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Biomedical subjects

J R Wilson

Publications and source records attributed to J R Wilson.

At least 145 records · Page 8Linked to original sources

Skeletal muscle beta-receptors and isoproterenol-stimulated vasodilation in canine heart failure.

To investigate whether heart failure alters beta-adrenergic receptors on skeletal muscle and its associated vasculature, the density of beta-adrenergic receptors, isoproterenol-stimulated adenylate cyclase activity, and coupling of the guanine nucleotide-binding regulatory protein were compared in 18 control dogs and 16 dogs with heart failure induced by 5-8 wk of ventricular pacing at 260 beats/min. Hindlimb vascular responses to isoproterenol were compared in eight controls and eight of the dogs with heart failure. In dogs with heart failure, the density of beta-receptors on skeletal muscle was reduced in both gastrocnemius (control: 50 +/- 5; heart failure: 33 +/- 8 fmol/mg of protein) and semitendinosus muscle (control: 43 +/- 9; heart failure: 27 +/- 9 fmol/mg of protein, both P less than 0.05). Receptor coupling to the ternary complex, as determined by isoproterenol competition curves with and without guanosine 5'-triphosphate (GTP), was unchanged. Isoproterenol-stimulated adenylate cyclase activity was significantly decreased in semitendinosus muscle (control: 52.4 +/- 4.6; heart failure: 36.5 +/- 9.5 pmol.mg-1.min-1; P less than 0.05) and tended to be decreased in gastrocnemius muscle (control: 40.1 +/- 8.5; heart failure: 33.5 +/- 4.5 pmol.mg-1.min-1; P = NS). Isoproterenol-induced hindlimb vasodilation was not significantly different in controls and in dogs with heart failure. These findings suggest that heart failure causes downregulation of skeletal muscle beta-adrenergic receptors, probably due to receptor exposure to elevated catecholamine levels, but does not reduce beta-receptor-mediated vasodilation in muscle.

Adenylyl Cyclases↗

Sympathetic vasoconstriction during exercise in ambulatory patients with left ventricular failure.

In patients with heart failure, exercise is thought to increase sympathetic vasoconstrictor tone. To investigate the extent of this sympathetic activation, we studied the effect of maximal exercise on nonexercising vascular beds in 35 patients with left ventricular failure (ejection fraction, 21 +/- 8%; peak exercise oxygen uptake (VO2), 12.3 +/- 3.5 ml/min/kg). In 28 patients, cardiac output and leg blood flow were measured during maximal upright bicycle exercise. Total flow to nonexercising tissue was then calculated as cardiac output--(2 x leg flow). In seven patients and six normal subjects, forearm blood flow was measured during supine bicycle exercise before and after alpha-adrenergic blockade with intravenous phentolamine. Maximal upright exercise increased the vascular resistance of nonexercising tissue from 34 +/- 16 units at upright rest to 45 +/- 25 units (p less than 0.02) but did not affect total flow to nonexercising tissue (rest, 2.9 +/- 1.0; maximal exercise, 2.8 +/- 1.4 l/min; p = NS). Supine exercise had no significant effect on forearm blood flow or vascular resistance in the normal subjects. In the patients with heart failure, supine exercise increased forearm vascular resistance from 45 +/- 17 to 58 +/- 25 mm Hg/ml/min/100 ml (p less than 0.02), again with no change in tissue flow (rest, 2.4 +/- 0.1; maximal exercise, 2.4 +/- 0.9 ml/min/100 ml; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output↗

Contribution of intrinsic skeletal muscle changes to 31P NMR skeletal muscle metabolic abnormalities in patients with chronic heart failure.

