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Biomedical subjects

C A Schaffer

Publications and source records attributed to C A Schaffer.

7 recordsLinked to original sources

Effects of sample size on the latency and amplitude of the auditory evoked response.

Experiment I investigated the effects of sample size (500 to 1500 stimulus repetitions) on the auditory brainstem response as a function of intensity (20 to 80 dB nHL) on a group of 10 normally hearing subjects. There was little change in identifiability, reliability, latencies, or amplitudes of Waves I, III, and V as the sample size increased from 500 or 750 to 1500 repetitions. These results suggest that 500 to 750 repetitions may be adequate when methods similar to those in the present study are used, and that the common clinical practice of employing approximately 1500 repetitions may unnecessarily prolong testing. Experiment II employed 12 hearing-impaired subjects who were tested at 10 to 40 dB SL using sample sizes from 250 to 4500 stimulus repetitions. Identifiability of all waves increased as sample size increased from 250 to 4500 repetitions. The largest changes in identifiability occurred when sample size increased from 250 to 1500 or 3000 repetitions, with little improvement as sample size increased from 3000 to 4500 repetitions. Examiners should monitor averaged responses and terminate testing as soon as a wave is identified. Contrary to expectation, there was no systematic change in the standard error of measurement for latency (approximately 0.07 ms) as sample size increased from 250 to 4500 repetitions. The standard error of measurement for amplitude decreased from approximately 100 nV with 500 repetitions to approximately 45 nV at 3000 repetitions. The improvement in reliability with increasing sample size may be explained by a decrease in the variability of background noise. A systematic decrease in amplitude also was observed as sample size increased. This observation may be explained by a reduction in the residual noise levels or because of time jitter or adaptation within the auditory pathways. Nonetheless, investigators who wish to use ABR amplitude measures for diagnosis may benefit from using a relatively large sample size.

Adult↗

Late auditory evoked potentials can occur without brain stem potentials.

The sequence of early, middle and late auditory evoked potentials is well known. However, it is unknown whether the late (60-250 msec) potentials can occur independently of the early, brain stem potentials. Therefore, in 6 subjects with markedly abnormal or absent brain stem potentials, we recorded two of the late potentials: the vertex potential and the T-complex. The latter is a putative product of auditory cortex. Both of these potentials were clearly evident in all patients in spite of the absence of or marked abnormalities in brain stem potentials.

Brain Stem↗

Retinal blood flow derived from dye dilution curves: Televised fluorescein angiography.

A television system was used to record retinal fluorescein dilution curves. In pigs, fluorescein was injected intravenously (IV), into the left ventricle (ILV), and ILV during bilateral carotid occlusion (ILVco). Dye dilution curves from points on a retinal-artery-vein pair, from two points on a single artery, and from two points on a single vein were recorded by a storage oscilloscope, using two photodetectors positioned over the television image of the vessels. Dye curves were less dispersed following ILV than following IV injections, and were irregular following ILVco injection. The dye appearance time was shortest after injection with ILV and progressively longer with ILVco and IV. The artery-vein mean transit time was greatest during carotid occlusion. Retinal blood flow in a venous segment was calculated to be 0.149 +/- 0.037 mi/min. This value was reproducible following both IV and ILV injections but could not be obtained following ILVco due to irregularity of the curves. It was in the same range as that found (0.095 +/- 0.011 ml/min), using the radioactively labeled microsphere technique. The system was subsequently tested in humans and was found to give reproducible dye curves. The usefulness of the system as a clinical tool is presently being explored.

Animals↗

Techniques of EEG frequency analysis for evaluation of uremic encephalopathy.

In an effort to provide nephrologists with practical, objective, and quantitative methods for evaluating uremic encephalopathy and the severity of uremia, we investigated five techniques for EEG frequency analysis, the selection of EEG samples for analysis, and the normal values for dominant frequency and the percent of EEG power from one through six Hz. The five techniques consisted of 1. handcounting, 2. use of a tape recorder and sonic analysis system to determine EEG power versus frequency, 3. use of the tape recorder and sonic analysis system to determine EEG voltage versus frequency, 4. on-line measurement of % EEG voltage from one through six Hz, and 5. use of base line crossovers to count the number of waves occurring at each frequency. All techniques were found to be satisfactory. The most significant difference between techniques depended on whether wave amplitude influenced the analysis (techniques 2, 3, and 4) or did not (techniques 1 and 5); in the former case slow wave activity was more evident than in the latter case. Our experience indicated that the determination of relative EEG power from each frequency (EEG power versus frequency or power spectral density) was the most practical and revealing mode of analysis, but any of these techniques would be valid and useful if employed with awareness of the difference in the normal range obtained by different techniques.

Brain Diseases↗

Fluidized-bed receptor-affinity chromatography.

A multipurpose fluidized-bed receptor-affinity purification system based upon the biological recognition between an immobilized receptor and its soluble protein ligands is described. The fluidized affinity sorbent consists of a soluble form of interleukin-2 receptor chemically bonded to an aldehyde derivative of controlled pore glass beads, which have a pore diameter of 1000 A and a particle density of 1.2-1.3 g/mL. The fluidized-bed separation device used in this study consists of a specially designed column fitted at the inlet end with a perforated distributor plate covered with a screen and the top outlet with an adjustable piston. The fluidized-bed consisting of a loose gel matrix permits the unimpeded passage of cell debris and particulate matter, while the target protein is captured by the affinity beads. Purification of the humanized-anti-Tac monoclonal antibody is used as a model system to determine the operational parameters. Also, fluidized-bed receptor-affinity chromatography has been successfully employed in the purification of recombinant interleukin-2 and single chain anti-Tac(Fv)-Pseudomonas exotoxin immunotoxin from unclarified inclusion body extracts. Overall, fluidized-bed receptor-affinity chromatography is found to be a productive affinity method suitable for the purification of recombinant human interleukin-2 and related molecules.

ADP Ribose Transferases↗

Rational design of a potent, long-lasting form of interferon: a 40 kDa branched polyethylene glycol-conjugated interferon alpha-2a for the treatment of hepatitis C.

A potent, long-lasting form of interferon alpha-2a mono-pegylated with a 40 kilodalton branched poly(ethylene glycol) was designed, synthesized, and characterized. Mono-pegylated interferon alpha-2a was comprised of four major positional isomers involving Lys31, Lys121, Lys131, and Lys134 of interferon. The in vitro anti-viral activity of pegylated interferon alpha-2a was found to be only 7% of the original activity. In contrast, the in vivo antitumor activity was severalfold enhanced compared to interferon alpha-2a. Pegylated interferon alpha-2a showed no immunogenicity in mice. After subcutaneous injection of pegylated interferon alpha-2a, a 70-fold increase in serum half-life and a 50-fold increase in mean plasma residence time concomitant with sustained serum concentrations were observed relative to interferon alpha-2a. These preclinical results suggest a significantly enhanced human pharmacological profile for pegylated interferon alpha-2a. Results of Phase II/III hepatitis C clinical trials in humans confirmed the superior efficacy of pegylated interferon alpha-2a compared to unmodified interferon alpha-2a.

Animals↗