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Biomedical subjects

B G Cooper

Publications and source records attributed to B G Cooper.

32 records · Page 2Linked to original sources

Effect of increased free fatty acid supply on glucose metabolism and skeletal muscle glycogen synthase activity in normal man.

1. Experimental elevation of plasma non-esterified fatty acid concentrations has been postulated to decrease insulin-stimulated glucose oxidation and storage rates. Possible mechanisms were examined by measuring skeletal muscle glycogen synthase activity and muscle glycogen content before and during hyperinsulinaemia while fasting plasma non-esterified fatty acid levels were maintained. 2. Fasting plasma non-esterified fatty acid levels were maintained in seven healthy male subjects by infusion of 20% (w/v) Intralipid (1 ml/min) for 120 min before and during a 240 min hyperinsulinaemic euglycaemic clamp (100 m-units h-1 kg-1) combined with indirect calorimetry. On the control day, 0.154 mol/l NaCl was infused. Vastus lateralis muscle biopsy was performed before and at the end of the insulin infusion. 3. On the Intralipid study day serum triacylglycerol (2.24 +/- 0.20 versus 0.67 +/- 0.10 mmol/l), plasma nonesterified fatty acid (395 +/- 13 versus 51 +/- 1 mumol/l), blood glycerol (152 +/- 2 versus 11 +/- 1 mumol/l) and blood 3-hydroxybutyrate clamp levels [mean (95% confidence interval)] [81 (64-104) versus 4 (3-5) mumol/l] were all significantly higher (all P less than 0.001) than on the control study day. Lipid oxidation rates were also elevated (1.07 +/- 0.07 versus 0.27 +/- 0.08 mg min-1 kg-1, P less than 0.001). During the clamp with Intralipid infusion, insulin-stimulated whole-body glucose disposal decreased by 28% (from 8.53 +/- 0.77 to 6.17 +/- 0.71 mg min-1 kg-1, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗

Lipid and lipoprotein metabolism in familial combined hyperlipidaemia during treatment of sporadic phaeochromocytoma: a case study.

Lipid metabolism was evaluated during management of phaeochromocytoma in a 41 year old non-obese post-menopausal women with familial combined hyperlipidaemia. The main effect of the excess catecholamine secretion on lipid metabolism was increased lipolytic activity, lower serum triglyceride and increased HDL cholesterol concentrations, compared with findings following removal of the tumour. Before removal of the tumour, the use of beta blockers alone led to marked deterioration of the hyperlipidaemic state, and combined alpha and beta blockade additionally led to a marked reduction in fat oxidation and lipoprotein lipase activity. Overactivity of the adrenergic system leads to changes in lipid metabolism in phaeochromocytoma. Treatment of the phaeochromocytoma may lead to worsening of hyperlipidaemia pre-existing in such individuals.

Adrenal Gland Neoplasms↗

Role of plasma non-esterified fatty acids during and after exercise.

1. The importance of circulating non-esterified fatty acids as a substrate during and after low-grade exercise has been examined by using a nicotinic acid analogue to inhibit lipolysis. Seven healthy men received acipimox or placebo on separate occasions. After 90 min, bicycle exercise was performed for 45 min (40% of pre-determined maximum oxygen uptake), followed by a 60 min recovery period. 2. The plasma concentration of non-esterified fatty acids increased during exercise after placebo (320 +/- 80 to 630 +/- 110 mumol/l) and remained elevated in the post-exercise period. Basal concentrations were lower after acipimox (100 +/- 10 mumol/l; P less than 0.05); they declined to 60 +/- 10 mumol/l during exercise and remained at this level for the rest of the study. 3. Lipid oxidation increased from 0.8 +/- 0.1 to 4.2 +/- 0.5 mg min-1 kg-1 during exercise after placebo (P less than 0.001) and remained elevated in the post-exercise period (1.2 +/- 0.1 mg min-1 kg-1). It was lower after acipimox, but still increased from 0.3 +/- 0.1 to 2.3 +/- 0.2 mg min-1 kg-1 with exercise. Carbohydrate oxidation was increased after acipimox compared with after placebo, but only reached significance during the post-exercise period (P less than 0.05). 4. Although acipimox abolished the rise in the plasma concentration of non-esterified fatty acids during exercise, there was only a 50% decrease in the rate of lipid oxidation. This suggests that an alternative source of non-esterified fatty acids makes an important contribution to the supply of lipid for oxidation during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

An evaluation of the Deltatrac indirect calorimeter by gravimetric injection and alcohol burning.

