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Biomedical subjects

W H Martin

Publications and source records attributed to W H Martin.

At least 19 recordsLinked to original sources

FDG PET and dual-head gamma camera positron coincidence detection imaging of suspected malignancies and brain disorders.

UNLABELLED: The purpose of the study was to compare the diagnostic accuracy of fluorodeoxyglucose (FDG) images obtained with a dual-head coincidence gamma camera (DHC) with those obtained with a dedicated PET in a series of 26 patients. METHODS: Nineteen patients with known or suspected malignancies and 7 patients with neurological disorders underwent PET imaging after injection of approximately 10 mCi of FDG. Whole-body imaging was performed on 19 patients and brain imaging on 7 patients. DHC images were then acquired for 30 min over the region of interest using a dual-head gamma camera equipped with 3/8-in.-thick NaI(TI) crystals and parallel slit-hole collimators. The images were reconstructed in the normal mode, using photopeak/photopeak, photopeak/Compton and Compton/photopeak coincidence events. RESULTS: Although the spatial resolutions of PET with a dedicated PET scanner and of DHC are in the same range, the lesion detectability remains superior with PET (4 mm for PET versus 13.5 mm for DHC in phantom experiments) with a contrast ratio of 5:1. This is most probably attributable to the higher sensitivity of PET (2238 coincidences/min/microCi for PET versus 89 coincidences/min/microCi for DHC). The pattern of uptake and interpretation for brain imaging was similar on both PET and DHC images in all patients. In the 19 oncology patients, 38 lesions ranging from 0.7 to 5 cm were detected by PET. DHC imaging detected 28 (73%) of these lesions. Among the 10 lesions not seen with DHC, 5 were less than 1.2 cm, 2 were located centrally within the liver and suffered from marked attenuation effects and 3 were adjacent to regions with high physiological activity. The nondetectability of some lesions with DHC compared with PET can be explained by several factors: (a) start of imaging time (mean+/-SD: 73+/-16 min for PET versus 115+/-68 min for DHC, leading to FDG decay to 6.75 mCi for PET and 5.2 mCi for DHC); (b) limited efficiency of a 3/8-inch-thick Nal(TI) crystal to detect 18F photons; (c) suboptimal two-dimensional reconstruction algorithm; and (d) absence of soft-tissue attenuation correction for centrally located lesions. CONCLUSION: FDG DHC imaging is a promising technique for oncological and brain imaging.

Adult

Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo.

An inhibitor of human liver glycogen phosphorylase a (HLGPa) has been identified and characterized in vitro and in vivo. This substance, [R-(R*, S*)]-5-chloro-N-[3-(dimethylamino)-2-hydroxy-3-oxo-1-(phenylmethyl)pr opyl]-1H-indole-2-carboxamide (CP-91149), inhibited HLGPa with an IC50 of 0.13 microM in the presence of 7.5 mM glucose. CP-91149 resembles caffeine, a known allosteric phosphorylase inhibitor, in that it is 5- to 10-fold less potent in the absence of glucose. Further analysis, however, suggests that CP-91149 and caffeine are kinetically distinct. Functionally, CP-91149 inhibited glucagon-stimulated glycogenolysis in isolated rat hepatocytes (P < 0.05 at 10-100 microM) and in primary human hepatocytes (2.1 microM IC50). In vivo, oral administration of CP-91149 to diabetic ob/ob mice at 25-50 mg/kg resulted in rapid (3 h) glucose lowering by 100-120 mg/dl (P < 0.001) without producing hypoglycemia. Further, CP-91149 treatment did not lower glucose levels in normoglycemic, nondiabetic mice. In ob/ob mice pretreated with 14C-glucose to label liver glycogen, CP-91149 administration reduced 14C-glycogen breakdown, confirming that glucose lowering resulted from inhibition of glycogenolysis in vivo. These findings support the use of CP-91149 in investigating glycogenolytic versus gluconeogenic flux in hepatic glucose production, and they demonstrate that glycogenolysis inhibitors may be useful in the treatment of type 2 diabetes.

Amides

Evaluation of benign vs malignant hepatic lesions with positron emission tomography.

