Biomedical subjects

D F Wilson

Publications and source records attributed to D F Wilson.

At least 73 records · Page 4Linked to original sources

PubMed1995

Inhibitory action of nicotinic antagonists on transmitter release at the neuromuscular junction of the rat.

The effects of two nicotinic antagonists, d-tubocurarine (TC) and hexamethonium (HEX) were tested on the rat diaphragm neuromuscular junction during train-of-six stimuli to determine if a second action of these antagonists on evoked release could be demonstrated, in addition to its known impact of blocking the autoreceptor pathway. To minimize the autoreceptor pathway, the preparations were examined under low transmitter release conditions. It was observed that both compounds significantly depressed the end-plate potential amplitudes more than the miniature end-plate potential amplitudes, while also significantly depressing quantal release output. This inhibitory action is contrary to what is observed when transmitter release is high, where feedback regulation via the autoreceptors serves a prominent role. It is concluded that this depressive action on transmitter output contributes to onset of tetanic fade and that when higher concentrations of these antagonists are used this inhibitory action of TC and HEX may override autoreceptor feedback regulation.

Animals↗

PubMed1995

Ossiculoplasty with polymaleinate ionomeric prosthesis.

With the continued concern over the possible transmission of viral infections through homologous middle ear implants, there is increasing pressure to develop a truly biocompatible alloplastic middle ear prosthesis. The polymaleinate ionomer, which has been used in dentistry as a filling and luting material for more than 15 years, has recently been used to construct total and partial ossicular replacement prostheses. In an attempt to evaluate these new implants, a multicenter prospective clinical trial was initiated. To date, 92 patients have undergone implantation. The follow-up interval ranged from 3 months to 22 months. Although it is premature to discuss the long-term results, the preliminary surgical experience and audiometric data with these implants are reviewed. From a surgical perspective, the ionomeric prostheses were easily contoured with a diamond burr and were not prone to shattering. Preliminary follow-up audiometric data were available on 80 patients (59 partial ossicular replacement prostheses and 21 total ossicular replacement prostheses). Of the 59 partial ossicular replacement prostheses the air-bone gaps (average of 500 Hz, 1 kHz, 2 kHz and 3 kHz) were as follows: 0 dB to 10 dB, 15 (25%) of 59; 11 dB to 20 dB, 20 (34%) of 59; 21 dB to 30 dB, 11 (19%) of 59; and greater than 30 dB, 13 (22%) of 59. Of the 21 total ossicular replacement prostheses the air-bone gaps were as follows: 0 dB to 10 dB, 6 (29%) of 21; 11 dB to 20 dB, 6 (29%) of 21; 21 dB to 30 dB, 5 (24%) of 21; and greater than 30 dB, 4 (19%) of 21.

Acoustic Stimulation↗

PubMed1995

Comparison of postasphyxial resuscitation with 100% and 21% oxygen on cortical oxygen pressure and striatal dopamine metabolism in newborn piglets.

The present study tests the hypothesis that ventilation with 100% O2 during recovery from asphyxia leads to greater disturbance in brain function, as measured by dopamine metabolism, than does ventilation with 21% oxygen. This hypothesis was tested using mechanically ventilated, anesthetized newborn piglets as an animal model. Cortical oxygen pressure was measured by the oxygen-dependent quenching of phosphorescence, striatal blood flow by laser Doppler, and the extra-cellular levels of dopamine and its metabolites by in vivo microdialysis. After establishment of a baseline, both the fraction of inspired oxygen (FiO2) and the ventilator rate were reduced in a stepwise fashion every 20 min over a 1-h period. For the subsequent 2-h recovery, the animals were randomized to breathing 21 or 100% oxygen. It was observed that during asphyxia cortical oxygen pressure decreased from 36 to 7 torr, extracellular dopamine increased 8,300%, and dihydroxyphenylacetic acid and homovanillic acid decreased by 65 and 60%, respectively, compared with controls. During reoxygenation after asphyxia, cortical oxygen pressure was significantly higher in the piglets ventilated with 100% oxygen than in those ventilated with 21% oxygen (19 vs. 11 torr). During the first hour of reoxygenation, extracellular dopamine levels decreased to approximately 200% of control in the 21% oxygen group, whereas these levels were still much higher in the 100% oxygen group (approximately 500% of control). After approximately 2 h of reoxygenation, there was a secondary increase in extracellular dopamine to approximately 750 and approximately 3,000% of baseline for the animals ventilated with 21 and 100%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Relationships of dopamine, cortical oxygen pressure, and hydroxyl radicals in brain of newborn piglets during hypoxia and posthypoxic recovery.

