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Biomedical subjects

J R Wilson

Publications and source records attributed to J R Wilson.

At least 19 recordsLinked to original sources
PubMed1995

Dissociation between exertional symptoms and circulatory function in patients with heart failure.

BACKGROUND: Patients with heart failure frequently report exertional dyspnea and fatigue. These symptoms are usually attributed to circulatory dysfunction and therefore are typically treated with cardiovascular medications. Serial assessment of exertional symptoms has also become the principal method used to assess drug efficacy in heart failure. Nevertheless, the relation between exertional symptoms in heart failure and circulatory dysfunction remains uncertain. METHODS AND RESULTS: This study was undertaken to investigate the relation between exertional symptoms, ventilatory and skeletal muscle dysfunction, and circulatory function in patients with heart failure. To this end, 52 ambulatory patients with heart failure underwent hemodynamic monitoring during maximal treadmill exercise testing. During exercise, the severity of dyspnea and fatigue was evaluated on a scale of 6 to 20 (Borg scale). The level of perceived exercise intolerance during daily activities was evaluated with the Minnesota Living With Heart Failure Questionnaire and the Yale Dyspnea-Fatigue Index. Maximal treadmill exercise increased the VO2 to 13.4 +/- 2.8 mL.min-1.kg-1, the dyspnea score to 15.7 +/- 2.3, the fatigue score to 14.8 +/- 3.4, the pulmonary wedge pressure to 28 +/- 11 mm Hg, and the pulmonary artery lactate concentration to 34.5 +/- 16.3 mg/dL and decreased the pulmonary artery hemoglobin oxygen saturation to 30 +/- 9%. The level of perceived dyspnea had no relation to the pulmonary wedge pressure and correlated only minimally with the level of excessive ventilation (r = 39). The level of perceived fatigue correlated only weakly with blood lactate concentration (r = .55). Eleven patients (21%) exhibited a normal cardiac output and wedge pressure < 20 mm Hg during exercise, 22 (42%) exhibited a normal cardiac output but wedge pressure > 20 mm Hg during exercise, and 19 (37%) exhibited reduced cardiac output and wedge pressure > 20 mm Hg during exercise. Despite these markedly different hemodynamic responses, all three groups exhibited similar levels of fatigue and dyspnea at comparable workloads and had comparable total scores for the Minnesota Living With Heart Failure Questionnaire and the Yale Dyspnea-Fatigue Index. There was no relation between the Living With Heart Failure Questionnaire and peak exercise VO2 and only a weak correlation between the Dyspnea-Fatigue Index and peak VO2 (r = .48). CONCLUSIONS: The level of exercise intolerance perceived by patients with heart failure has little or no relation to objective measures of circulatory, ventilatory, or metabolic dysfunction during exercise. In patients who report severe exertional symptoms, it may be desirable to directly measure hemodynamic response to exercise to ensure that these symptoms are due to circulatory dysfunction.

Adult↗
PubMed1995

Sources of subcortical afferents to the macaque's dorsal lateral geniculate nucleus.

BACKGROUND: The dorsal lateral geniculate nucleus (dLGN) is the thalamic region responsible for transmitting retina signals to cortex. Brainstem pathways to this nucleus have been described in several species and are believed to control the retinocortical pathway depending on the state of the animal (awake, asleep, drowsy, etc.). The purpose of this study was to determine all of the subcortical sources of afferents to the dLGN in a higher primate, the macaque monkey, whose visual system is similar to that of humans. METHODS: Injections of horseradish peroxidase (HRP), with or without conjugation to wheat germ agglutinin, were made into the dLGNs of seven macaque monkeys, followed by perfusion, brain sectioning, and analyses of neurons in the brainstem, thalamus, and hypothalamus that contained the retrogradely transported marker. RESULTS: The reticular nucleus of the thalamus, pedunculopontine nucleus, parabigeminal nucleus, pretectal nucleus of the optic tract, superior colliculus, dorsal raphe nucleus, and tuberomammillary region of the hypothalamus contained many retrogradely labeled neurons ipsilateral to the injections. In the contralateral brainstem, HRP-labeled cells were found only in the pedunculopontine nucleus, nucleus of the optic tract, and dorsal raphe nucleus. The number of labeled neurons on the contralateral side was about one-half of that in corresponding ipsilateral nuclei. The locus coeruleus contained no labeled neurons in four of the macaques that had injections limited to the dLGN. CONCLUSION: There are seven subcortical regions that send afferents to the dLGNs of macaque monkeys. Except for the locus coeruleus, these are the same as observed for other species, such as the cat and rat, and indicate the possible sources of subcortical control over the dLGNs of humans.