Patients with heart failure frequently exhibit abnormal skeletal muscle metabolic responses to exercise, as assessed with 31P NMR. To investigate whether these metabolic abnormalities are due to intrinsic skeletal muscle changes, we performed gastrocnemius muscle biopsies on 22 patients with heart failure (peak VO2, 15.4 +/- 4.7 ml/kg/min; ejection fraction, 20 +/- 7%) and on eight normal subjects. Biopsies were analyzed for fiber type and area, capillarity, citrate synthase, phosphofructokinase, lactate dehydrogenase, and beta-hydroxyacyl CoA dehydrogenase activity. All patients with heart failure also underwent 31P NMR studies of their calf muscle during plantarflexion at three workloads. Muscle pH responses and the relation of the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) to systemic VO2 were then evaluated. Compared with normal subjects, patients with heart failure exhibited a shift in fiber distribution with increased percentage of the fast twitch, glycolytic, easily fatigable type IIb fibers (normal subjects, 22.7 +/- 10.1; heart failure, 33.1 +/- 11.1%; p less than 0.05), atrophy of type IIa (normal subjects, 5,477 +/- 1,109; heart failure, 4,239 +/- 1,247 microns 2; p less than 0.05) and type IIb fibers (normal subjects, 5,957 +/- 1,388; heart failure, 4,144 +/- 945 microns 2; p less than 0.01), and decreased activity of beta-hydroxyacyl CoA dehydrogenase (normal subjects, 5.17 +/- 1.44; heart failure, 3.67 +/- 1.68 mol/kg protein/hr; p less than 0.05). No significant linear correlation could be identified between the slope of the Pi/PCr to VO2 relation and muscle histochemistry or enzyme activities. Similarly, no linear relation was found between intracellular pH at peak exercise and any muscle variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

Noninvasive detection of skeletal muscle underperfusion with near-infrared spectroscopy in patients with heart failure.

The present study was undertaken to determine whether near-infrared spectroscopy can be used to noninvasively assess skeletal muscle oxygenation in patients with heart failure. The difference between light absorption at 760 and 800 nm was used to assess hemoglobin-myoglobin oxygenation. Initial studies conducted in isolated canine gracilis muscle demonstrated that 760-800-nm absorption correlated closely (r = -0.97 +/- 0.01) with venous hemoglobin O2 saturation when the muscle was stimulated to contract at 0.25-5.0 Hz. In normal subjects (n = 6) and patients with heart failure (n = 8), 760-800-nm absorption changes from the vastus lateralis muscle were monitored at rest, during progressive maximal bicycle exercise, and during thigh cuff inflation to suprasystolic pressure, an intervention designed to assess minimal hemoglobin-myoglobin oxygenation. Absorption changes were expressed relative to the full physiologic range noted from rest to thigh cuff inflation. During exercise, normal subjects exhibited an initial increase in hemoglobin-myoglobin oxygenation followed by a progressive decrease in oxygenation to 27 +/- 13% of the physiologic range at the peak exercise workload of 140 +/- 9 W. In contrast, patients exhibited an initial decrease in hemoglobin-myoglobin oxygenation with the first workload, followed by a progressive further decrease to 26 +/- 13% of the physiologic range at a peak exercise workload of 60 +/- 8 W, less than half the peak workload noted in the normal subjects. At all exercise loads, hemoglobin-myoglobin oxygenation was significantly less in the patients than in the normal subjects. These data suggest that near-infrared spectroscopy can detect impaired skeletal muscle O2 delivery in patients with heart failure. This technique could provide a valuable method of assessing muscle O2 delivery in patients, particularly before and after therapeutic interventions.

Animals↗

Long-term repeatability of human alcohol metabolism, sensitivity and acute tolerance.

Thirty-eight subjects in the Colorado Alcohol Research on Twins and Adoptees (CARTA) were brought back between 3 and 39 months after their initial testing to be retested on a shortened version of the standard CARTA procedures. As before, subjects were given a dose of ethanol (0.8 g/kg) calculated to bring their blood alcohol level (BAL) to near 100 mg/dl, but no topping doses were administered in the retests to maintain BALs near peak for 3 hours, as was done previously. Repeatability (test-retest correlation) for alcohol clearance rate was near zero, repeatability for time to peak BAL was 0.36 and that for peak BAL was 0.50. Repeatabilities of prealcohol baseline scores were generally high (median 0.55) for the shortened battery of physiological, motor coordination, perceptual speed and reaction time measures. Repeatabilities were near zero for sensitivity scores (median 0.02) and were low for acute tolerance scores (median 0.10) and perceived intoxication (median 0.27). These findings are highly consistent with an earlier report on repeatabilities of responses to alcohol over a 1-month time interval.

Adoption↗

Synaptic organization of individual neurons in the macaque lateral geniculate nucleus.

