynthesis in the diabetic urinary bladder. This phenomenon could lead to increased reactivity to acetylcholine and thus results in detrusor instability.

Comparisons of neurotransmitter concentrations in the synaptosomal preparation of the normotensive and hypertensive rat urinary bladder.

Synaptosome-rich fractions were prepared from tissue homogenate of the urinary bladder of the spontaneously hypertensive rat and normotensive Wistar-Kyoto rat by differential centrifugation (1000 x g, 17 000 x g and 100 000 x g) with discontinuous sucrose gradient. Synaptosomal acetylcholine, norepinephrine, epinephrine and dopamine were measured by the method of high-performance liquid chromatography. The respective neurotransmitter concentrations for the normotensive rats were 300.4 +/- 30.1, 962.8 +/- 58.5, 617.3 +/- 59.8, and 1354.8 +/- 144.2 pmol/mg synaptosomal protein. For the hypertensive rats, the acetylcholine concentration (203.8 +/- 23.0 pmol/mg protein) was significantly lower (P < 0.05), while the norepinephrine, epinephrine and dopamine concentrations (1459.0 +/- 180.3, 971.3 +/- 62.2, and 2161.0 +/- 243.4 pmol/mg protein, respectively) were significantly higher (P < 0.05 for all) than those of the normotensive rats. In conclusion, it has been demonstrated that the vesicle-bound catecholamines in the synaptosome-rich fraction of the urinary bladder were significantly increased in hypertensive rats. On the contrary, the synaptosomal acetylcholine concentration was significantly decreased. These findings are suggestive of increased sympathetic innervation and decreased parasympathetic innervation in the urinary bladder of the spontaneously hypertensive rat.

Alterations in urinary bladder synaptosomal neurotransmitter concentrations in two-week streptozotocin-induced diabetic rats.

Three-month-old male Wistar rats were rendered diabetic with a single intravenous injection of streptozotocin (60 mg/kg body weight). Two weeks after induction of diabetes, synaptosome-rich fractions were prepared from urinary bladder tissue homogenate of the diabetic rats and control rats by differential centrifugation (1000 x g, 17,000 x g and 100,000 x g) with discontinuous sucrose gradient. Synaptosomal acetylcholine, norepinephrine, epinephrine and dopamine were measured by the method of high-performance liquid chromatography. The respective neurotransmitter concentrations for the diabetic rats were 1537.8 +/- 65.3, 4757.7 +/- 361.9, 3720.7 +/- 276.1, and 2447.8 +/- 196.8 pmol/mg synaptosomal protein, respectively; those for the control rats were 338.1 +/- 25.0, 1009.0 +/- 54.6, 645.3 +/- 52.2, and 1426.1 +/- 123.9 pmol/mg protein, respectively. Thus, the synaptosomal concentrations for all the measured neurotransmitters were significantly higher in the diabetic rats (P < 0.05 for each comparison). In conclusion, it has been demonstrated that the vesicle-bound acetylcholine and catecholamines in the synaptosome-rich fraction of the urinary bladder were significantly increased in 2-week diabetic rats. This finding would suggest impaired neurotransmitter release from both the bladder sympathetic and parasympathetic efferent nerve endings in early streptozotocin-induced diabetes.

Expression of nm23-H1 in transitional cell carcinoma of the upper urinary tract.

Transitional cell carcinoma of the upper urinary tract is an uncommon neoplasm. Relatively little information is available regarding the clinical relevance of molecular markers. This study was performed to examine the importance of nm23-H1 gene expression (NM23-H1) in this type of tumors. Immunohistochemical expression of NM23-H1 was analyzed in 90 cases of upper urinary tract cancer, and was compared for its prognostic significance with conventional biological indicators. High expression of NM23-H1 was found in 7 cases (8%), intermediate expression in 32 cases (36%), and low expression in 51 cases (57%). Reduced NM23-H1 (defined as intermediate or low level of expression) was associated with a higher histological grading (p=0.002), invasive tumor growth (p=0. 002), or an increased proliferating cell nuclear antigen labeling index (p=0.004). NM23-H1 tended to inversely relate to later recurrence or long-term survival (p=0.06), but, only tumor staging was found to be significant in predicting clinical outcome (p=0.002). nm23-H1 appears to function as a tumor suppressor for upper urinary tract cancer, however, evaluation of NM23-H1 provides limited prognostic information.

The expression of p53 and bcl-2 in superficial bladder transitional cell carcinoma and its role in the outcome of postoperative intravesical chemotherapy.

BACKGROUND: We evaluated whether p53 and bcl-2 expression has any predictive value on the outcome of postoperative adjuvant intravesical chemotherapy for superficial bladder transitional cell carcinoma (TCC). MATERIALS AND METHODS: Immunostaining for p53 and bcl-2 was performed on paraffin-embedded tumor tissues obtained from 100 patients with superficial bladder TCC. 56 had solitary and 44 had multiple tumors; 36 were grade I, 53 grade II and 11 grade III; 50 were stage pTa and 50 stage pT1. They all received transurethral resection (TUR) and weekly intravesical instillation chemotherapy with either Thiotepa (70 patients) or Epirubicin (30 patients) for consecutive 8 doses postoperatively. RESULTS: Overall, 7 (7%) tumors were p53+ and 12 (12%) tumors were bcl-2+. Of these, only one tumor was combined p53+ and bcl-2+. The status of tumor p53 and bcl-2 positivity was found to be not significantly correlated with either tumor grade or stage. After adjuvant intravesical chemotherapy, tumor recurrence is significantly correlated with tumor multifocality (p = 0.0002) but not with tumor grade and stage. Compared with p53- or bcl-2- tumors, patients with p53+ or bcl-2+ tumors do not show a higher tumor recurrence rate. The number of recurrence-free patients was also not significantly different in p53+ versus p53- tumors, bcl-2+ versus bcl-2- tumors. Six (6%) patients eventually developed disease progression, and none stained positively for either p53 or bcl-2. CONCLUSIONS: We conclude that in superficial bladder TCC the status of tumor p53 and bcl-2 expression is not correlated with stage and grade. Their expression, either alone or combined, has no predictive role on the outcome of post-TUR intravesical chemotherapy on tumor recurrence.

