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Biomedical subjects

D McFadden

Publications and source records attributed to D McFadden.

At least 73 records · Page 4Linked to original sources
PubMed1986

Substance P-induced intestinal secretion of water and electrolytes.

This study was initiated to determine if raised (carcinoid) plasma concentrations of substance P induced jejunal secretion of water and electrolytes. Five dogs had isolated and cannulated 25 cm jejunal segments perfused at 2 ml/min with a neutral, isotonic perfusate. Saline, 1.0 ml, was infused intravenously during basal and recovery periods, while substance P was administered intravenously at 75 ng/kg/min (55 pmol/kg/min) during the four 15 minute experimental periods. Infusion increased plasma SP concentrations from basal (5.8 +/- 1.3 pg/ml) to a mean plateau level of 121.2 +/- 25.2 pg/ml (mean +/- SEM). During SP infusion, intestinal secretion of water, Na+, and Cl- were documented (H2O basal +102 +/- 60 to SP -275 +/- 60; microliter/min; Na+ basal +19.8 +/- 7.2 to SP -23.2 +/- 7.5 microEq/min; Cl- basal 21.7 +/- 7.5 to SP -16.5 +/- 5.6 microEq/min). Under basal conditions, there was minimal secretion of potassium (-0.264 +/- 0.282 microEq/min); during SP infusion, K+ flux was altered to significant secretion (-1.784 +/- 0.271 microEq/min). Serum concentrations of Na and Cl were unchanged during SP infusion, but serum potassium concentrations fell from 4.64 +/- 0.12 to 3.85 +/- 0.40 mEq/l. The data demonstrate that substance P at levels noted in the carcinoid syndrome induces significant jejunal secretion of water and electrolytes in the dog.

Animals↗
PubMed1986

Smoking inhibits asbestos clearance.

To determine whether smoking affects the clearance of asbestos fibers, guinea pigs were given amosite asbestos by intratracheal instillation and divided into 3 groups: (1) nonsmokers, (2) animals exposed to smoke only after asbestos instillation, and (3) animals exposed to smoke both before and after asbestos instillation. Asbestos fiber concentrations and sizes were measured at 1 wk and 1 month after exposure. Between 1 wk and 1 month the asbestos burden in nonsmokers decreased on average 6-fold, whereas both smoking groups failed to show a significant decrease. Over this time period, the mean length of retained fibers increased in the nonsmokers but decreased in both smoking groups. This phenomenon was seen in tissue samples and lavage samples, although lavaged fibers were consistently shorter than tissue fibers. We conclude that in this model, cigarette smoking impedes asbestos clearance, largely by increasing retention of short fibers. This increased pulmonary fiber burden may be important in the increased disease rate seen in asbestos workers who smoke.

Animals↗
PubMed1986

Cigarette smoke increases the penetration of asbestos fibers into airway walls.

For study of the penetration of asbestos fibers into airway walls, guinea pigs were given amosite asbestos by intratracheal instillation. Half of the animals were also exposed to cigarette smoke. Animals were sacrificed at 1 week and 1 month, and numbers of fibers in airway walls were counted in histologic sections. In both smoke-exposed and nonexposed groups, numbers of fibers per square millimeter of airway wall increased from 1 week to 1 month in the respiratory bronchioles. At each time period, smoke-exposed animals had significantly higher numbers of fibers in the airway walls, compared with nonexposed animals. It is concluded that 1) continued transport of fibers into interstitial tissues may be the reason that asbestosis can progress after cessation of exposure; 2) cigarette smoke increases the penetration of fibers into airway walls. This effect may play a role in the increased incidence of disease seen in smoking, compared with nonsmoking, asbestos workers.

Animals↗
PubMed1985

Secretory effects of intravenous serotonin on the proximal jejunum of the awake dog.

The intestinal secretory effects of hyperserotoninemia were studied in conscious dogs with cannulated, exteriorized chronic proximal jejunal segments. A basal absorptive state for water and electrolytes was significantly changed to a secretory state for water, sodium ion, chloride ion, and potassium ion when serotonin was infused intravenously at 30 micrograms/kg per minute. This effect disappeared with the cessation of the infusion. During infusion, whole blood serotonin concentrations were similar to those in patients with the carcinoid syndrome. Diarrhea developed in all animals studied during infusion, and significant hypokalemia also occurred. These results support a primary role for serotonin in the pathogenesis of diarrhea associated with the carcinoid syndrome.

Animals↗
PubMed1985

Verapamil inhibition of the intestinal effects of substance P.