The present study describes the relationships of extracellular striatal dopamine, cortical oxygen pressure, and striatal hydroxyl radicals in brain of newborn piglets during hypoxia and posthypoxic reoxygenation. Hypoxia was induced by reducing the fraction of inspired oxygen (FiO2) from 22% (control) to 7% for 1 h. The FiO2 was then returned to the control value and measurements were continued for 2 h. Cerebral oxygen pressure was measured by the oxygen dependent quenching of phosphorescence and extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and hydroxy radicals in the striatum were determined by in vivo microdialysis. Hypoxia decreased the cortical oxygen pressure from 47 +/- 2 to 9 +/- 1.3 torr (p < 0.001); the levels of extracellular dopamine in the striatum increased to 16,000 +/- 3,270% of control (p < 0.01), whereas the levels of DOPAC and HVA decreased to 25.3 +/- 6% (p < 0.001) and 36 +/- 5% (p < 0.01) of control, respectively. Compared with control, the hydroxyl radical levels at each time point were not significantly increased during hypoxia, although the sum of the measured values was significantly increased (p < 0.05). During the first 5 min after FiO2 was returned to 22%, the cortical oxygen pressure increased to control values and stayed at this level for the remainder of the measurement period. The extracellular level of dopamine declined to values not statistically different from control during 40 min of reoxygenation. During the first 10 min of reoxygenation, DOPAC and HVA further decreased and then began to slowly increase. By 70 min of reoxygenation, the values were not significantly different from control.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

Comparison of the efficacy of blood and polyethylene glycol-hemoglobin in recovery of newborn piglets from hemorrhagic hypotension: effect on blood pressure, cortical oxygen, and extracellular dopamine in the brain.

BACKGROUND: Successful blood substitutes, when infused in place of an equal volume of whole blood, provide similar delivery of oxygen to the tissues without introducing abnormalities in cellular metabolism. STUDY DESIGN AND METHODS: Equal volumes of whole blood (control), polyethylene glycol-hemoglobin solution at 6 g per dL, dextran solution, and physiologic saline were compared for their ability to reverse the effects of hemorrhagic hypotension on oxygenation and dopamine metabolism in the brain of newborn piglets. The decrease in mean arterial blood pressure was used as a measure of the hemorrhagic insult. Cerebral oxygen pressure was determined optically by the oxygen-dependent quenching of phosphorescence, and the extracellular level of dopamine in the corpus striatum was determined by in vivo microdialysis. RESULTS: Following a 2-hour stabilization after implantation of the microdialysis probe in the corpus striatum, the mean arterial blood pressure was decreased from 88 +/- 7 torr (control) to 42 +/- 5 torr by the removal of blood in a stepwise manner, over a period of 60 minutes. Decrease in mean arterial blood pressure caused a progressive stepwise decrease in cortical oxygen pressure from 48 +/- 5 torr to 16 +/- 4 torr at the end of bleeding. As a consequence of the decrease in oxygen pressure, extracellular dopamine increased progressively to about 2300 percent of the control value. When a volume of blood equal to that removed was returned and bicarbonate was injected to help correct arterial pH, blood pressure, cortical oxygen pressure, and extracellular dopamine all returned within the 20- to 30-minute recovery period to values not significantly different from control values. An equal volume of polyethylene glycol-hemoglobin solution, even with significantly lower hemoglobin content than whole blood, gave results comparable to those with whole blood. CONCLUSION: Polyethylene glycol-hemoglobin solution, like whole blood but in contrast to physiologic saline or dextran solution, was capable of returning the mean arterial blood pressure, cortical oxygen pressures, and extracellular dopamine nearly to control levels after acute blood loss in newborn piglets.

Animals↗

PubMed1995

Proteoglycan changes in carcinogen (4NQO)-treated rat tongue mucosa.