BACKGROUND: In most malignant cells, the relatively low level of glucose-6-phosphatase leads to accumulation and trapping of [18F]fluorodeoxyglucose (FDG) intracellularly, allowing the visualization of increased uptake compared with normal cells. OBJECTIVES: To assess the value of FDG positron emission tomography (PET) to differentiate benign from malignant hepatic lesions and to determine in which types of hepatic tumors PET can help evaluate stage, monitor response to therapy, and detect recurrence. DESIGN: Prospective blinded-comparison clinical cohort study. SETTING: Tertiary care university hospital and clinic. PATIENTS: One hundred ten consecutive referred patients with hepatic lesions 1 cm or larger on screening computed tomographic (CT) images who were seen for evaluation and potential resection underwent PET imaging. There were 60 men and 50 women with a mean (+/-SD) age of 59 +/- 14 years. Follow-up was 100%. INTERVENTIONS: A PET scan using static imaging was performed on all patients. The PET scan imaging and biopsy, surgery, or both were performed, providing pathological samples within 2 months of PET imaging. All PET images were correlated with CT scan to localize the lesion. However, PET investigators were unaware of any previous interpretation of the CT scan. MAIN OUTCOME MEASURES: Visual interpretation, lesion-to-normal liver background (L/B) ratio of radioactivity, and standard uptake value (SUV) were correlated with pathological diagnosis. RESULTS: All (100%) liver metastases from adenocarcinoma and sarcoma primaries in 66 patients and all cholangiocarcinomas in 8 patients had increased uptake values, L/B ratios greater than 2, and an SUV greater than 3.5. Hepatocellular carcinoma had increased FDG uptake in 16 of 23 patients and poor uptake in 7 patients. All benign hepatic lesions (n = 23), including adenoma and fibronodular hyperplasia, had poor uptake, an L/B ratio of less than 2, and an SUV less than 3.5, except for 1 of 3 abscesses that had definite uptake. CONCLUSIONS: The PET technique using FDG static imaging was useful to differentiate malignant from benign lesions in the liver. Limitations include false-positive results in a minority of abscesses and false-negative results in a minority of hepatocellular carcinoma. The PET technique was useful in tumor staging and detection of recurrence, as well as monitoring response to therapy for all adenocarcinomas and sarcomas and most hepatocellular carcinomas. Therefore, pretherapy PET imaging is recommended to help assess new hepatic lesions.

Adolescent

Plasma glucose levels are reduced in rats and mice treated with an inhibitor of glucose-6-phosphate translocase.

The activity of glucose-6-phosphatase (G-6-Pase) in isolated rat microsomes was inhibited by a new selective inhibitor of the multi-subunit G-6-Pase system, 1-[2-(4-chloro-phenyl)-cyclopropylmethoxy]-3,4-dihydroxy-5-(3-imid azo[4,5-b]pyridin-1-yl-3-phenyl-acryloyloxy)-cyclohexanecarboxylic acid (compound A) with a 50% inhibitory concentration (IC50) of approximately 10 nmol/l. Compound A (500 nmol/l) inhibited the uptake of [14C]glucose-6-phosphate (G-6-P) into intact isolated rat microsomes, confirming that this agent blocks G-6-P translocation, as suggested by previous studies using intact and permeabilized microsomes. The inhibition of microsomal G-6-P transport by compound A was associated with inhibition of the rate of glucose output from rat hepatocytes incubated in the presence of 25 nmol/l glucagon (IC50 approximately 320 nmol/l.) Compound A (1 micromol/l) also inhibited the basal rate of glucose production by rat hepatocytes by 47%. Intraperitoneal administration of compound A to fasted mice lowered circulating plasma glucose concentrations dose-dependently at doses as low as 1 mg/kg. This effect was comparatively short-lived; glucose lowering was maximal at 30 min after dosing with 100 mg/kg compound A (-71%) and declined thereafter, being reversed within 3 h. A similar time course of glycemic response was observed in fasted rats; glucose lowering was maximal 30 min after dosing with 100 mg/kg compound A (-36%) and declined until the effect was fully reversed by 3 h postdose. In rats subjected to compound A treatment, liver glycogen content was increased. G-6-P and lactate levels were maximally elevated 30 min after dosing and declined thereafter. Cumulatively, these results suggest that the mechanism of glucose lowering by compound A was via inhibition of G-6-Pase activity, mediated through inhibition of the T1 subunit of the microsomal G-6-Pase enzyme system. Drug levels measured over the same time course as that used to assess in vivo efficacy peaked within 30 min of administration, then declined, which is consistent with the transient changes in plasma glucose and liver metabolites.