The undecapeptide substance P (SP) is contained in enterochromaffin cells and circulates in high concentrations in patients with carcinoid syndrome. We have previously reported that elevated SP levels, simulating those reported in patients with carcinoid syndrome, induce profound changes in intestinal water and electrolyte secretion, motility, and blood flow in a canine model. The purpose of this study was to attempt to block the effects of circulating carcinoid levels of SP on intestinal secretion and motility with the calcium channel blocker verapamil. In five dogs a chronic proximal jejunal Thiry-Vella loop was constructed, and after a 2-week recovery the loops were perfused with an isotonic test solution containing 14C-polyethylene glycol as a volume marker. Motor activity was measured by changes in intraluminal pressure and a motility index was calculated with computer-assisted planimetry and expressed as square millimeters per 5 minutes. After a 30-minute baseline period, SP was infused at 50 ng/kg/min for 90 minutes. SP circulating levels rose from a baseline of 6.2 +/- 1.3 pg/ml to a peak of 93.3 +/- 3.1 pg/ml during this infusion. Thirty minutes after the start of this SP infusion, a simultaneous infusion of verapamil (5.0 micrograms/kg/min) was begun at a separate site. During SP infusion there was a significant secretory response of water (-48 +/- 12 microliters/min), Na+ (-7.7 +/- 2.5 microEq/min), Cl- (-8.8 +/- 2.7 microEq/min) and K+ (-0.57 +/- 0.14 microEq/min), and hypermotility (motility index: 1479 +/- 138 mm2/5 min). When verapamil was added a reversal of secretion to net absorption was observed (water: + 116.9 +/- 15.6 microliter/min; Na+: + 13.8 +/- 2.1 microEq/min; Cl-: + 5.5 +/- 2 microEq/min; K+: + 0.38 +/- 0.9 microEq/min) (p less than 0.05). In addition, there was a reduction in motility (motility index: 853 +/- 92 mm2/5 min; p less than 0.05). These results confirm that SP has profound effects on both intestinal motility and secretion and that calcium channel blockade reduces these effects significantly.

Animals↗
PubMed1984

Aspirin-induced hearing loss as a model of sensorineural hearing loss.

Performance in forward-masking, temporal-integration, and gap-detection tasks was measured in five normal-hearing subjects before and during a five-day period of aspirin use. The drug regimen was 3.9 g per day, taken in four equal doses at 6-h intervals. In the subjects showing substantial temporary hearing loss induced by the aspirin, (1) forward masking declined at about a normal rate as the masker-to-signal interval was increased, (2) the temporal-integration functions were flatter than normal, and (3) detection of a temporal gap was worse than normal at low sound-pressure levels (SPLs) but was essentially normal at levels above about 60 dB SPL. These aspirin-induced changes in performance are similar to the differences observed between normal listeners and listeners with mild sensorineural hearing loss. Thus, temporary, aspirin-induced hearing loss offers promise as a model condition for sensorineural hearing loss. The advantages offered by this model include all those typically attributed to within-subjects experimental designs, as well as the ability to manipulate the amount of hearing loss. Its primary disadvantages are that the hearing loss is not asymmetrically distributed toward the high-frequency region, as it typically is with sensorineural deafness, and there are large individual differences in the amount of temporary hearing loss induced by fixed doses of aspirin.

Adult↗
PubMed1984

Aspirin abolishes spontaneous oto-acoustic emissions.

Spontaneous oto-acoustic emissions (OAEs) were measured prior to, during, and following administration of aspirin. The dose schedule was three 325-mg tablets every 6 h for a total of 16 doses (3.75 days). In every subject studied, all spontaneous OAEs gradually diminished and then disappeared during the drug regimen. Emissions that were initially small disappeared within 14-20 h of beginning the drug regimen (3-4 doses), while initially large emissions took 40-70 h (7-12 doses) to disappear completely. In contrast, the initial size of an emission appeared unrelated to the time required for it to recover to full strength once drug administration ceased. The recovery process was highly idiosyncratic, with the emissions of some subjects returning to full strength within 24 h, while for other subjects, full recovery required several days. In two subjects having multiple emissions in the same ear, the relative sizes of the different emissions often changed greatly during the disappearance and recovery phases. When small frequency shifts appeared for these subjects, they appeared--and were in the same direction--for each of the multiple emissions. In a related experiment, the spontaneous emission was unchanged in one subject who took a drug that inhibits the intracellular entry of calcium ions (verapamil).

Aspirin↗
PubMed1983

Aspirin can potentiate the temporary hearing loss induced by intense sounds.

UNLABELLED: Aspirin is known to produce a reversible loss of hearing that can be as great as 40 dB, depending upon the dose and the individual subject. Here we show that aspirin-induced losses exacerbate the temporary hearing loss induced by exposure to intense sound. EXPOSUREs that ordinarily produce about 14 dB of temporary threshold shift (TTS) will produce about 18-27 dB of TTS if the listener has been taking 3.9 g of aspirin for the past two days or more. A lesser dose or a shorter duration of use produces a smaller, or no, increment in temporary hearing loss. This greater TTS, and an apparent prolongation of recovery from exposure, make chronic aspirin use ill-advised for people routinely exposed to intense sounds. EXPOSURE: 2500 Hz, 10 min, varying intensity. TTS frequency: 3550 Hz. Psychophysical method: 2IFC, adaptive.