We evaluated a 'state of the art' open hood type of indirect calorimeter (Deltatrac, Datex) to determine its stability and precision, and related these to in vivo measurements made with the same type of calorimeter. Three Deltatrac Metabolic Monitors were investigated at two centres over a period of twelve months by two methods of recovery: (i) gravimetric injection of a nitrogen/CO2 gas mix and (ii) ethanol burning using the manufacturers approved apparatus. We compared machine variation with in vivo variation in measurements of oxygen uptake and carbon dioxide production at rest in healthy subjects. The Deltatrac recovery of both oxygen and carbon dioxide was on average 4.8% and 4.7% higher respectively for the alcohol burning method. We suspected that this apparent over-recovery was because the alcohol burner produced a resistance to the airflow generated across the canopy. By gravimetrically injecting the gas mix into the canopy hose whilst the alcohol burner was attached we were able to confirm this error. There was no significant change in recovery for any of the Deltatracs by either method over the year of evaluation. The between-study variation for the machine and in vivo measurements were less than 4%, and the within-study variations were less than 6% and less than 7%, respectively. These studies re-emphasise that careful evaluation of commercially produced indirect calorimeters is essential before clinical measurements are made.

Calorimetry↗

A video system for investigating breathing disorders during sleep.

A system has been developed for investigating breathing during sleep that superimposes physiological signals on a video image of the patient, with the combined image plus sound recorded on video tape for later analysis. Signals normally displayed include oxygen saturation, airflow, chest wall motion, electroencephalogram, and electrooculogram; but others can be recorded if desired. The information is displayed on a timebase appropriate for the recognition and analysis of respiratory events during sleep. In addition, use is made of normally invisible video lines to record the analogue voltage waveforms so that on replay this information can be displayed on a fast timebase for analysing the more rapidly changing waveforms of electrophysiological signals. The system allows detailed polysomnography to be performed in the normal ward setting with the subject monitored overnight by the nursing staff. Subsequent analysis of the synchronised video, audio, and analogue signals allows measurement of the conventional indices obtained by polysomnography and aids their interpretation.

Humans↗

Value of nocturnal oxygen saturation as a screening test for sleep apnoea.

The sensitivity and specificity of overnight recording of arterial oxygen saturation (SaO2) in routine clinical practice was evaluated in 41 subjects who were being investigated for possible sleep apnoea-hypopnoea syndrome. SaO2 was measured with an ear probe oximeter (Biox IIa) and chart recorder during an "acclimatisation" night immediately before a detailed polysomnographic study. The recordings were classified by two observers as positive, negative, or uninterpretable. Twelve of the 41 patients had the obstructive sleep apnoea syndrome when defined in terms of an apnoea-hypopnoea index greater than 15 events an hour on the second night. The sensitivity of nocturnal SaO2 on the acclimatisation night when the diagnostic criterion was an apnoea-hypopnoea index of greater than 5, greater than 15, and greater than 25/h was 60%, 75%, and 100% respectively. Corresponding values for specificity were 95%, 86%, and 80%. Oximetry alone therefore allowed recognition of a moderate or severe sleep apnoea syndrome. In routine practice an appreciable number of equivocal results is likely and repeat oximetry or more detailed polysomnography will then be required if clinical suspicion is high.

Evaluation Studies as Topic↗

Breathing during sleep in patients with myotonic dystrophy and non-myotonic respiratory muscle weakness.