Animals

Fluorine-18-fluorodeoxyglucose cardiac imaging using a modified scintillation camera.

Conventional 201TI and hexakis 2-methoxy-2-isobutyl isonitrile studies are less accurate as compared to FDG PET in the prediction of functional recovery after revascularization in patients with injured but viable myocardium. The introduction of a dual-head variable-angle-geometry scintillation camera equipped with thicker crystals (5/8 in.) and high-resolution, ultrahigh-energy collimators capable of 511 keV imaging has permitted FDG SPECT to provide information equivalent to that of PET for the detection of injured but viable myocardium in patients with chronic ischemic heart disease. The development of standardized glucose-loading protocols, including glucose-insulin-potassium infusion and the potential use of nicotinic acid derivatives, has simplified the method of obtaining consistently good-to-excellent quality FDG SPECT cardiac studies. FDG SPECT may become the modality of choice for evaluating injured but viable myocardium because of enhanced availability of FDG, logistics, patient convenience, accuracy and cost-effectiveness compared to PET.

Equipment Design

A simplified intravenous glucose loading protocol for fluorine-18 fluorodeoxyglucose cardiac single-photon emission tomography.

The myocardial uptake of fluorine-18 fluorodeoxyglucose (FDG) has emerged as the most sensitive and specific technique for the assessment of myocardial viability. With the development of FDG single-photon emission tomography (SPET) and dual head coincidence imaging, a hindrance to the widespread clinical use of FDG cardiac imaging is the complexity of the preinjection glucose loading necessary for obtaining interpretable myocardial FDG scans. In a population of 209 patients undergoing dual-isotope single acquisition (DISA) FDG/sestamibi (MIBI) SPET, we describe the improvements in both image quality and time efficiency using a new short, simple glucose/insulin/potassium (GIK) infusion protocol prior to FDG injection as compared to a conventional oral glucose loading protocol. DISA FDG/MIBI SPET scans were performed in 111 nondiabetic patients after oral loading with 50 g of glucose (group 1). Ninety-eight consecutive nondiabetic patients were subsequently scanned following preparation with a fixed-concentration GIK infusion administered at a standardized rate (group 2). A three-point grading scale was used to assess image quality. The time to FDG injection following glucose administration was significantly shorter for the group 2 patients (39.9+/-15.6 min; range 20-105 min) than for the group 1 patients (99.5+/-30.3 min; range 56-270 min) (P<0.0001), representing a 1-h decrease in patient preparation time. More of the group 1 patients (n=30; 27%) required supplemental intravenous boluses of regular insulin than did the group 2 patients (n=13; 13%) (P<0.02). There were more excellent and good quality graded images using the GIK method (group 2) than the more traditional oral loading protocol (group 1) (P<0.02). Nine of 111 scans (8%) in group 1 were uninterpretable, whereas only one of 98 scans (1%) in group 2 was uninterpretable. Standardized infusion of a fixed concentration of GIK prior to FDG administration and continued during myocardial FDG uptake is an effective yet simple method of obtaining consistently good to excellent quality FDG SPET cardiac scans. It is preferable to conventional oral glucose loading due to decreased patient preparation time and improved image quality. The technique is safe and should improve both the clinical use and the cost-effectiveness of FDG SPET imaging for the identification of injured but viable myocardium.

Case-Control Studies

Effect of endurance training on fatty acid metabolism during whole body exercise.

Endurance exercise training increases fat oxidation during large muscle mass exercise. Although the source of this fat has been thought to be plasma free fatty acids (FFA) released from adipose tissue, the training-induced decrease in lipolytic hormonal responses to exercise is not consistent with this concept. The purpose of this communication is to review findings, from our laboratory indicating that, in young healthy subjects, endurance exercise training reduces plasma FFA turnover and oxidation during moderate intensity prolonged 2-leg cycling while simultaneously enhancing depletion of triglycerides from the active musculature. Evidence is presented that metabolism of intramuscular triglycerides can explain the increase in total fat oxidation observed in the trained state during large muscle mass exercise. However, these results may not be applicable to exercise involving small muscle groups, a distinction that is likely to be important in explaining the apparent conflict between our findings and those from other laboratories where experimental conditions were different. In summary, for large muscle mass exercise up to 2 h in duration, plasma FFA are a less important fuel source in the trained state, and intramuscular triglycerides supply the major portion of the increase in oxidized fatty acids.

