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Biomedical subjects

R W Russell

Publications and source records attributed to R W Russell.

At least 55 records · Page 3Linked to original sources

Acute cerebral ischaemia: concurrent changes in cerebral blood flow, energy metabolites, pH, and lactate measured with hydrogen clearance and 31P and 1H nuclear magnetic resonance spectroscopy. I. Methodology.

CBF has been measured with the hydrogen clearance technique in the two cerebral hemispheres of the gerbil under halothane anaesthesia. This has been correlated with changes in local pH, tissue lactate, and phosphorus energy metabolites measured in the same animals with 1H and 31P nuclear magnetic resonance (NMR) spectroscopy. The NMR measurements were made with two surface coils, one on each hemisphere. This article describes the experimental details and shows that in acute unilateral or bilateral forebrain ischaemia metabolic changes can be monitored by NMR with no significant interhemispheric cross talk. The metabolic effects of reperfusion are also shown. The model allows the definition of the time course of the metabolic consequences of regional ischaemia and reperfusion in individual laboratory animals.

Acute Disease↗

Acute cerebral ischaemia: concurrent changes in cerebral blood flow, energy metabolites, pH, and lactate measured with hydrogen clearance and 31P and 1H nuclear magnetic resonance spectroscopy. II. Changes during ischaemia.

CBF has been measured with the hydrogen clearance technique in the two cerebral hemispheres of the gerbil under halothane anesthesia. This has been correlated with changes in local pH, tissue lactate, and phosphorus energy metabolites measured in the same animals with 1H and 31P nuclear magnetic resonance spectroscopy. We demonstrate a threshold flow value for the metabolic changes associated with energy failure at a level similar to the values previously reported for electrical failure and tissue water accumulation, but higher than that associated with breakdown of extracellular potassium homeostasis.

Animals↗

Cerebral haemodynamic changes after extracranial-intracranial bypass surgery.

Regional cerebral blood flow, oxygen utilisation, fractional oxygen extraction, and cerebral blood volume were measured by positron emission tomography in twelve patients with carotid artery occlusion. Follow-up studies were carried out at a mean interval of eleven weeks after extracranial-intracranial bypass surgery. Clinical improvement was observed in three patients who had presented with frequent transient ischaemic attacks. One patient with multiple vascular occlusions suffered a stroke at the time of surgery. Follow-up studies showed an increase of regional cerebral blood flow in only two of the twelve patients. In the group as a whole, there was no significant change of cerebral blood flow, oxygen consumption or fractional oxygen extraction after bypass surgery. The most consistent post-operative change, observed in eleven of the twelve patients, was a fall of cerebral blood volume in the cortical territory of the bypassed carotid artery (p less than 0.01). This effect was most marked in patients with bilateral carotid occlusion, in whom there was often an accompanying fall of blood volume in the contralateral hemisphere. The post-operative findings were consistent with an increase of regional cerebral perfusion pressure as a result of the bypass procedure. Although this effect is potentially of value, those patients with most to gain from bypass surgery may also run the highest risk of peri-operative cerebral ischaemia.

Aged↗

Prognosis of patients with retinal embolism.

Eighty-five patients with retinal emboli, visible ophthalmoscopically, were studied retrospectively. All the patients had presented with transient or permanent visual loss. Follow up from the time of presentation was one year to 12 years with a mean of 4.5 years. Life expectancy in the 58 medically treated patients who presented with cholesterol emboli was significantly reduced (p = 0.028). Stroke was the commonest cause of death and was significantly more frequent than in the general population (p less than 0.001); there was also an increased total incidence of cerebrovascular disease (fatal and non-fatal) compared with the Oxfordshire Stroke Project (p less than 0.001). The mortality from ischaemic heart disease was not significantly increased. We report a series of 85 patients with retinal emboli, 69 of whom had cholesterol emboli (70 fundi), 15 calcific emboli and one platelet-fibrin embolus. The natural history of medically treated patients with cholesterol emboli is compared both with an age and sex matched population and with patients with amaurosis fugax but no visible retinal emboli.

Adult↗

Drugs as tools for research in neuropsychobiology: a historical perspective.