Parvocellular and magnocellular neurons in the dorsal lateral geniculate nucleus of macaque monkeys were recorded electrophysiologically and then injected with HRP. The injected neurons were examined with the electron microscope. Synaptic terminals contacting the dendrites of individual neurons were classified and the synapses counted to estimate the number and distribution of each type over the entire dendritic tree. Seven parvocellular and 2 magnocellular neurons were analyzed. Two of the parvocellular neurons had presynaptic dendrites and no axons. These interneurons had electro-physiological characteristics much like those of relay neurons with the exception that their receptive field center responses had the opposite sign; i.e., they had OFF centers, while most neurons around them had ON centers. All of the relay neurons had similar types and distributions of terminal contacts. However, the distribution of each synaptic type along the dendrites of an individual neuron was not homogeneous. Retinal and F terminals were located predominantly on proximal dendrites whereas RSD terminals, either from the cortex and/or brain stem, predominated on the intermediate and distal dendrites. Parvocellular neurons were estimated to have about 500 total synapses on their dendritic trees, while magnocellular neurons had about 3000 total synapses on their dendritic trees. The retinal terminals making synaptic contacts with magnocellular neurons were also presynaptic to terminals containing flattened vesicles; these latter terminals also had synapses onto the magnocellular neuron's dendrites. Such a synaptic arrangement is called a triadic arrangement, or triad. Parvocellular neurons rarely had such triadic arrangements. In comparing these data with those of the cat, it was concluded that the major synaptic difference between relay cell types in both species (Class 1/Class 2 cells for the cat and parvo/magno cells for the monkey) was the frequent occurrence of triads for Class 2 cells and magnocellular cells versus the infrequent occurrence of triads for Class 1 cells and parvocellular cells. Although these triadic arrangements have been studied for over 2 decades, their function has yet to be determined, but probably relates to inhibition of retina signals at dendrites of magnocellular neurons in the monkey and Class 2 cells in the cat.

Animals↗

Development of acuity in a primate model of human infantile unilateral aphakia.

We are studying infant rhesus monkeys that have been reared under various conditions of deprivation to model infantile unilateral aphakia. Grating acuity was assessed in these monkeys from birth to approximately 1 year of age using the quick acuity card procedure. We found that an uncorrected aphakic eye develops little or no pattern vision. Undercorrection or near point optical correction of an aphakic eye with an extended-wear contact lens coupled with continuous occlusion of the opposite eye sometimes results in normal development of acuity in the aphakic eye but does so only at the cost of loss of vision in the occluded eye. Fifty percent partial occlusion coupled with near-point correction of the aphakic eye results in similar development of acuity for both eyes during the time tested. Monkeys wearing near-point correction in the aphakic eye and without any occlusion of the other eye show surprisingly good residual acuities in their aphakic eyes. Based on these results we conclude that aphakic eyes should be treated by providing them with an optical correction, and that occlusion of the opposite eye should be used cautiously.

Animals↗

Detection of abnormal calf muscle metabolism in patients with heart failure using phosphorus-31 nuclear magnetic resonance.

Patients with heart failure frequently report leg fatigue during exercise. At present, however, there is no objective method of detecting leg muscle abnormalities in such patients. To determine if phosphorus-31 nuclear magnetic resonance spectroscopy can provide such information, this technique was used to compare calf responses to stair climbing and plantarflexion in 20 patients with heart failure (peak oxygen consumption (VO2) of 13.6 +/- 5 ml/kg/min, ejection fraction 20 +/- 5%) and 9 age-matched normal subjects. Work was quantified by measuring VO2. At rest, both groups exhibited similar inorganic phosphorus to phosphocreatine (Pi/PCr) ratios (patients with heart failure 0.21 +/- 0.07, normal subjects 0.21 +/- 0.06, difference not significant) and pH levels (patients with heart failure 7.06 +/- 0.17, normal subjects 7.05 +/- 0.11, difference not significant). In both normal subjects and patients with heart failure, exercise resulted in a progressive rise in Pi/PCr as VO2 increased. However, examination of the relation of VO2 versus Pi/PCr revealed steeper slopes in patients with heart failure during both stair climbing and plantar-flexion. Neither form of exercise decreased calf pH in normal subjects. In the patients with heart failure, significant decreases in pH were noted during the highest work level of plantarflexion (pH of heart failure patients 6.86 +/- 0.20, pH of normal subjects 7.07 +/- 0.14, p less than 0.01). Metabolic recovery time was also prolonged in the patients with heart failure versus normal subjects (3.3 +/- 0.8 vs 2.1 +/- 0.5 minutes, respectively, p less than 0.002). These findings indicate that phosphorus-31 nuclear magnetic resonance provides objective evidence of leg muscle abnormalities in patients with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Signal-to-noise comparisons for X and Y cells in the retina and lateral geniculate nucleus of the cat.