Adult

ABR and DPOAE detection of cochlear damage by gentamicin.

Auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE) have been applied to the evaluation of peripheral auditory function. To date, no comparison of their relative sensitivities to aminoglycoside toxicity has been reported. The purpose of this study was to compare click evoked ABR testing and 2f1-f2 DPOAEs as detectors of cochlear damage induced by gentamicin treatment in guinea-pigs. ABR thresholds to click stimuli were recorded. DPOAE amplitude input/output functions were recorded using three different primary tone level conditions. In one condition, L1 was changed relative to a fixed L2. In the next condition, L2 was changed relative to a fixed L1. In the third condition, L1 and L2 were both changed while maintaining a consistent L1-L2 difference. Baseline L1-L2 differences were determined by adjusting L2 to produce the maximum DPOAE amplitude in each ear of each subject. Guinea-pigs were treated for a four week period with intramuscular injections of gentamicin. ABRs and DPOAEs were monitored and compared to baseline recordings or untreated control groups. DPOAE testing detected cochlear damage earlier than ABR testing. Changes in DPOAE input/output functions were noted after two weeks of treatment while changes in ABR threshold were not identified until after three weeks of treatment. The sensitivity of the DPOAE testing was related to the stimulus conditions utilized. L1-L2 differences were determined in the control group and for the initial test session by fixing L1 at 75 dB SPL and lowering L2 until the maximum DPOAE amplitude was obtained for each ear. All subsequent testing was begun using the optimal L1-L2 difference for each ear. The stimulus condition in which only L1 was changed and L2 was fixed resulted in the least sensitive DPOAE indicator of cochlear damage. The condition in which both L1 and L2 were changed, but the L1-L2 difference remained constant, resulted in the most sensitive indicator of damage. The onset and degree of cochlear damage secondary to gentamicin treatment was subject dependent. This study demonstrates that 2f1-f2 DPOAE testing is preferable to click evoked ABR testing for early detection of gentamicin toxicity of the cochlea. It also indicates that DPOAE stimulus parameters must be considered when developing test protocols. Specifically, recording the DPOAE amplitude input/output function while maintaining an effective L1-L2 difference is preferable to changing either L1 or L2 individually.

Acoustic Stimulation

Sestamibi parathyroid scanning and preoperative localization studies for patients with recurrent/persistent hyperparathyroidism or significant comorbid conditions: development of an optimal localization strategy.

For patients with previous thyroid or parathyroid surgery and for those with significant comorbid conditions, noninvasive and invasive modalities exist for the preoperative localization of pathologic parathyroid tissue. Formal localization at our institution involves obtaining two studies that are independently positive for the same location. The studies utilized have included ultrasound, CT scans, MRI, technetium-99m/thallium-201 (Tc-Tl) imaging, and more recently, (99m)Tc-sestamibi (20-25 mCi) (MIBI) scans. These were followed by arteriography and/or venous sampling if necessary. From January 1992 through October 1995, 25 patients underwent preoperative parathyroid localization (10 reoperation, 3 grave hypercalcemia, 2 concurrent goiter, 2 cerebral vascular accident, 1 bleeding disorder, and 1 malignant ventricular arrhythmia) and were evaluated prospectively during the changeover from Tc-Tl to MIBI scanning at our institution. A total of 92 studies were obtained. All 25 patients were operated on by a single surgeon, and in each case the parathyroid adenoma was successfully resected with minimal morbidity (1 permanent hypoparathyroid and 1 temporary recurrent laryngeal nerve injury). True positives interpreted preoperatively: MIBI, 14 of 19 (74%); CT scan, 13 of 19 (68%); Tc-Tl, 4 of 8 (50%), ultrasound, 9 of 20 (45%); MRI, 8 of 14 (57%); arteriography, 3 of 7 (43%); venous sampling, 3 of 4 (75%); and positron emission tomography, 0 of 1. There were no false-positive MIBI scans. These results suggest that when formal parathyroid localization is needed in reoperative/complicated patients, 1) MIBI appears to be the most sensitive and specific study, and 2) the MIBI scan should be the initial study in any situation in which preoperative localization is needed. Ultrasound can be useful for patients with significant comorbidities who have not been previously explored. CT or MRI should then be used if further evaluation is needed. If the use of these noninvasive modalities does not produce positive gland localization, selective venous sampling should be utilized as the definitive procedure.