The purpose of this study was to undertake preliminary analyses of the extracellular proteoglycans in carcinogen [4-nitroquinoline N-oxide (4NQO)]-treated rat tongue mucosa. Experimental rats were exposed to twice-weekly applications of 4NQO in propylene glycol for six months, after which the animals were killed. Control and 4NQO-treated tissues were subjected to sequential aqueous extractions of proteoglycans under associative and dissociative conditions, followed by alkaline cleavage of protein-glycosaminoglycan linkages to yield a glycosaminoglycan residue. Tissues subjected to 4NQO applications contained smaller proportions of proteoglycans which were readily soluble under associative and dissociative conditions. Proportionately more proteoglycan remained strongly associated with other intercellular tissue components, being released only by alkaline cleavage. These biochemical alterations in preinvasive 4NQO-treated epithelium and connective tissues, together with an observed associated change in water retention by the connective tissue, occurred prior to actual neoplastic invasion and suggest differences in macromolecular conformation and orderliness. We hypothesize that these changes are related to the phenomenon of neoplastic epithelial invasion.

4-Nitroquinoline-1-oxide↗

PubMed1995

Diaphragm microvascular plasma PO2 measured in vivo.

Phosphorescence quenching techniques measure microvascular PO2 without direct surgical manipulation of the tissue. At a given arterial PO2, microvascular PO2 reflects the local O2 uptake-to-O2 delivery ratio, i.e., VO2/QO2. We evaluated the potential of phosphorescence quenching to determine microvascular PO2 in the rat costal diaphragm (PdiaO2). PdiaO2 and arterial blood gases were monitored across transient changes of inspired O2 among 21, 10, and 100% and also during hypotensive states evoked by progressive phlebotomy. After a transit delay, PdiaO2 responded rapidly to alterations of inspired and thus arterial PO2, with half times of the response averaging 5-7 s for switches to a lower inspired O2 (i.e., from 21 to 10%, from 100 to 21%, and from 100 to 10%) and also from 10 to 21%. By comparison, half times of the 10 to 100% and 21 to 100% switches were longer [11 s (P = 0.085) and 21 s (P < 0.05), respectively]. Below a mean arterial blood pressure (BP) of 120-130 mmHg, PdiaO2 decreased as a linear function of BP, with these variables being significantly correlated in each instance (n = 5, r = 0.851-0.937, P < 0.01 for all animals). From these results, it appears feasible to measure PdiaO2 in the spontaneously breathing rat in vivo under steady-state and transient conditions. Also, during progressive hypotension, the fall in PdiaO2 is significantly related to falling BP, likely as a consequence of an increased metabolic demand (increased ventilation and diaphragm VO2) concomitant with decreased blood flow. We conclude that phosphorescence quenching techniques offer a powerful tool for assessing diaphragm physiology and pathophysiology.

Animals↗

PubMed1995

Energy metabolism in muscle approaching maximal rates of oxygen utilization.

Muscle is capable of operating over a wide range of metabolic rates. Most of the metabolic energy for work (ATP), and essentially all of the oxygen consumption of muscle, is due to mitochondrial oxidative phosphorylation. The rate of mitochondrial oxidative phosphorylation is determined by the rate of ATP consumption by the cells (demand) while the metabolic energy level at each metabolic rate is determined by the supply of oxidizable substrate and oxygen (supply). The maximal rate of metabolism is limited by several factors, including the supply of oxidizable substrates (mitochondrial dehydrogenases), of oxygen (blood supply and oxygen diffusion) and the respiratory enzyme capacity (tissue content of mitochondria).

Adenosine Triphosphate↗

PubMed1994

Effect of hemorrhagic hypotension on extracellular level of dopamine, cortical oxygen pressure and blood flow in brain of newborn piglets.