Animals↗
PubMed1995

Dissociation between peak exercise oxygen consumption and hemodynamic dysfunction in potential heart transplant candidates.

OBJECTIVES: The purpose of this study was to determine how often peak exercise oxygen consumption (VO2) misclassifies the severity of cardiac dysfunction in potential heart transplant candidates. BACKGROUND: Cardiopulmonary exercise testing is being used to help select heart transplant candidates on the basis of the assumption that a low peak exercise VO2 indicates severe hemodynamic dysfunction and a poor prognosis. However, noncardiac factors, such as muscle deconditioning, can also influence exercise capacity. Therefore, peak exercise VO2 may overestimate the severity of cardiac dysfunction in some patients. METHODS: Hemodynamic and respiratory responses to maximal treadmill exercise were measured in 64 sequential patients undergoing evaluation for heart transplantation, all of whom had an ejection fraction < 35% and reduced peak exercise VO2 levels (mean [+/- SD] 13.3 +/- 2.7 ml/min per kg). RESULTS: Twenty-eight (44%) of 64 patients exhibited a reduced cardiac output response to exercise and pulmonary wedge pressure > 20 mm Hg at peak exercise, consistent with severe hemodynamic dysfunction. Twenty-three patients (36%) exhibited a normal cardiac output response to exercise but a wedge pressure > 20 mm Hg at peak exercise, suggesting moderate hemodynamic dysfunction. Thirteen patients (20%) exhibited a normal cardiac output and wedge pressure < 20 mm Hg at peak exercise, suggesting mild hemodynamic dysfunction. Despite these markedly different hemodynamic responses, all three groups exhibited similar peak exercise VO2 levels (mild dysfunction 14.2 +/- 3.5 ml/min per kg, moderate dysfunction 13.9 +/- 2.7 ml/min per kg, severe dysfunction 12.4 +/- 2.1 ml/min per kg). A peak exercise VO2 level < 14 ml/min per kg, considered to reflect severe hemodynamic dysfunction, was observed in 18 of the patients with a normal cardiac output response to exercise, whereas 7 patients with severe hemodynamic dysfunction had a peak VO2 level > 14 ml/min per kg. CONCLUSIONS: More than 50% of potential heart transplant candidates with a reduced peak exercise VO2 level exhibit only mild or moderate hemodynamic dysfunction during exercise. Hemodynamic responses to exercise should be directly measured in potential transplant candidates to confirm severe circulatory dysfunction.

Adult↗
PubMed1995

Clenbuterol: a substitute for anabolic steroids?

Clenbuterol is a recently popular drug used by athletes in many sports for its purported anabolic effects and reduction of subcutaneous fat. It is a beta-2 (beta 2) agonist prescribed overseas as a bronchodilator, but not approved for use in this country. It is on the banned substance list of the United States Olympic Committee. To avoid any erosion of confidence, physicians caring for athletes need accurate information regarding clenbuterol. Such information is unavailable within the routine medical environs. A review of the literature of animal husbandry reveals that this drug, when administered in doses far greater than those required for bronchodilation, does indeed increase the deposition rate of lean mass and retard adipose gain. There are no human studies available. Animal studies were conducted on laboratory and slaughter stock. No investigation into long-term cardiovascular side effects has been undertaken. The rate of extrapolation from animal studies to unsupervised human usage is alarming. If this category of drugs does preserve lean mass in humans, there are legitimate medical applications. Trials of efficacy and safety are needed.

Adipose Tissue↗
PubMed1995

An alternative oxygen supply technique for the difficult patient.