Adult↗
PubMed1983

Intense sounds may alter the mechanical properties of the cochlear partition.

Morphological and structural changes have been observed in various cochlear elements following exposure to intense sounds. Whether these changes are sufficient to locally alter the mechanical properties of the cochlear partition is unknown. Here a psychophysical test for mechanical changes in the partition is developed and applied. Monaural exposures to an intense 1700-Hz tone were preceded and followed by a binaural task in which the subject adjusted the interaural time difference of a 250-Hz tone in order to perceive it as centered inside his head. If the local gradients of mass, stiffness, and/or coupling were altered by the exposure, then the post-exposure settings should contain a time lead toward one ear or the other, depending upon the direction of the mechanical changes. Following exposure to an intense tone, the maximum temporary threshold shift (TTS) is often displaced upward in frequency from the exposure stimulus--an effect widely known as the half-octave shift in TTS. Time leads toward the nonexposed ear in the post-exposure centering task would be in accord with a mechanical-change explanation of the half-octave shift. Settings in this direction were observed with the most intense and longest durations of exposure used, but with less intense or shorter exposures, the post-exposure settings were initially toward the exposed ear. Thus, the psychophysical evidence reported here supports the idea that exposure to intense sounds does produce temporary, local changes in cochlear mechanics, but it fails to provide a simple confirmation of the possibility that these mechanical changes underlie the half-octave shift in TTS.

Adult↗
PubMed1983

Frequency patterns of TTS for different exposure intensities.

Temporary threshold shift (TTS) was measured for several different test frequencies following exposure to a 2500-Hz tone. The intensity of the exposure tone was varied from 82 to 97 dB SPL; its duration was 5 or 10 min. In each post-exposure session, TTS was followed for four test frequencies using a method of adjustment. In all cases, the "center of balance" of the TTS pattern moved upward in frequency as exposure intensity increased. This outcome is consistent with the idea of a basalward migration of the traveling-wave envelope with increasing exposure intensity, but the evidence is not unequivocal.

Acoustic Stimulation↗
PubMed1983

Upward shifts in the masking pattern with increasing masker intensity.

Masking patterns obtained with forward-masking paradigms and relatively intense maskers sometimes have their peaks at the masker frequency and sometimes at a frequency well above it. Here it is shown that which outcome is obtained depends upon certain temporal parameters of the procedure. Specifically, the masking pattern for a 2000-Hz tone showed a gradual shift toward higher frequencies as masker intensity was increased from 65 to 95 dB SPL when long signals (about 50 ms) and long masker-to-signal intervals (about 50 ms) were used, but the effect was absent or smaller when the signals and intervals were short. This shift did not occur with a 750-Hz masker. Upward shifts in the masking pattern with increasing masker intensity are in accord with the view that the peak of displacement of the traveling-wave envelope migrates basally with increasing intensity--an idea that has frequently been suggested as an explanation of the so-called half-octave shift so routinely seen in auditory fatigue experiments.

Acoustic Stimulation↗
PubMed1978

Binaural detection at high frequencies with time-delayed waveforms.

Recent research has demonstrated that the binaural system can utilize ongoing interaural time differences for lateralization at high frequencies as well as at low frequencies. The requirement is that the signal be complex so that the time difference appears as a delay in the envelope of the waveform at one ear. Reported here are several masking experiments that examine detection performance with time-delayed signals or maskers. In the first experiment, the signal was a 50-Hz band of noise centered at 4000 Hz that was time delayed by different amounts on different blocks of trials; the masker was similar band of noise, presented diotically. Large masking-level differences (MLDs) were obtained for some values of time delay, but the MLDs did not increase monotonically within time delay as they should were envelope time delay the basis for detection performance. Subsequent experiments in which the masker was time delayed and the signal was a diotic, high-frequency tone, revealed that detectability follows the autocorrelation function, and that MLDs as large as 24 dB can be obtained at 4000 Hz at time delays corresponding to negative values in the autocorrelation function. Examination of the signal-plus masker waveforms in these conditions reveals that ongoing interaural differences in level and cycle-by-cycle time exist in those conditions that yield MLDs. Since the time differences are small by usual standards, the basis for detection performance in these conditions appears to be the ongoing interaural level differences. In a final experiment, lateralization performance was measured for a time-delayed, complex waveform in the presence of maskers of various intensities. The results show that subjects are able to extract information about the time delay in the envelope even when the signal is added to a masker of equal intensity or greater. Thus, at the small signal-to-noise ratios used in our detection experiments, extraction of envelope time information was impossible, but also unnecessary, for detection was accomplished on the basis of another cue--most likely the ongoing interaural level differences.

Auditory Perception↗