The spike trains of X and Y retinal ganglion cell axons and neurons in the lateral geniculate nucleus (LGN) of cats were compared to determine if the visual signal could be better discriminated from the maintained activity in the LGN relative to the retina. Curves for relative or receiver operating characteristics (ROC) were derived from the interspike interval data of the spike trains using maintained activity as "noise" and visually-driven activity as the "signal". Analyses were also made using spike densities and more restricted time intervals. Although it was expected that neurons in the LGN might better distinguish the signal from the noise, the results of the ROC curve and spike density analyses did not bear out this expectation; that is, neither the X or Y cells in the LGN provided better discrimination of the visually-driven activities from the maintained activities compared to the incoming retinal information. Thus, at least in the anesthetized preparation, the LGN does not play a role in increasing the signal-to-noise ratio.

Action Potentials↗

Future directions and research issues for ergonomics and advanced manufacturing technology (AMT).

In recent years, great progress has been made in the development of computer-based technologies that support the manufacturing industries. Those concerned with advanced manufacturing technology (AMT) are becoming increasingly aware of the fundamental importance of human organisational issues for the successful development, implementation, operation and maintenance of AMT. The discipline of industrial ergonomics and occupational occupational psychology, therefore, have a significant contribution to make in this field. This paper introduces the special issue, Ergonomics Matters in AMT, and presents a discussion of some of the future directions of AMT and the likely implications for ergonomics research.

Journal Article↗

Effect on peripheral arterioles of chronic fluid and sodium retention in heart failure.

To determine whether chronic fluid and sodium retention in heart failure adversely affects peripheral arteriolar behavior, systemic vascular resistance and skeletal muscle vasodilation were compared in eight control dogs and nine dogs with chronic fluid and sodium retention (ascites = 2.3 +/- 2.3 liters) induced by rapid ventricular pacing for 2 months. At rest, both groups exhibited comparable systemic vascular resistance (control 45 +/- 14 versus heart failure 40 +/- 7 U) and femoral bed vascular resistance (control 18.7 +/- 6.9 versus heart failure 19.0 +/- 7.2 x 10(2) U) (both p = NS). Femoral bed resistance also decreased similarly in both groups during treadmill exercise (resistance at peak exercise: control 4.7 +/- 3.0 versus heart failure 4.9 +/- 0.9 x 10(2) U [p = NS]). In isolated gracilis muscle, vascular resistance was also comparable in both groups at rest (control 7.3 +/- 3.3 versus heart failure 10.2 +/- 3.6 x 10(3) U/100 g), at peak exercise (control 1.6 +/- 0.5 versus heart failure 1.8 +/- 0.9 x 10(3) U/100 g) and after maximal vasodilation with papaverine (control 0.7 +/- 0.3 versus heart failure 0.9 +/- 0.3 x 10(3) U/100 g) (all p = NS). These data suggest that chronic fluid and sodium retention in heart failure does not alter peripheral arteriolar behavior.

Animals↗

Effect of dichloroacetate on the exercise performance of patients with heart failure.

The reduced maximal exercise capacity of patients with heart failure has been attributed to skeletal muscle underperfusion with resultant intramuscular lactic acidosis and muscular fatigue. To investigate this hypothesis, the effect of dichloroacetate, a drug that decreases lactate formation by increasing pyruvate oxidation, on the maximal exercise performance of 18 patients with heart failure and reduced ejection fraction (25 +/- 9%) was examined. Exercise tests after parenteral dextrose (control) and dichloroacetate were performed 1 week apart. The sequence of interventions was randomized in a double-blind manner. Dichloroacetate decreased blood lactate at rest (control 8.0 +/- 2.5 versus dichloroacetate 5.6 +/- 2.9 mg/dl), throughout exercise and at peak exercise (control 26.0 +/- 14.3 versus dichloroacetate 19.4 +/- 10.8) (all p less than 0.05). In contrast, dichloroacetate had no effect on exercise time (control 15.2 +/- 6.0 versus dichloroacetate 15.9 +/- 6.2 min) or peak exercise oxygen consumption (control 1,280 +/- 498 ml/min versus dichloroacetate 1,312 +/- 530 ml/min) (both p = NS). In six subjects, dichloroacetate also had no effect at peak exercise on leg blood flow (control 2.8 +/- 1.1 versus dichloroacetate 3.0 +/- 0.6 liters/min) or femoral oxygen vein saturation (control 12.7 +/- 4.1% versus dichloroacetate 12.5 +/- 5.7%). These data suggest that intramuscular lactate accumulation is not responsible for muscular fatigue during exercise in patients with heart failure.

