Letter, 1948 November 3, from M. J. Lihahan to Charles Hasin

2 pages, Linahan made reservations for Carson at Hotel Westbrook, Buffalo, New Yor

In Vitro Antitumour Activity of Some Triorganophosphinegold(I) Thionucleobases

A series of phosphinegold(I) thionucleobase analogues, [R3PAu(SRx)] (R = Et, Ph or chexyl; HSR1 = 2-mercaptobenzoic acid, HSR2 = 2-thiouracil, HSR3 = 6-mercaptopurine and HSR4 = 6-thioguanine) have been examined for their in vitro cytotoxicity in L1210 murine leukemia cells in culture. The range of ID50 values (continuous 48 h exposure) for the complexes is 0.041 - 0.131 μM. The complexes with SR3 and SR3 are generally the most active; however, there is no clear trend associated with the phosphine ligands

New Young Star Candidates in BRC 27 and BRC 34

We used archival Spitzer Space Telescope mid-infrared data to search for young stellar objects (YSOs) in the immediate vicinity of two bright-rimmed clouds, BRC 27 (part of CMa R1) and BRC 34 (part of the IC 1396 complex). These regions both appear to be actively forming young stars, perhaps triggered by the proximate OB stars. In BRC 27, we find clear infrared excesses around 22 of the 26 YSOs or YSO candidates identified in the literature, and identify 16 new YSO candidates that appear to have IR excesses. In BRC 34, the one literature-identified YSO has an IR excess, and we suggest 13 new YSO candidates in this region, including a new Class I object. Considering the entire ensemble, both BRCs are likely of comparable ages, within the uncertainties of small number statistics and without spectroscopy to confirm or refute the YSO candidates. Similarly, no clear conclusions can yet be drawn about any possible age gradients that may be present across the BRCs.Comment: 54 pages, 19 figures, accepted by A

Chronic monopolar high rate simulation of the auditory nerve: physiological and histopathological effects

There is clinical interest in the development of high rate speech processing strategies, since there are indications that these might enhance speech perception due to an improved representation of the rapid variations in amplitude of speech. Significant improvement in speech perception using high rate stimulation has been demonstrated in cochlear implant recipients. However, it is important that the long-term safety of high rate stimulation is clearly established prior to its general clinical application. This is especially important, since acute animal studies have shown that high rate stimulation can induce a reduction in the excitability of the auditory nerve. This was also associated with an increase in both threshold and latency of the electrically evoked auditory brainstem response (EABR). However, while a chronic stimulation study indicated that monopolar electrical stimulation of the auditory nerve at rates of 1000 pulses per second (pps)/channel (three channels) had no adverse effects on the spiral ganglion cell density (SGCO),5 there is limited data concerning higher rates. In the present study, we evaluated the electrophysiological and histopathological effects of chronic monopolar electrical stimulation of the auditory nerve using considerably higher stimulus rates than have been used in previous studies.5-7 Apri

Physiological and histopathological effects of chronic monopolar high rate stimulation of the auditory nerve [Abstract]

Speech processing strategies based on high rate electrical stimulation have been associated with improvements in speech perception among cochlear implant users. The present study was designed to evaluate the electrophysiological and histopathological effects of long-term intracochlear monopolar stimulation at the maximum stimulus rate of the current Nucleus Cochlear implant system (14493 pulses/s) as part of our ongoing investigations of safety issues associated with cochlear implants.29 August - 3 Septembe

Electrical stimulation of the auditory nerve: chronic monopolar stimulation using very high stimulus rates [Abstract]

Abstract of Poster 137This is an abstract of a poster presentation from the Proceedings of the Australian Neuroscience Society 1998. This version is reproduced with the permission of the publisher.Speech processing strategies based on high rate electrical stimulation have been associated with recent improvements of speech perception among cochlear implant users. In the present study we investigated the effects of chronic monopolar stimulation using very high rates (14493 pulses\s). Under general anaesthesia (ketamine (20 mg/kg) and xylazine (3.8 mg/kg) i.p.) six normal hearing cats were implanted bilaterally with a three channel platinum (Pt) scala tympani electrode array, while a return Pt-electrode was placed outside the bulla. Chronic electrical stimulation using charge-balanced biphasic current pulses was delivered unilaterally via a transcutaneous leadwire connected to a backpack-stimulator for up to 2000 h. The animals hearing status was periodically monitored using acoustically evoked compound action potentials (CAP's) and brainstem responses (ABR's). In addition the electrically evoked ABR (EABR) was also recorded to ensure that the chronic stimulus was above threshold. Stimulus current and electrode voltage waveforms were monitored twice daily and access resistance (Ra) and electrode impedance (Zc) calculated. ABR and CAP thresholds were elevated immediately following implantation, but generally showed evidence of partial recovery (0-40 dB). Further deterioration of thresholds on the stimulated side (10-30 dB) was subsequently observed, while control-thresholds remained more stable. Ra (1.3-1.8 kΩ) and Zc (2.2-3.8Ω) typically increased in the first few weeks of electrical stimulation up to Ra:5.6 kΩ and Zc:8.1 kΩ, before decreasing slightly to a constant plateau. These initial results indicate changes in the electrode-tissue interface and tissue growth within the cochlea. They also indicate that chronic stimulation at these high rates may decrease residual hearing.27-30 Januar

Physiological and histopathological effects of chronic monopolar high rate stimulation on the auditory nerve

Speech processing strategies based on high rate electrical stimulation have been associated with improvements in speech perception among cochlear implant users. The present study was designed to evaluate the electrophysiological and histopathological effects of long-term intracochlear monopolar stimulation at the maximum stimulus rate of the current Nucleus Cochlear implant system (14493 pulses/s) as part of our ongoing investigations of safety issues associated with cochlear implants4-7 Jun