A modified oxygen delivery system was developed for a patient too claustrophobic for the monoplace chamber or the hood in the multiplace chamber. The adaptation delivered O2 through the patient's tracheostomy by means of a soft cervical collar, a pediatric tracheostomy cuff, and a T-tube.

Atmosphere Exposure Chambers↗
PubMed1994

Sensorimotor neuropathy resembling CIDP in patients receiving FK506.

FK506 is an important immunosuppressant that has shown great promise in the treatment of autoimmune diseases. Approximately 5% of patients receiving FK506 develop major central nervous system toxicity, but the peripheral nerves are usually spared. During 1990-1991, some 1000 patients received liver transplants under FK506 immunosuppression. Of these, 3 patients developed severe multifocal demyelinating sensorimotor polyneuropathy 2-10 weeks after initiation of FK506 therapy. Improvement followed plasmapheresis or intravenous immunoglobulin (IVIG), suggesting an immune-mediated cause. Although autoimmune neuropathy has been previously reported in immune-deficient states such as Hodgkin's disease and AIDS, it is not an expected complication of immunosuppressive therapy. However, others have shown that this phenomenon can be produced in rats with cyclosporine A (CsA), whose effects on T-cell subsets are similar to those seen with FK506. These T-cell subset changes may have precipitated this dysimmune neuropathy in our patients.

Demyelinating Diseases↗
PubMed1994

Aberrant reinnervation following hypoglossal nerve damage.

Hypoglossal nerve damage is a known complication of carotid endarterectomy, occurring in approximately 5% of endarterectomies. The vast majority of these patients recover without functional disability from this injury even if the tongue remains hemiplegic. We report 2 patients who suffered hypoglossal nerve section during neck surgery. Although they were initially mildly symptomatic, they developed increasingly severe dysarthria and dysphagia beginning 4 months after surgery. EMG revealed abnormal coactivation of the genioglossus and styloglossus muscles on the affected side, suggesting aberrant reinnervation. Aberrant reinnervation is a well-known complication of facial nerve injury, but has not been previously recognized in hypoglossal nerve injury. Like the face, the tongue is composed of many muscles that must perform complex movements. Normally, injury to one hypoglossal nerve causes little or no disability, but when aberrant reinnervation occurs, the tongue no longer moves in a coordinated manner, and significant dysarthria ensues.

Aged↗
PubMed1994

Contribution of potassium to exercise-induced vasodilation in humans.

It has been postulated that skeletal muscle release of potassium contributes to exercise-induced vasodilation of skeletal muscle arterioles. To determine whether potassium produces muscle arteriolar vasodilation in humans, we measured plethysmographic forearm blood flow and brachial venous potassium concentrations during brachial arterial infusion of potassium (0.6, 3, 6, 15, and 30 mueq.min-1.100 ml forearm volume-1) in nine normal subjects. Infusion of potassium decreased forearm vascular resistance, with an increase in brachial venous potassium of 1 meq/l decreasing forearm vascular tone by 25-30%. We then measured plasma potassium concentrations during forearm and upright bicycle exercise in 15 normal subjects. Forearm exercise at 0.6 W decreased forearm vascular resistance by 83%, whereas brachial venous potassium increased by only 0.5 +/- 0.2 meq/l (both P < 0.05). Maximal bicycle exercise increased systemic potassium concentrations by 1.2 +/- 0.2 meq/l. These findings indicate that potassium produces muscle arteriolar vasodilation in humans and therefore supports the hypothesis that potassium release from exercising muscle contributes to exercise-induced vasodilation. The relatively small change in venous potassium noted during forearm exercise despite marked forearm vasodilation suggests that local potassium release is only a small contributor to exercise-induced vasodilation. However, potassium release during maximal exercise may have significant vasodilatory effects on arterioles both in exercising and nonexercising tissues.

Adult↗
PubMed1994

Validation of near-infrared spectroscopy in humans.

