In defence of an outpost of Empire: Sister Radcliff goes to Gallipoli.
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Australia↗
Biomedical subjects
J R Wilson
Publications and source records attributed to J R Wilson.
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↗
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↗
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↗
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↗
Colonic cancer cell (HT29) adhesion to laminin is altered by differentiation: adhesion may involve galactosyltransferase.
The effects of cell differentiation on cell adhesion to laminin were studied using the human colon tumor cell line, HT29. HT29 cells were induced to differentiate either by glucose deprivation (HT29glc- vs HT29glc+) or by 2 mM butyrate (HT29glc-+B+). Adhesion was assayed after incubating cell suspensions in microtiter wells previously coated with laminin or other substrates. HT29glc+ cells adhered preferentially to laminin over BSA, fibronectin, and ovalbumin. The adhesion to laminin was greater than 50% of maximum within 15 min. HT29glc- cell adhesion to laminin was consistently lower than that for HT29glc+ or HT29glc+B+ cells. alpha-Lactalbumin (ALA), a modifier of galactosyltransferase (GT) substrate specificity, caused a significant reduction (greater than 50%) in HT29glc+ cell adhesion to laminin when ALA was added to the adhesion incubation mixture. Addition of glucose+ALA to the suspension restored adhesion to laminin. Ovalbumin, a GT substrate, increased adhesion of HT29glc+ and HT29glc- cells to laminin, but lactose, a GT product, did not. The data show that undifferentiated HT29 cells adhere preferentially to laminin over fibronectin and collagen IV and that differentiation of HT29 cells reduces adhesion to laminin. In addition, the data imply that cell adhesion to laminin may be mediated by factors that also modify galactosyltransferase activity.
Butyrates↗
Use of allopurinol and deferoxamine in cellular protection during ischemia.
During cellular ischemia and death, many changes occur in the cell. These include the build-up of purines and lipid peroxidation. In this study, we evaluated the effectiveness of allopurinol, which blocks purine breakdown, and deferoxamine, which inhibits lipid peroxidation, as cytoprotective agents. Rats were subjected to middle cerebral artery occlusion and were treated with high or low doses of allopurinol or high or low doses of deferoxamine, with normal saline used as a control. Treatments were given 1 hour before, 1 hour after, or 5 hours after occlusion. The outcome was based on neurological status and infarct size. Both infarct size and neurological status were found to be improved in all treatment groups when compared to controls. This study suggests that the use of these agents prevents cellular damage during ischemia.
Allopurinol↗
The pathway of arginine catabolism in Giardia intestinalis.
In Giardia intestinalis, arginine is catabolised by the arginine dihydrolase pathway. The enzymes of the pathway (arginine deiminase, ornithine transcarbamoylase and carbamate kinase) were investigated and their basic kinetic parameters determined. The specific activity of arginine deiminase was 270 +/- 23 nmol min-1 (mg protein)-1; ornithine transcarbamoylase, in the direction of citrulline utilisation 170 +/- 22 nmol min-1 (mg protein)-1, and in the direction of ornithine utilisation 2100 +/- 100 nmol min-1 (mg protein)-1; and carbamate kinase 2100 +/- 400 nmol min-1 (mg protein)-1. The activities of these enzymes are between 10 and 250 fold greater than those reported for the enzymes in Trichomonas vaginalis, the only other parasite in which the arginine dihydrolase pathway has been reported. The flux through the pathway in G. intestinalis, as determined by the liberation of 14CO2 from 1 mM [14C-guanidino]arginine was 30 nmol min-1 (mg protein)-1. This flux was not affected by valinomycin (0.1 microM), nigericin (3 microM), azide (5 mM) or cyanide (1 mM). The flux was only marginally affected by glucose up to 10 mM concentration. Conversely, the flux through glucose metabolism, as determined by the release of 14CO2 from 1 mM [1-14C]glucose was only 2 nmol min-1 (mg protein)-1, and was unaffected by arginine concentrations up to 10 mM. These observations suggest that there is no direct metabolic interface between arginine and glucose catabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effect of heart failure on skeletal muscle in dogs.