Adenoma

Evoked and spontaneous electromyography to evaluate lumbosacral pedicle screw placement.

STUDY DESIGN: A prospective study was performed to evaluate the effectiveness of evoked and spontaneous electromyography in predicting pedicle wall breakthrough and subsequent lumbar radiculopathy occurring after placement of pedicle screw instrumentation of the lumbar spine. OBJECTIVES: To correlate cortical breakthrough of the pedicle wall with an electrically evoked electromyography threshold of stimulation, to assess the sensitivity of mechanically evoked electromyography for nerve root irritation, and to correlate postoperative nerve root irritation with intraoperative findings. SUMMARY OF BACKGROUND DATA: Pedicle wall breakthrough has been evaluated by radiographic means and found to be difficult to evaluate. Methods to perform both electrically evoked and mechanically evoked electromyography have been developed more sensitive tests for breakthrough. METHODS: Twenty-five patients receiving 112 pedicle screws were evaluated. RESULTS: Cortical breakthrough was associated with electrically evoked electromyography threshold of less than 11 milliAmps. Not all screws that had broken through the pedicle wall caused a postoperative radiculopathy. Electromyographic activity was sensitive to nerve root stimulation. CONCLUSIONS: Measuring the electrically evoked electromyography threshold of stimulation helps to assess pedicle screw placement. Mechanically evoked electromyography indicates intraoperative nerve root displacement. Postoperative radiculopathy correlated with pedicle wall breakthrough, but did not occur in every case.

Adolescent

Detection of malignancies with SPECT versus PET, with 2-[fluorine-18]fluoro-2-deoxy-D-glucose.

PURPOSE: To compare single photon emission computed tomography (SPECT) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography (PET) with FDG to evaluate malignancies. MATERIALS AND METHODS: PET and SPECT, with fluorine-18 sodium fluoride, were performed sequentially in a cylindric phantom that contained different size spheres with activity ratios of 5:1, 10:1, and 15:1. PET and SPECT were also performed in 24 patients with known or suspected malignancies. RESULTS: Sensitivities of PET and SPECT were 2,238 cpm/microCi (82.8 cpm/MBq) and 129 cpm/microCi (4.8 cpm/MBq), respectively (reconstructed spatial resolution, 7 and 17 mm, respectively [13-cm radius of rotation]). In the phantom studies, lesions of 1.5 and 1.3 cm or more in diameter were detected with a ratio of 5:1 and 10:1, respectively, and an information density of 150 counts per square centimeter. At FDG PET, 46 hypermetabolic lesions consistent with tumor were depicted in patients; at FDG SPECT, 36 (78%) were depicted. Sensitivity of FDG SPECT was 92% for detection of malignancies 1.8 cm or more in diameter seen at FDG PET. CONCLUSION: Findings at FDG SPECT can help differentiate benign from malignant lesions.

Adult

Effects of acute and chronic exercise on fat metabolism.

Fatty acids are an important source of energy for skeletal muscle contraction, particularly during exercise of mild-moderate intensity, prolonged duration, and in the fasting state. Plasma FFA transported from remote adipose tissue stores and triglycerides contained within skeletal muscle fibers are the major sources of these fatty acids. The relative contribution of each source is dependent on the mode, intensity, and duration of exercise and on training status. Plasma FFA oxidation is directly related to the rate of lipolysis in adiopose tissue. The most potent stimulants of the latter are the catecholamines, but a lower plasma insulin concentration during exercise also plays a contributory role. In contrast, intramuscular triglyceride hydrolysis appears to be mediated entirely by beta 2-adrenergic stimulation. Endurance training substantially enhances fatty acid oxidative capacity in skeletal muscle and increases the proportion of energy derived from fatty acid oxidation during exercise. In addition, the sympathoadrenal response to exercise is markedly blunted in the trained state. Studies conducted in our laboratory indicate that plasma FFA and glycerol concentrations and whole body FFA uptake and oxidation are all decreased during moderate-intensity exercise at the same absolute work rate after physical conditioning, probably because of the reduction of sympathoadrenal activity. However, the lipolytic response to catecholamines also is enhanced in trained subjects. Perhaps as a consequence, the magnitude of the decrease in lipolysis and plasma FFA oxidation is less than the decrement in sympathoadrenal activity in the same individuals during exercise in the trained state. Other investigations were conducted in our laboratory to determine the source of the additional fatty acids oxidized in physically conditioned subjects. These studies demonstrated that during moderate-intensity exercise at the same absolute work rate, depletion of triglycerides from within skeletal muscle fibers was twice as great after, as opposed to, before training. Regardless of training status, intramuscular triglyceride use accounted for about 90% of the oxidized fatty acids that were not supplied from adipose tissue via the plasma. Intramuscular triglycerides were the source of virtually all of the additional fatty acids oxidized in the trained state. Both before and after physical conditioning they explained the discrepancy between the rates of plasma FFA and total fat oxidation during moderate-intensity exercise of up to 2 hr in duration.