Physiological and histopathological effects of chronic monopolar stimulation on the auditory nerve using very high stimulus rates [Abstract]

This is an abstract of a paper from the Proceedings of the Australian Neuroscience Society 1999 published by Australian Neuroscience Society. This version is reproduced with the permission of publisher.Speech-processing strategies using high stimulus rates are used in some cochlear implant systems. While some data suggests that electrical stimulation of the auditory nerve at rates of 2000 pps per channel is safe, there is little data concerning higher rates. The present study was designed to evaluate the safety of a rate of 5000 pps per channel. Under anaesthesia, (ketamine (20 mg/kg. i.v.) and xylazine (3.8 mg/kg. i.v.)), four normal hearing cats were bilaterally implanted with a three channel platinum (Pt) scala tympani electrode array and a return Pt-electrode placed within the temporalis muscle. Each animal was stimulated unilaterally for durations of up to 2700 h using 25μגs per phase charge-balanced biphasic current pulses. The stimuli were delivered at 5000 pps per channel at mid-dynamic range intensities. Acoustically-evoked auditory brainstem responses (ABRs) were recorded during the stimulation regime to monitor the animals' residual hearing. Electrically-evoked auditory brainstem responses (EABRs) were periodically recorded to monitor the status of the auditory nerve and to ensure stimulus intensity remained above threshold. ABRs typically showed poor recovery in the stimulated ear. Longitudinal EABRs recorded from all animals remained relatively stable for the duration of stimulation. Electrode impedances were calculated from daily monitoring of current and voltage waveforms. Two animals that exhibited the highest electrode impedance throughout the duration of stimulation were found to have significant amounts of new bone growth and fibrous tissue in the basal region of the cochlea. However, as one of these animals showed a similar response in the contralateral, unstimulated, implanted cochlea, this response can not be attributed to electrical stimulation per se. There was no statistically significant difference in spiral ganglion cell density in the stimulated cochleae when compared to corresponding regions in controls (p?0.2, Mann-Whitney Rank. Sum Test). These initial results indicate that chronic monopolar stimulation of the cochlea at a rate of 5000 pps per channel does not have an adverse effect on spiral ganglion cell density.31 January - 3 Februar

Chronic electrical stimulation of the auditory nerve using non-charge-balanced stimuli

Publisher’s permission requested and denied.This study was designed to evaluate the pathophysiological response of the cochlea following long-term intracochlear electrical stimulation using a poorly charge-balanced stimulus regime, leading to direct current (DC) levels >0.1 µA. Four normal-hearing adult cats were bilaterally implanted with scala tympani electrode arrays and unilaterally stimulated for periods up to 2200 h. Stimuli consisted of 50 µs monophasic current pulses presented at 2000 pulses per second (pps) per channel, and resulted in DC levels of 0.4-2.8 µA. Both acoustic and electrical (EABR) evoked potentials were periodically recorded during the stimulation program. Frequency-specific stimuli indicated that an extensive and widespread hearing loss occurred over the 4-24 KHz region in all stimulated cochleae, although the 2 KHz region exhibited thresholds close to normal in some animals, despite long-term implantation and chronic stimulation. Longitudinal EABRs showed a statistically significant increase in threshold for three of the four animals. Histopathological evaluation of the cochleae revealed a highly significant reduction in ganglion cell density in stimulated cochleae compared with their controls. Spiral ganglion cell loss was significantly correlated with the degree of inflammation, duration of electrical stimulation, and the level of DC. In conclusion, the present study highlights the potential for neural damage following stimulation using poorly charge-balanced stimuli

Chronic electrical stimulation of the auditory nerve using non-charge balanced stimuli [Abstract]

Abstract of Poster 138This is an abstract of a poster presentation from the Proceedings of the Australian Neuroscience Society 1998. This version is reproduced with the permission of the publisher.Cochear implants use charge balanced biphasic current pulses and electrode shorting between current pulses to minimise potentially damaging direct current (DC). In the present study we evaluated the effectiveness of the electrode shorting technique using a non-charge balanced stimulus regime. Under general anaesthesia (ketamine (20 mg/kg. i.m.) and xylazine (3.8 mg/kg. i.m)), eight normal hearing cats were bilaterally implanted with two channel platinum scala tympani electrodes. Each animal was stimulated unilaterally for 500 to 2200 h using 50 μs monophasic current pulses. The stimuli were delivered at rates of 500 or 2000 pulses per channel continuously at mid-dynamic range intensities. Electrically-evoked auditory brainstem responses (EABR) were periodically recorded to monitor the status of the auditory nerve and to ensure stimulus intensity remained above threshold. At a stimulus rate of 500 pulses/s, electrode shorting effectively reduced DC levels to ≤ 0.3µA. Longitudinal EABR's recorded from these animals , remained relatively stable over the stimulus duration. These cochleae showed minimal tissue response and there was no statistically significant difference in spiral ganglion cell density when compared with controls (p=0.21, Mann-Whitney U-test). Chronic stimulation at 2000 pulses/s resulted in increased DC levels (0.6-2.8µA). These cochleae exhibited a highly significant reduction in spiral ganglion cell density when compared with controls (p<0.0001), and their EABR's typically displayed an elevation in threshold as a function of stimulus duration. The present findings indicate that continuous non-charge balanced stimuli at rates of 2000 pulses/s can result in significant loss of spiral ganglion cells, presumably as a result of increased DC levels.27-30 Januar