To investigate the effect of heart failure (HF) on skeletal muscle, gracilis, gastrocnemius, and triceps muscle histochemistry and enzyme activity, gracilis muscle performance, and gracilis muscle 31P magnetic resonance spectroscopy (MRS) metabolic responses to exercise were compared in six sham-operated control dogs (C) and seven dogs with HF produced by 3 mo of rapid ventricular pacing. HF reduced skeletal muscle weights and decreased type II fiber area (3,315 +/- 996 to 1,750 +/- 638 microns 2; P less than 0.01). Citrate synthase and beta-hydroxyacyl CoA dehydrogenase activity also tended to decrease. Gracilis muscle inorganic phosphate-to-phosphocreatine ratios, oxygen uptake (VO2), and pH responses to exercise using supramaximal twitch stimulation, a form of exercise that produces maximal stimulation of all muscle fibers and therefore is independent of muscle mass, were similar in both groups. There was no significant difference in developed tension per gram muscle during stimulation at 0.5-200 Hz, maximal developed tension (C: 177 +/- 32 vs. HF: 173 +/- 44 g/g muscle), or muscle fatigability as assessed by percent of initial tension observed at the end of 2 min of 20 Hz stimulation (C: 52 +/- 17% vs. HF: 52 +/- 11%; all P = NS). These data suggest that HF produces skeletal muscle atrophy but that the remaining muscle exhibits normal performance and metabolism.
Animals↗
Effect of chronic left ventricular failure on beta-endorphin.
Stimulation of endogenous opiate secretion worsens circulatory dysfunction in several forms of shock, in part by inhibiting sympathetic activity. To investigate whether endogenous opiates have a similar effect in chronic heart failure (HF), we measured beta-endorphin concentrations and hemodynamic responses to naloxone infusion (2 mg/kg bolus + 2 mg.kg-1 x h-1) in six control (C) dogs and eight dogs with low-output HF produced by 3 wk of rapid ventricular pacing. The dogs with HF exhibited reduced arterial blood pressure (C, 123 +/- 4 vs. HF, 85 +/- 7 mmHg; P < 0.01) and cardiac outputs (C, 179 +/- 14 vs. HF, 76 +/- 2 ml.min-1 x kg-1; P < 0.01) and elevated plasma norepinephrine concentrations (C, 99 +/- 12 vs. HF, 996 +/- 178 pg/ml; P < 0.01) but normal beta-endorphin concentrations (C, 30 +/- 11 vs. HF, 34 +/- 12 pg/ml; P = NS). Naloxone produced similar transitory increases in blood pressure (C, 14 +/- 5 vs. HF, 26 +/- 25%) and cardiac output (C, 37 +/- 13 vs. HF, 22 +/- 15%) in both groups (both P = NS). No significant changes in norepinephrine concentration or systemic vascular resistance were observed in either group. These findings suggest that beta-endorphin secretion does not exacerbate circulatory dysfunction in chronic heart failure.
Adrenocorticotropic Hormone↗
Contribution of skeletal muscle atrophy to exercise intolerance and altered muscle metabolism in heart failure.