Near-infrared (NIR) spectroscopy is a noninvasive technique that uses the differential absorption properties of hemoglobin to evaluate skeletal muscle oxygenation. Oxygenated and deoxygenated hemoglobin absorb light equally at 800 nm, whereas at 760 nm absorption is primarily from deoxygenated hemoglobin. Therefore, monitoring these two wavelengths provides an index of deoxygenation. To investigate whether venous oxygen saturation and absorption between 760 and 800 nm (760-800 nm absorption) are correlated, both were measured during forearm exercise. Significant correlations were observed in all subjects (r = 0.92 +/- 0.07; P < 0.05). The contribution of skin flow to the changes in 760-800 nm absorption was investigated by simultaneous measurement of skin flow by laser flow Doppler and NIR recordings during hot water immersion. Changes in skin flow but not 760-800 nm absorption were noted. Intra-arterial infusions of nitroprusside and norepinephrine were performed to study the effect of alteration of muscle perfusion on 760-800 nm absorption. Limb flow was measured with venous plethysmography. Percent oxygenation increased with nitroprusside and decreased with norepinephrine. Finally, the contribution of myoglobin to the 760-800 nm absorption was assessed by using 1H-magnetic resonance spectroscopy. At peak exercise, percent NIR deoxygenation during exercise was 80 +/- 7%, but only one subject exhibited a small deoxygenated myoglobin signal. In conclusion, 760-800 nm absorption is 1) closely correlated with venous oxygen saturation, 2) minimally affected by skin blood flow, 3) altered by changes in limb perfusion, and 4) primarily derived from deoxygenated hemoglobin and not myoglobin.

Absorption↗
PubMed1994

In vivo magnetic resonance spectroscopy measurement of deoxymyoglobin during exercise in patients with heart failure. Demonstration of abnormal muscle metabolism despite adequate oxygenation.

BACKGROUND: Skeletal muscle metabolic abnormalities have been described in patients with heart failure that are independent of total limb perfusion, histochemical changes, and muscle mass. However, these skeletal muscle metabolic abnormalities may result from tissue hypoxia caused by maldistribution of flow. Myoglobin is an O2 binding protein that can indirectly assess tissue hypoxia. METHODS AND RESULTS: In vivo measurement of deoxymyoglobin was performed by use of proton (1H) magnetic resonance spectroscopy in 16 heart failure (HF) (left ventricular ejection fraction = 20 +/- 6%; VO2 = 14.5 +/- 5.1 mL/kg per minute) and 7 healthy (Nl) subjects. Simultaneous phosphorus (31P) magnetic resonance spectroscopy and near-infrared spectroscopy also were obtained to examine muscle metabolism and oxygenation. Supine calf plantarflexion was performed every 4 seconds. Incremental steady-state work was performed. A second exercise protocol studied rapid incremental (RAMP) exercise with plantarflexion every 2 seconds. Arterial occlusion at end exercise provided physiological calibration for myoglobin and hemoglobin signals. With steady-state exercise, the work slope, ie, inorganic phosphorus to phosphocreatine ratios versus work, was significantly greater in patients with heart failure (Nl: 0.18 +/- 0.08; HF: 0.40 +/- 0.32 W-1; P < .05). Intracellular pH was reduced significantly at end exercise in patients but not healthy subjects. Despite these metabolic abnormalities, muscle oxygenation derived from 760- to 850-nm absorption was comparable in both groups throughout exercise. The relation of inorganic phosphorus/phosphocreatine (P1/PCr) ratio and muscle oxygenation was shifted upward in patients with heart failure such that at the same muscle oxygenation, Pi/PCr ratio in these patients was increased. No deoxymyoglobin signals were observed at rest. At maximal exercise, 4 of the healthy subjects and 3 of the patients exhibited deoxymyoglobin (P = NS). With RAMP exercise, the work slope was again significantly greater in patients with heart failure (Nl: 0.21 +/- 0.10; HF: 0.57 +/- 0.32 W-1; P < .05). Intracellular pH again was significantly decreased at end exercise in patients but not healthy subjects. Five of the healthy subjects and 3 of the heart failure patients had deoxymyoglobin signal (P = NS). With arterial occlusion, deoxymyoglobin was seen in all subjects. CONCLUSION: Abnormal skeletal muscle metabolism in patients with heart failure usually occurs in the absence of myoglobin deoxygenation, suggesting that the abnormalities are not a result of cellular hypoxia during exercise with minimal cardiovascular stress.