Adaptation, Physiological

Localizing retrocochlear hearing loss.

PURPOSE: The origin of acute/sudden hearing loss is multifactorial. The association of vestibular symptoms does not necessarily isolate the pathologic condition to the inner ear. The audiogram provides a screen for differentiating conductive from sensorineural loss but often fails to provide more localizing information. METHODS: Three unusual patients with a variety of retrocochlear presentations of hearing loss are presented. Along with conventional auditory brainstem response (ABR) testing, newer auditory tests, including otoacoustic emissions and three-dimensional ABR analysis, can facilitate site-of-lesion testing. Magnetic resonance imaging (MRI) also provides graphic documentation for sources of retrocochlear hearing loss. RESULTS: One patient had gamma-knife treatment of an arteriovenous malformation, incurring a localised lesion to the inferior colliculus contralateral to the side of hearing loss. This effectively eliminated wave V, as confirmed by three-dimensional ABR analysis. A second patient with human immunodeficiency virus developed sudden complete hearing loss with retained otoacoustic emissions, confirming a retrocochlear lesion. A third patient with acute otitis media with sudden hearing loss and vertigo had an abnormal ABR and "mass lesion" on MRI. Hearing subsequently returned to normal, as did a repeated scan. CONCLUSIONS: The unique aspects of each case of retrocochlear hearing loss and the applied auditory electrophysiologic tests are reviewed.

Adult

Short latency visual evoked potentials to flashes from light-emitting diodes.

Short latency visual evoked potentials (SVEPs) have been described in response to high-intensity, strobe flashes. High-intensity flashes can now be generated from goggle-mounted light emitting diodes (LEDs) and the SVEPs to such flashes have been shown to be reproducible across subjects, avoiding photic spread to the examination room and acoustical artifacts from the strobe stimulator. In this study, SVEPs from multichannel records are described in terms of normative latencies and amplitudes, as well as scalp distributions, to explore their generators. Potentials were recorded from 10 young male subjects, from 16 scalp locations, in response to flashes from goggle-mounted LEDs. Flashes were presented to each eye in turn, as well as binocularly. The latencies, scalp distributions and intersubject variabilities of the LED evoked SVEPs were similar to those obtained with strobe flashes. SVEP components were divided into 3 groups, according to their latency and the electrodes at which they were recorded with the largest amplitudes: periocular (under 40 msec latency), fronto-central (40-55 msec) and parieto-occipital (55-80 msec latency). The scalp distributions observed in this study suggest subcortical generators along the visual pathway, beginning at the retina. The use of goggle-mounted LEDs should promote routine evaluation of the integrity of the visual pathway between retina and cortex using SVEPs.

Adult

The origin of the human auditory brain-stem response wave II.

Auditory brain-stem responses (ABRs) were recorded from human subjects undergoing neurosurgical procedures which exposed the auditory nerve. Scalp recordings indicated that the latency of the negativity between waves I and II (In) and the latency of positive peak II (IIp) were shorter when the nerve was suspended in air than when the nerve was submerged in cerebrospinal fluid or saline, while earlier and later waves remained unaffected. These results could not be attributed to changes in stimulus or recording parameters or conduction velocity. Computational and somatosensory experimental evidence of stationary potentials generated by physical properties of the volume conductor, including changes in conductivity or geometry, are presented to develop a model of wave IIp generation. The results of this study suggest that wave IIp (and probably In) are manifestations of current flux asymmetries across conductivity boundaries created by the temporal bone-cerebrospinal fluid intradural space-brain-stem interfaces. The current flux asymmetries are generated as the propagating auditory nerve action potential crosses the conductivity boundaries. These results also indicate that the physical characteristics of the volume conductor and neural pathways must be considered when interpreting surface recorded evoked potentials.

Action Potentials