BACKGROUND: The purpose of this study was to investigate the prevalence of skeletal muscle atrophy and its relation to exercise intolerance and abnormal muscle metabolism in patients with heart failure (HF). METHODS AND RESULTS: Peak VO2, percent ideal body weight (% IBW), 24-hour urine creatinine (Cr), and anthropometrics were measured in 62 ambulatory patients with HF. 31P magnetic resonance spectroscopy (MRS) and imaging (MRI) of the calf were performed in 15 patients with HF and 10 control subjects. Inorganic phosphorus (Pi), phosphocreatine (PCr), and intracellular pH were measured at rest and during exercise. Calf muscle volume was determined from the sum of the integrated area of muscle in 1-cm-thick contiguous axial images from the patella to the calcaneus. A reduced skeletal muscle mass was noted in 68% of patients, as evidenced by a decrease in Cr-to-height ratio of less than 7.4 mg/cm and/or upper arm circumference of less than 5% of normal. Calf muscle volume (MRI) was also reduced in the patients with HF (controls, 675 +/- 84 cm3/m2; HF, 567 +/- 112 cm3/m2; p less than 0.05). Fat stores were largely preserved with triceps skinfold of less than 5% of normal and/or IBW of less than 80% in only 8% of patients. Modest linear correlations were observed between peak VO2 and both calf muscle volume per meter squared (r = 0.48) and midarm muscle area (r = 0.36) (both p less than 0.05). 31P metabolic abnormalities during exercise were observed in the patients with HF, which is consistent with intrinsic oxidative abnormalities. The metabolic changes were weakly correlated with muscle volume (r = -0.42, p less than 0.05). CONCLUSIONS: These findings indicate that patients with chronic HF frequently develop significant skeletal muscle atrophy and metabolic abnormalities. Atrophy contributes modestly to both the reduced exercise capacity and altered muscle metabolism.
Exercise↗
New insights into airway inflammation by endobronchial biopsy.
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Administration, Inhalation↗
Effects of monocular deprivation on the visual fields of squirrel monkeys.
Five squirrel monkeys were monocularly deprived at birth for 3 years. Visual field testing for the deprived eye revealed no responses to visual stimuli at any position, including the monocular segment. These results are similar to those obtained in macaque monkeys after long-term neonatal monocular deprivation and indicate that lack of patterned visual input to an eye during development in primates can produce functional blindness throughout the visual field. Because the monocular segment of the visual field was not spared, binocular competition cannot be the only mechanism underlying this loss. Instead, lack of patterned visual input probably causes improper neuronal connections during development in all segments of the visual cortex resulting in complete loss of form vision.
Animals↗
Respiratory muscle deoxygenation during exercise in patients with heart failure demonstrated with near-infrared spectroscopy.
Exertional dyspnea in patients with heart failure may be due, in part, to respiratory muscle underperfusion. Near-infrared spectroscopy is a new technique that permits noninvasive assessment of skeletal muscle oxygenation by monitoring changes in near-infrared light absorption. With use of near-infrared spectroscopy, serratus anterior muscle oxygenation during maximal bicycle exercise was compared in 10 patients with heart failure (ejection fraction 16 +/- 5%) and 7 age-matched normal subjects. Oxygen consumption (VO2), minute ventilation (VE) and arterial saturation were also measured. Changes in difference in absorption between 760 and 800 nm, expressed in arbitrary units, were used to detect muscle deoxygenation. Minimal change in this difference in absorption occurred in normal subjects during exercise, whereas patients with heart failure exhibited progressive changes throughout exercise consistent with respiratory muscle deoxygenation (peak exercise: normal 3 +/- 6, heart failure 12 +/- 4 near-infrared arbitrary units, p less than 0.001). At comparable work loads patients with heart failure had significantly greater minute ventilation and respiratory rate but similar tidal volume when contrasted with normal subjects. However, at peak exercise normal subjects achieved significantly greater minute ventilation and tidal volume with a comparable respiratory rate. No significant arterial desaturation occurred during exercise in either group. These findings indicate that respiratory muscle deoxygenation occurs in patients with heart failure during exercise. This deoxygenation may contribute to the exertional dyspnea experienced by such patients.
Dyspnea↗
Train versus pedestrian accidents.
Railroad-related trauma has been associated with injuries causing considerable morbidity. This is a retrospective study of 15 consecutive patients who were run over by trains. The initial injury produced a traumatic amputation of 10 extremities in eight patients. Limb salvage in two other patients with severe fractures failed, and subsequent lower extremity amputation was required. Despite efforts to salvage the most distal tissue possible, 8 of 12 extremities amputated in the acute traumatic period required revision to a more proximal level. Alcohol ingestion was involved in 13 of the 15 incidents in the study. No patient received posthospitalization alcohol rehabilitation. In addition, despite the young age of the patients in this series, only one patient was rehabilitated to a prosthetic ambulator.