Aged↗
PubMed1993

Contribution of endothelium-derived relaxing factor to exercise-induced vasodilation in humans.

Release of endothelium-derived relaxing factor (EDRF) from the vascular endothelium may contribute to skeletal muscle arteriolar vasodilation during exercise. The present study was undertaken to test this hypothesis. Ten normal subjects underwent brachial arterial catheter insertion and instrumentation of their forearm to measure plethysmographic forearm blood flow. Forearm blood flow was then measured at rest, during two levels of wrist flexion exercise (0.2 and 0.4 W), and during 0.4-W exercise with concurrent infusion of norepinephrine (100 ng.min-1 x 100 ml forearm volume-1). Measurements were made with and without infusion of N-monomethyl-L-arginine (L-NMMA) (0.1-0.2 mg.min-1 x 100 ml forearm volume-1), a specific inhibitor of EDRF synthesis. Infusion of L-NMMA reduced resting forearm blood flow (control: 2.5 +/- 0.4 vs. L-NMMA: 1.5 +/- 0.1 ml.min-1 x 100 ml-1) and markedly reduced forearm blood flow response to acetylcholine (5 micrograms.min-1 x 100 ml forearm volume-1) (control: 20.2 +/- 2.9 vs L-NMMA: 4.0 +/- 1.0 ml.min-1 x 100 ml-1; both P < 0.01). However, L-NMMA had no significant effect on flow responses to exercise (0.2 W: 8.3 +/- 1.1 vs. 8.3 +/- 1.2; 0.4 W: 13.8 +/- 1.7 vs. 13.5 +/- 1.7; 0.4 W + norepinephrine: 10.3 +/- 2.4 vs. 9.4 +/- 2.6 ml.min-1 x 100 ml-1; all P = NS). These findings suggest that release of EDRF from the vascular endothelium contributes to skeletal muscle arteriolar vasodilation at rest but does not contribute to the arteriolar vasodilation produced by exercise.

Acetylcholine↗
PubMed1992

Detection of skeletal muscle fatigue in patients with heart failure using electromyography.

Patients with heart failure frequently report that leg fatigue limits maximal exercise capacity. However, objective documentation of muscle fatigue has not been obtained in such patients. In normal subjects, muscle fatigue during constant work load exercise is associated with an increase in electrical activity generated per contraction due to use of additional muscle fibers to compensate for fiber fatigue. The present study was performed to determine if this approach can be used to document muscle fatigue in patients with heart failure. Vastus lateralis surface electromyograms were monitored in 8 ambulatory patients with nonedematous heart failure and 6 normal subjects during maximal bicycle exercise (20 W increments every 2 minutes). The electromyogram was stored on tape and subsequently analyzed for integrated root-mean-square voltage/contraction (iRMSV). At each work load, the iRMSV of the first and last 30 seconds of the work load were compared. The maximal work load achieved by patients with heart failure was significantly lower (73 +/- 22 W) than that by normal subjects (150 +/- 15 W; p less than 0.01). Both groups had no significant difference between the initial and final iRMSV at submaximal work loads. However, during the 2 highest work loads, both groups reported leg fatigue and had significant increases in iRMSV, consistent with muscle fiber fatigue (maximal work load: 259 +/- 59 to 279 +/- 58 mv.ms [normals] vs 258 +/- 94 to 283 +/- 93 mv.ms [heart failure]; p less than 0.03). The data indicate that the surface electromyogram can be used to detect skeletal muscle fatigue in patients with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Effects of cardiac transplantation on ventilatory response to exercise.