Knowledge in neuropsychobiology continues to benefit from the use of drugs as 'tools' to alter neurochemical events as a means of studying interactions between the events and behaviour. Before drugs could play such a role, concepts about basic properties of living organism had to be refined. Techniques had to be invented for investigating the kinetics by which drugs reach their sites of action within the body and the dynamics of their effects once they have occupied their receptors, behaviour being one category of such effects. The present discussion examines these developments in historical perspective, focusing upon influences they have in advancing our understanding of neurochemical substrates of behaviour.

History, 20th Century↗

A flow-limited simulation model of isotopic water dilution.

A model of the kinetics of water metabolism is not synonymous with an anatomic model of body water pools. Quantitating the anatomic relations of pools of body water that are separable on a kinetic basis is very difficult, and these relations are influenced by the physiological state of the animal. A fifteen-pool, flow-limited simulation model of body water distribution and mixing was constructed based on literature values to study the relationship between anatomical and kinetic pools of body water. The blood dilution curve predicted by the model agrees well with dilution curves in the literature. Altering rumen water volume in the model does not alter the blood dilution curve. Segmenting anatomical pools of water on the basis of blood deuterium oxide (D2O) dilution curves is not a realistic goal. Total body water, independent of the physiological state of the animal, can be measured by D2O dilution after isotopic equilibration has been established if corrections are made for the amount of D2O that is lost prior to attaining equilibrium. The model can be used to search for dosing and sampling schemes that have the potential for fractionating anatomical pools of body water. Although the model is not predictive of any particular situation, it does provide a good base for researching kinetics of body water distribution and body composition.

Animals↗

A model hypocholinergic syndrome produced by a false choline analog, N-aminodeanol.

N-aminodeanol is an analog of choline that serves as a less effective substrate in all of its known enzymatic and transport mechanisms. It was utilized to test the hypothesis that the selective vulnerability of cholinergic neurones in Alzheimer's disease is due to competition for the available choline between pathways for acetylcholine and phospholipid synthesis. Rats placed on a choline free diet containing an equivalent amount of N-aminodeanol develop a model hypocholinergic state comprising hyperreactivity, hyperalgesia, aggressive behavior and a deficit in learning and memory. These effects are associated with a progressive replacement of free and lipid-bound choline and acetylcholine with N-aminodeanol and its corresponding esters. Choline acetyltransferase is reduced in some brain regions, suggesting a loss of cholinergic neurones. We propose that this represents a potentially useful animal model of Alzheimer's disease which deserves further investigation.

Alzheimer Disease↗

Use of in vivo kinetic techniques to evaluate metabolism of nutrients.

Most nutrition research is related to rates of physiological processes. Information about those processes can be gained by in vivo kinetic techniques; however, many nutritionists are hesitant to use in vivo kinetics. The two basic in vivo kinetic techniques are single injection and continuous infusion of tracer into a pool of tracee. Either technique can form the basis for multiple-pool kinetics, or modeling. Solving a multiple-pool system can provide flow rates of substances between metabolic pools and is valuable for understanding a particular metabolic pathway or process. In vivo kinetic techniques can be valuable in understanding mechanisms whereby partitioning agents affect the distribution of nutrients, especially protein and fat, in food-producing animals. In vivo kinetics is a valuable tool for nutrition research and should be used more frequently.

Animal Nutritional Physiological Phenomena↗

Behavioral and physiological effects associated with changes in muscarinic receptors following administration of an irreversible cholinergic agonist (BM 123).

Previous work in our laboratory has shown that the aziridinium ion of BM 123 (N-[4(2-chloroethylmethylamino)-2-butynyl]-2 pyrrolidone) is a potent and selective muscarinic agonist and binds irreversibly to muscarinic receptors (mAChR). The present series of experiments was designed to study the effects of BM 123 on behavioral and physiological variables known to be sensitive to manipulations of the cholinergic neurotransmitter system. BM 123 was injected into the tail vein of Sprague-Dawley rats, reducing mAChR to approximately 10% of normal as judged by [3H](-)QNB binding. Oxotremorine was injected IV for purposes of comparison. Behavioral and physiological variables were measured daily for 26 days. Physiological variables (e.g., tremor, chromodacryorrhea, salivation, and temperature) showed effects in less than 5 min after injection and returned to their pretreatment baselines within minutes. Nociceptive thresholds, dependent on sensory-perceptual processes, showed peak changes of approximately +230% and returned to normal within hours. Motoric responses, i.e., drinking and general activity, recovered in 3-4 days. Learned responses and those requiring temporal discrimination took 8-11 days to recover and were the only responses paralleling the return of the mAChRs to their normal levels. Changes elicited by oxotremorine recovered more rapidly than those elicited by BM 123. The results suggest that the different variables measured are dependent on different densities of functional receptors. Implications for a theoretical model are discussed.