The clinical value of p21WAF1/CIP1 expression in superficial bladder cancer.

The clinical value of p21WAF1/CIP1 in superficial bladder cancer remains controversial. To address the question, we examined the expression patterns of p21 and p53 gene products and compared for their significance in a total of 89 cases of superficial (pTa/pT1) bladder cancer. Over-expression of p21 was detected in 32 of 89 (36%) tumors. But, the expression status did not correlate with biological indicators or clinical outcome (p > 0.1, respectively). Factors predicting clinical outcome were multiplicity for tumor recurrence (p = 0.0002) or patient survival (p = 0.03), and the histological grading for disease progression (p = 0.02) or patient survival (p = 0.05). Taking into account the p53 status, a trend approaching better prognosis for p53+p21+ tumors was observed compared with that of p53+p21- bladder cancer (p = 0.08). Our data indicate that evaluation of p21 status does not provide better prognostic information compared with conventional biological indicators of superficial bladder cancer. Maintenance of p21 appears to abrogate the deleterious effects of p53 alterations in the tumorigenesis of human bladder.

Prognostic significance of proliferating cell nuclear antigen expression in transitional cell carcinoma of the upper urinary tract.

BACKGROUND: Haphazard cell proliferation is a fundamental biologic defect in cancer. Thus, assessment of the growth fraction provides a valuable index of biological property for human neoplasm. Proliferating cell nuclear antigen (PCNA) expression has been used to estimate the growth fraction of human cancer, and its prognostic value. Information in transitional cell carcinoma (TCC) of the upper urinary tract, however, is very few. MATERIALS AND METHODS: A total of 73 patients with TCC of the upper urinary tract was collected between July 1988 and December 1995 for this study. The labeling index of PCNA immunostaining was correlated with clinicopathologic factors and compared for its prognostic value with a median follow-up of 54 months. RESULTS: The PCNA index was positively associated with histological grading, tumor stage and patient prognosis (P = 0.00, respectively). Multivariate analysis demonstrated that significant factors in relation to patient survival were tumor stage (P = 0.01), followed by PCNA index (P = 0.04) and gender of patients (P = 0.04). Multiple comparison revealed that PCNA index set at 0.30 had prognostic value in terms of patient survival (P = 0.00), and the risk of metachronous bladder recurrence (P = 0.02). CONCLUSION: Our data suggested that assessment of PCNA index may be used as an adjuvant prognostic factor for patients with TCC of the upper urinary tract.

Neural processes in the dorsal cochlear nucleus of the anaesthetised cat investigated from unit responses to electrical stimulation of the auditory nerve.

Extracellular responses of dorsal cochlear nucleus single units were recorded in response to biphasic, bipolar electrical stimulation of spiral ganglion cells and their peripheral processes using a banded electrode array in the scala tympani of the barbiturate anaesthetised cat. The DCN responses to this stimulus were the result of excitatory and suppressive (including inhibitory) processes. The excitatory responses from DCN units were usually within a range of 1.8-2.8 ms and these responses were probably the result of monosynaptic input from the auditory nerve. Latencies > 2.8 ms were most likely due to activation of di- and poly-synaptic pathways from auditory nerve fibres, except that latencies between 3.5-4.75 in hearing animals could have arisen from electrophonic mechanisms. Suppression of spontaneous activity was usually long acting, lasting > 70 ms following each pulse of the pulse train, but short acting suppression with a latency of 3.5-4.75 ms and a duration of < 10 ms was occasionally observed. These suppressive responses probably resulted from synaptic inhibitory input, but neural membrane properties may have contributed. In hearing animals, excitatory latencies within the range 1.8-5.2 ms were similar for units with different response area types or different PSTH patterns in response to acoustic CF tones or noise.

A multiple-channel cochlear implant: an evaluation using open-set CID sentences.

A multiple-channel cochlear implant and speech processor have been used in two postlingually deaf adult patients with a total hearing loss, to enable them to perceive varying degrees of running speech. The results have veen confirmed with open-set CID everyday sentence tests. Using the implant alone, the patients obtained 8% and 14% scores with prerecorded material, and 34% and 36% scores for "live" presentations. This was equivalent to the perception of 35% of connected discourse. When the implant was used in conjuction with lipreading, improvements of 188% and 386% were obtained over lipreading alone, and the scores were 68% and 98% which were equivalent to the perception of 60% and 95% of connected discourse.

A multiple-electrode intracochlear implant for children.

A multiple-electrode intracochlear implant that provides 21 stimulus channels has been designed for use in young children. It is smaller than the adult version and has magnets to facilitate the attachment of the headset. It has been implanted in two children aged 5 and 10 years. The two children both lost hearing in their third year, when they were still learning language. Following implantation, it was possible to determine threshold and comfortable listening levels for each electrode pair. This was facilitated in the younger child by prior training in scaling visual and electrotactile stimuli. Both children are regular users of the implant, and a training and assessment program has been commenced.