Patients with heart failure frequently exhibit an excessive ventilatory response to exercise, which is acutely unaltered by therapeutic interventions. To investigate whether these ventilatory responses resolve after cardiac transplantation, 15 ambulatory patients with severe heart failure underwent exercise testing with measurement of respiratory gases before and 1.4 +/- 0.6 years [corrected] after transplantation. Ventilatory response was also measured in 7 age-matched, sedentary control subjects. Left ventricular ejection fraction at rest and hemodynamic measurements were obtained before and after transplantation in all patients. After transplantation, ejection fraction at rest increased from 16 +/- 6 to 56 +/- 10%, pulmonary capillary wedge pressure declined from 26 +/- 8 to 12 +/- 5 mm Hg, and cardiac index increased from 1.7 +/- 0.5 to 2.8 +/- 0.5 liters/min/m2 (all p less than 0.001). Peak oxygen consumption increased from 11.8 +/- 1.9 to 19.2 +/- 3.1 ml/kg/min (p less than 0.001), but remained significantly lower than that in control subjects (33.4 +/- 6.9 ml/kg/min; p less than 0.01). Minute ventilation (VE) was significantly reduced after transplantation, but excessive compared with normal values. Ventilation at a carbon dioxide production of 1 liter/min decreased significantly after cardiac transplantation (52.1 +/- 7.9 to 38.8 +/- 3.8 liters; p less than 0.01), but remained elevated when contrasted to that in control subjects (31.4 +/- 3.4 liters; p less than 0.05). Ventilatory response to exercise is significantly improved after cardiac transplantation; however, VE remains excessive. This may reflect an attenuated cardiac output response to exercise, abnormal intrapulmonary pressures or persistent deconditioning.

Adult↗
PubMed1992

Competition between an aphakic and an occluded eye for territory in striate cortex of developing rhesus monkeys: cytochrome oxidase histochemistry in layer 4C.

Monkey models were used to examine the effects of competition for cortical territory between two eyes which were deprived simultaneously, but each eye experienced a different type of deprivation. We wanted to determine whether, under this condition of binocular unequal deprivation, the postnatal process of segregation into ocular dominance columns proceeds according to the same rules as those that apply to competition between a deprived and an undeprived fellow eye. Our models involved surgical removal of the natural lens from one eye in newborn rhesus monkeys. The resulting aphakia was corrected optically to a near point with extended-wear contact lenses. The fellow eyes were either left unmanipulated or occluded with opaque contact lenses for varying periods during the day. At the end of the rearing period, some monkeys from each experimental group had either one eye enucleated or sustained injury to the retinal ganglion cells of one eye. The histochemical reaction for cytochrome oxidase was used to reveal the widths of ocular dominance columns in layer 4C of striate cortex in these monkeys. Under all experimental conditions, the axons related to the two eyes occupied segregated fields. The amount of cortical territory related to the aphakic, optically corrected eye depended on the manipulations of the fellow eye. In competition with an unmanipulated fellow eye, the aphakic eye's territory was greatly reduced. In competition with a part-time occluded eye, its territory was reduced to a lesser degree, depending on the duration of the occlusion. In competition with a continuously occluded eye, however, the space related to the aphakic, optically corrected eye was slightly greater than that related to the occluded eye. Since neither the aphakic nor the continuously occluded eye receives normal visual input, they are both impaired. Therefore, they may compete on an almost equal basis for synaptic territory in layer 4C of striate cortex. Moreover, it is likely that activities originating in the aphakic and the continuously occluded eye are asynchronous, and that this condition is sufficient to drive the postnatal segregation of inputs from the two deprived eyes.

Aging↗
PubMed1992

Seven generations of genetic selection for ethanol dependence in mice.

An animal model of alcohol dependence is being produced by selecting mice for differences in severity of ethanol withdrawal seizures. Replicate lines of high-dependence (HA), low-dependence (LA), and control (CA) mice are being developed by within-family selection. After seven generations both (replicate) HA and LA lines have separated significantly. Some of the difference between the replicate pairs of HA and LA in the early generations was due to differences in ethanol consumption. This difference in consumption may be attributable to a difference in metabolic rate or activity level rather than to a difference in ethanol preference. Females are more susceptible to seizures than males; this appears to be due partly to their higher consumption of ethanol during treatment.

Alcohol Drinking↗