Animals↗

Behavioral and physiological effects of an aziridinium analog of oxotremorine (BM130).

When injected IV BM130, a mustard analog of oxotremorine, acts initially as a cholinergic agonist and thereafter produces a sustained resistance to muscarinic agonists. Control subjects were injected with saline or with BM130A, the active aziridinium intermediate of BM130. Acute injections of BM130 were followed initially by effects that were characteristically cholinomimetic in nature: e.g., tremor, chromodacryorrhea, salivation, hypothermia. The effects were dose-dependent and of limited duration. They were not seen in behavioral variables measured 30 min after drug treatment. Injection of BM130A produced peripheral, but not central effects; saline had no effects. The prediction that initial cholinomimetic effects should be followed by sustained resistance to cholinergic agonists was tested by subjecting animals to oxotremorine challenges at weekly intervals following single injections of BM130. In none of the measures taken did animals injected with BM130A or saline show resistance to the muscarinic challenges. Those administered BM130 showed resistance, which in some variables was sustained for 3-4 weeks. The resistance was statistically significant at high BM130 doses and appeared to be dose dependent over the range studied.

Animals↗

Relation between behaviorally augmented tolerance and upregulation of muscarinic receptors in the CNS: effects of chronic administration of chronic administration of scopolamine.

The present experiment was planned to provide information about relations between behaviorally augmented tolerance and accompanying upregulation of muscarinic receptors (mAChR) (physiological tolerance) in the CNS during chronic administration of the cholinergic antagonist scopolamine. Analyses of the data on mAChR binding established significant upregulation (Bmax) had occurred in the cortex, hippocampus, and striatum of animals treated with scopolamine, but not of those in the saline or methylscopolamine groups. There were no treatment effects in affinity (KD). The effect of scopolamine administered before a behavioral test session was to cause an acute decrease in FR5 responding to water reinforcement, and hence in resulting water consumption. Animals immediately compensated for this decrement by higher response rates during a free drinking (FDR) period which followed. When scopolamine was injected between the FR5 and FDR periods, FR5 responding increased to compensate for the drug's effect on the FDR. There was evidence that physiological tolerance also occurred as indicated by a more slowly developing trend toward recovery of levels of behavioral responding related to mAChR upregulation, although full recovery to pretreatment baselines did not occur within the 25 days of chronic treatments. The results as a whole are consistent with a multifactorial model of tolerance development, to which both behavioral and neurochemical processes contribute.

Animals↗

Effects of body size on kinetics of glucose metabolism and on nitrogen balance in growing cattle.

Effects of body size on the kinetics of glucose metabolism were examined. In trial 1, steers were fed 6 kg of an 80:20 concentrate:roughage diet daily across a weight range of 226 to 470 kg. In trial 2, steers were fed 4.5 kg of a 45:55 concentrate:roughage diet daily across a weight range of 134 to 390 kg. Glucose irreversible loss averaged 820 +/- 32 and 461 +/- 13 mg/min for trials 1 and 2 and was not affected by body size. Thus, glucose irreversible loss seems to be regulated by feed intake when intake is above maintenance. Body size had no effect on glucose total entry rate, recycling or pool size. Blood glucose concentration and glucose space decreased at 0.004 mg X ml-1 X kg-1 and 0.002 fractional units body wt X kg-1 as body size increased. Digestible energy and nitrogen balance were measured in trial 2. Digestibility of energy increased at 0.0054 Mcal X d-1 X kg-1 as body size increased. Nitrogen retention averaged 28.2 g X d-1 and was not influenced by body size even though energy intake approached maintenance amounts at the end of the trial. On the basis of urinary nitrogen excretion data, we conclude that the maximum net contribution of amino acid carbon to glucose synthesis was 8% of glucose carbon.

Absorption↗

Clinical and electrophysiological observations in patients with low pressure retinopathy.