Accidents↗
Impulsivity, sensation seeking, and behavioral and emotional responses to alcohol.
Three hundred forty-two male and female subjects from the Colorado Alcohol Research on Twins and Adoptees returned a mailed questionnaire that included the Eysenck Impulsivity-Venturesomeness-Empathy scales. These subjects had previously been tested in a procedure in which they were given a 0.8 g/kg dose of ethanol to bring their peak blood alcohol concentration (BAC) to near 0.10 g/dl, given topping doses to maintain this BAC over a 3-hr period, and repeatedly tested on a battery of diverse physiological, psychomotor, perceptual speed, and mood measures. Impulsivity was significantly correlated with higher levels of self-reported alcohol use and the occurrence of alcohol use problems in males, while both impulsivity and venturesomeness (sensation seeking) were significantly correlated with lessened motor impairment following alcohol use in males. These personality measures, however, were not significantly correlated with mood measures following initial alcohol dosing. Impulsivity and venturesomeness were uncorrelated with alcohol use and responses to alcohol in females, but as with males, impulsivity was related to the occurrence of alcohol use problems in females.
Adult↗
Effects of aphakia on the geniculostriate system of infant rhesus monkeys.
The effects on the visual system of rearing rhesus monkeys with monocular aphakia, corrected with extended-wear contact lenses, were assessed with anatomical, electrophysiological and behavioral methods. The major finding was that the effects of the various treatments on the aphakic eye varied in degree depending upon the amount of focused pattern input received by the aphakic eye compared to its fellow eye. The behavioral, electrophysiological and anatomical assessments of the treatment effects on the aphakic eyes correlated closely with each other. Because this experimental paradigm is similar to current clinical procedures for treating human infantile monocular cataracts, it provides a nonhuman primate model for studying aphakia.
Animals↗
Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure.
BACKGROUND: Optimal timing of cardiac transplantation in ambulatory patients with severe left ventricular dysfunction is often difficult. To determine whether measurement of peak oxygen consumption (VO2) during maximal exercise testing can be used to identify patients in whom transplantation can be safely deferred, we prospectively performed exercise testing on all ambulatory patients referred for transplant between October 1986 and December 1989. METHODS AND RESULTS: Patients were assigned into one of three groups on the basis of exercise data: Group 1 (n = 35) comprised patients accepted for transplant (VO2 less than or equal to 14 ml/kg/min); group 2 (n = 52) comprised patients considered too well for transplant (VO2 greater than 14 ml/kg/min); and group 3 (n = 27) comprised patients with low VO2 rejected for transplant due to noncardiac problems. All three groups were comparable in New York Heart Association functional class, ejection fraction, and cardiac index (p = NS). Pulmonary capillary wedge pressure was significantly lower in group 2 than in either group 1 or 3 (p less than 0.05), although there was wide overlap. Patients with preserved exercise capacity (group 2) had cumulative 1- and 2-year survival rates of 94% and 84%, which are equal to survival levels after transplantation. In contrast, patients rejected for transplant (group 3) had survival rates of only 47% at 1 year and 32% at 2 years, whereas patients awaiting transplantation (group 1) had a survival rate of 70% at 1 year (both p less than 0.005 versus patients with VO2 greater than 14 ml/kg/min). All deaths in group 2 were sudden. By univariate and multivariate analyses, peak VO2 was the best predictor of survival, with only pulmonary capillary wedge pressure providing additional prognostic information. CONCLUSIONS: These data suggest that cardiac transplantation can be safely deferred in ambulatory patients with severe left ventricular dysfunction and peak exercise VO2 of more than 14 ml/min/kg.
Evaluation Studies as Topic↗