Acetates↗

Serotonergic axons in the monkey's lateral geniculate nucleus.

Axons containing serotonin (5-hydroxytryptamine, 5-HT) in the lateral geniculate nucleus of Macaca monkeys were stained using light or electron microscopic (EM) immunocytochemical labeling techniques. 5-HT labeled axons were sparsely and homogeneously distributed throughout the entire nucleus. Small varicosities were located irregularly along each axon giving them a beaded appearance. Examination of these axons at the EM level revealed that the varicosities contained synaptic vesicles that were variable in size and shape. Nearly all of the varicosities lacked synaptic contacts; only two out of over two hundred labeled varicosities appeared to form a synaptic contact, and serial sections through ten varicosities showed no discernible pre- or postsynaptic membrane specializations. 5-HT labeled axon varicosities were not observed to be preferentially located in proximity to any specific neuronal structures at either the light or EM level. 5-HT varicosities were estimated to form about 1% of the profiles containing synaptic vesicles in the neuropil of the lateral geniculate nucleus. We conclude that axons containing serotonin in the lateral geniculate nucleus release this neurotransmitter to act in a neuromodulatory manner throughout the neuropil, probably to set a general level of neuronal excitability.

Animals↗

Effect of the trichothecene deoxynivalenol on brain biogenic monoamines concentrations in rats and chickens.

Male Sprague-Dawley rats (180 g) and 28-day-old Single Comb White Leghorn Cockerels (300 g) were orally dosed with deoxynivalenol (DON) at 2.5 mg kg-1 body weight. In the first experiment, whole brains were collected at 2, 6, 12, 24 and 48 hours after the toxin treatment and analyzed for brain biogenic monoamines by high-performance liquid chromatography with electrochemical detection. Although several interesting trends were observed, DON did not influence whole brain concentrations of monoamine neurotransmitters or their metabolites in either species, at any time. In a second experiment, brains were collected 24 hours postdosing, dissected into 5 brain regions (pons and medulla oblongata, cerebellum, hypothalamus, hippocampus and cerebral cortex), and analyzed. DON treatment resulted in significantly elevated concentrations of serotonin (HT) and 5-hydroxyindole-3-acetic acid (HIAA) in all brain regions of the rat. However, this was not seen in poultry, where DON treatment resulted in a decrease in norepinephrine (NE) in the hypothalamus and hippocampus, and a decrease in dopamine (DA) in the pons and medulla oblongata region. These results suggest that DON influences brain biogenic amine metabolism, and that there may be intraspecies differences in the central effects of this mycotoxin.

Animals↗

Two-hole plate fixation for traumatic symphysis pubis diastasis.

Techniques for managing traumatic diastasis of the pubic symphysis include bed rest, hip spica casting, pelvic slings, external fixation, and internal fixation. We report herein our experience with 14 consecutively managed patients in whom we successfully stabilized traumatic pubic diastasis with a single two-hole plate fixation. The average age of the 13 men and one woman was 30 years; followup averaged 17 months. Most of the patients had associated injuries (Injury Severity Score average, 19). Nine patients had concomitant disruption of the sacroiliac joint requiring either delayed open reduction and internal fixation or prolonged skeletal traction; among the five remaining patients, time to mobilization (bed to chair) averaged 1 day. There were no complications attributable to the procedure; i.e., no infections, and no failures of fixation. In this small series of patients early two-hole plate fixation of the traumatic diastasis of the pubis satisfactorily restored the disrupted anterior pelvic ring, contributed to early mobilization of the patients, and made reduction of a concomitantly disrupted sacroiliac joint easier, whether accomplished by skeletal traction or open reduction and internal fixation during a second procedure.

Adolescent↗