The present study describes the relationships between extracellular striatal dopamine, cortical oxygen pressure and blood flow in brain of newborn piglets during hemorrhagic hypotension. Cerebral oxygen pressure was measured optically by the oxygen dependent quenching of phosphorescence; extracellular dopamine by in vivo microdialysis; striatal blood flow was monitored by a laser Doppler. Following a 2 h stabilization period after implanting the microdialysis and laser Doppler probes in the striatum, the mean arterial blood pressure (MABP) was decreased in stepwise manner from 87 +/- 4 Torr (control) to 35 +/- 5 Torr, during 63 min. The whole blood was then reinfused and measurements were continued for 45 min. Statistically significant decrease in blood flow, 10%, was observed when arterial blood pressure decreased to about 53 Torr. With further decrease blood pressure to 35 Torr, blood flow decreased to about 35% of control (P < 0.01). Cortical oxygen pressure decreased almost proportional to decrease in blood pressure. The progressive decrease in MABP from 87 +/- 4 Torr to 65 +/- 6, 52 +/- 7, and 35 +/- 5 Torr resulted in cortical oxygen pressure decreasing from 45 +/- 4 Torr to 33 +/- 3 Torr (P < 0.05), 24 +/- 4 Torr (P < 0.01) and 13 +/- 3 Torr (P < 0.01). The levels of extracellular dopamine in the striatum increased with decreasing cortical oxygen pressure. As cortical oxygen decreased, the extracellular dopamine increased to 230%, 420% and 3200% of control, respectively. Our results show that in mild hypotension total blood flow is well maintained but oxygen pressure in the microvasculature decreases, possibly due to heterogeneity in the regulatory mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

The primary oxygen sensor of the cat carotid body is cytochrome a3 of the mitochondrial respiratory chain.

Carbon monoxide was shown to be competitive with O2 in oxygen sensing by perfused carotid bodies isolated from cats, afferent electrical activity increasing with either decreasing O2 or increasing CO. The CO-induced increase in afferent activity was fully reversed by bright light. At submaximal light intensities the extent of reversal, after correcting to equal light intensity of light quanta at each wavelength, was maximal for light of 432 +/- 2 and 590 +/- 2 nm, with a ratio (432/590) of approximately 6. This spectrum is characteristic of the CO compound of mitochondrial cytochrome a3. The photo-reversible inhibition of oxygen sensing activity by CO accounts for at least 80% of the oxygen chemosensory activity of the carotid body.

Animals↗

PubMed1994

Effect of hypoxia and reoxygenation on the activity of transglutaminase in brain of newborn piglets.

The transglutaminase activity in five regions of the brain of newborn piglets was measured and the effects of hypoxia and posthypoxic period on this activity evaluated. Enzyme activity was measured in homogenates from cortex, hippocampus, striatum, thalamus and midbrain. The control activities were 7.2, 6.2, 6.0, 5.7 and 4.6 pmol/mg protein/min, respectively. The activities at the end of an 18 min period of hypoxia induced by an FiO2 of 9% were not significantly different from control activities. By 3 h after the hypoxic episode, however, the transglutaminase activities were significantly above control levels in all five regions of the brain. Measurements of the kinetic constants of tranglutaminase indicated that increases in enzyme activity were associated with an increase in Vmax with no significant change in the apparent affinity of the enzyme for the substrate, putrescine. The increased activity of transglutaminase during the posthypoxic period, with no changes immediately after hypoxia, suggest that the increases could be due to increased enzyme synthesis rather than activation of existing enzyme. The rise in transglutaminase activity subsequent to a hypoxic episode may contribute significantly to the long-term disturbances in cellular metabolism in the immature brain induced by hypoxic episodes.

Animals↗

PubMed1994

Magnetic resonance imaging-enhancing lesions of the labyrinth and facial nerve. Clinical correlation.

OBJECTIVE: Gadolinium-enhanced magnetic resonance imaging (MRI) is useful in assessing inflammatory and neoplastic lesions of the labyrinth and facial nerve. The following cases demonstrate the ability of MRI to differentiate neoplastic from inflammatory lesions within the labyrinth. PATIENTS OR OTHER PARTICIPANTS: Nine patients were selected with enhancing lesions of the labyrinth and the facial nerve identified on MRI. INTERVENTION: Acyclovir and prednisone were prescribed for herpes zoster oticus; surgical removal of neoplastic lesions was performed. MAIN OUTCOME MEASURE: The hypothesis was developed in the course of clinical practice. No planned outcome was emphasized, as this article is based on the differential diagnoses of the cases reported. RESULTS: Gadolinium-enhanced MRI is useful in differentiating neoplastic from inflammatory lesions within the labyrinth. Axial and coronal 3-mm sections with gadolinium enhancement were necessary for identifying these lesions and particularly for recognizing the sharp enhancement of the neoplastic margin in contrast to the dull cloudy margins of an inflammatory lesion. CONCLUSIONS: The MRI differentiation of these lesions is helpful in providing appropriate medical and surgical management of neoplastic and inflammatory lesions of the labyrinth.

Adult↗

PubMed1994