The clinical, angiographic, and electrophysiological features of seven patients with transient visual loss and low-pressure retinopathy are presented. Six of the patients also had symptoms of cerebral ischaemia. The commonest provoking feature was bright light. Angiography showed multiple extracranial occlusions involving both internal and external carotid arteries in addition to occlusion or stenosis on the contralateral side. Electroretinography showed delay in the recovery of the b wave in the affected eye after exposure to bright light. This appears to be a valuable test for the detection of minor degrees of ischaemic damage to the retina caused by insufficiency of the retinal and choroidal circulation.

Aged↗

Reactivity of the cerebral circulation in patients with carotid occlusion.

Cerebral blood flow (CBF) and the response to hypercapnia (cerebral reactivity) have been measured in 41 patients with unilateral or bilateral internal carotid artery occlusion in an attempt to identify those with limited collateral reserve. Normocapnic CBF was within normal limits in the majority of subjects. The response to hypercapnia varied from normal to absent, with impaired reactivity becoming increasingly likely when more than one artery was diseased. In 19 patients with unilateral carotid occlusion, hemisphere reactivity was well preserved in the majority, but was significantly lower on the side of the occlusion (mean 2.9%/mm Hg) compared to the normal side (mean 3.4%/mm Hg). Reactivity on the side of the occlusion was further reduced in 15 patients with occlusion and contralateral internal carotid artery stenosis (mean 1.7%/mm Hg) and was even lower in seven patients with bilateral occlusion (mean 1.1%/mm Hg). There was no difference in reactivity between asymptomatic hemispheres in the 41 patients (mean 2.7%/mm Hg) and hemispheres in which a previous stroke had occurred (mean 2.8%/mm Hg). In contrast the response in hemispheres subject to continuing transient ischaemic attacks was significantly impaired (mean 1.6%/mm Hg), suggesting that the cerebral symptoms in some of these patients may have had a haemodynamic origin more often than suspected from the clinical history.

Aged↗

Fluorescein angiography in carotid disease.

Twenty four cases in whom occlusive disease of the carotid artery was proven by digital subtraction angiography or direct carotid arteriography were studied. In five cases venous stasis retinopathy was evident ophthalmoscopically. Fluorescein angiography was abnormal in 19 cases. The abnormalities found were microaneurysms (16 cases); slow arteriovenous transit time (8 cases); macular oedema (8 cases); leakage from the arterioles (3 cases); disc new vessels (4 cases). The differences between this retinopathy and diabetic retinopathy are discussed.

Adult↗

Effect of treatment with botulinum toxin on neurogenic blepharospasm.

Botulinum toxin type A creates temporary localised flaccid paralysis after injection into skeletal muscle. Thirty four patients with blepharospasm, of whom 28 also had the oromandibular dystonia syndrome, were treated with injections of botulinum toxin type A into the orbicularis oculi, and 28 showed functional improvement after the treatment. A high incidence of local side effects occurred, especially partial ptosis, which was well tolerated. There were no systemic side effects. The average period of relief was 2.5 months, increasing to 2.8 months after a second injection. Functional improvement was limited in patients with severe associated dystonia.

Adult↗

Effects of acute food and/or water deprivation on muricide.

The present experiment was designed to test certain predictions derived from models of interactions between muricide and appetitive behaviors proposed earlier by Russell and Singer [8,9]. One of the major features of the models centered on whether the two types of behavior are inevitably related. The general design of the present experiment involved testing for muricide either (a) after deprivation of food and/or water or (b) at times during the normal diurnal cycle when the two consummatory responses were at their minima and maxima. Deprivation and testing for muricide were limited to a single episode in order to eliminate confounding effects of repeated deprivations and of repeated exposures to prey. Periods of acute deprivation ranging from 5.5 to 22.0 hr did not induce significant quantitative changes in muricidal behavior. However, muricide and the appetitive behaviors did co-vary under conditions associated with the normal diurnal cycle. Comparing the present results with findings from experiments using repeated deprivation leads to the suggestion that covariation of appetitive and muricidal behaviors is not an innate characteristic, but rather is acquired through processes of learning. Present results further suggest that each of the two types of behavior has its own physiological substrate which can be modified independently, but also may be activated concomitantly by a common set of antecedent conditions.

Aggression↗