Sleep apnoea and hypopnoea have been reported in myotonic dystrophy, but it is unclear whether this is simply attributable to the respiratory muscle weakness which is common in this condition. We therefore investigated whether breathing and oxygenation during sleep were more abnormal in patients with myotonic dystrophy than in patients with non-myotonic muscle weakness. Seven subjects were studied in each of three groups: normal controls, myotonic dystrophy and non-myotonic weakness. Patients in the latter group were chosen to represent a similar range of severity of respiratory muscle weakness to those with myotonic dystrophy. Detailed polysomnography was performed; the severity of breathing disorders during sleep was quantified in terms of the frequencies of apnoea and hypopnoea and the degree of arterial desaturation. The myotonic patients showed more frequent apnoea and hypopnoea and more severe desaturation than the other two groups; the results in the non-myotonic patients were generally intermediate. The results suggest that abnormal breathing during sleep is common in myotonic dystrophy and is not due solely to the direct effects of respiratory muscle weakness. Somnolence, which is a well recognized symptom of myotonic dystrophy, was not clearly attributable to the sleep apnoea/hypopnoea syndrome nor to abnormal sleep architecture in the myotonic patients.

Adult↗

Lung function in patients with diabetes mellitus.

Lung function was assessed in 35 nonsmoking adults with insulin dependent diabetes mellitus and 34 matched control subjects. The tests included spirometry, lung volumes, CO transfer factor and maximum respiratory pressures. Additionally, in subjects under 35 years of age (20 patients and 18 controls) measurements of CO transfer factor were obtained during exercise at three different workloads. Random blood glucose and glycosylated haemoglobin were measured and each patient's diabetic history was recorded. The total lung capacity (TLC) in the patients was lower than those recorded for the controls (P less than 0.05) but there were no significant differences in respiratory muscle strength between the groups. In the young group of patients (less than 35 years) the transfer factor for CO (TLCO) was similar but the volume corrected transfer coefficient (KCO) was higher at rest than in the controls (P less than 0.02). The KCO remained high in these patients during exercise. The older patients (greater than 35 years) showed a lower TLCO (P less than 0.01) with a similar KCO to the controls. The association of a reduction in TLC and higher KCO in the young patients suggests an extrapulmonary mechanism of lung volume restriction. This is not attributable to muscle weakness but might be due to limited expansion of the rib cage. In older patients any tendency for KCO to rise may be masked by disease-related changes in the pulmonary microvasculature.

Adult↗

Adverse effect of additional weight on exercise against gravity in patients with chronic obstructive airways disease.

The effects of an acute, artificially simulated increase in body weight on exercise performance were examined in 14 patients of normal weight (mean (SD) body mass index 22.3 (2.7)), age 61 (8) years) with chronic obstructive airways disease (FEV1 1.2 (0.5) 1; vital capacity (VC) 2.9 (0.6) 1), and in six normal subjects with similar age and sex distribution. The patients performed a six minute walking test and a symptom limited step climbing test both with and without an additional 10 kg weight (two leaded aprons). The normal subjects performed a step test with and without the additional weight. Ventilation (VE) and oxygen consumption (VO2) were measured during step climbing. Resting spirometric values were not altered by the additional weight. In the patients the median number of steps climbed fell from 67.5 when they were unweighted to 44.5 when they were weighted. Mean VE and VO2 were increased during weighted step climbing by 14% and 13% but the maximum levels of VE and VO2 achieved were similar during unweighted and weighted exercise (VE 36.8 (8.6) and 37.3 (10.2) 1 min-1, VO2 1.35 (0.3) and 1.41 (0.4) 1 min-1 respectively). The normal subjects were readily able to complete 150 steps both with and without the additional weight. In the patients the six minute walking distance fell only slightly with the extra weight, from 554 (SD 61) to 540 (62) m. A subsidiary study was carried out in six healthy younger subjects in which VE and VO2 were measured during a 5.6 km/h six minute treadmill walk at zero incline. The additional weight did not alter VE or VO2 during exercise. In conclusion, a small acute increase in body weight substantially worsened the already reduced "uphill" exercise performance in patients with chronic obstructive airways disease because of its effect on ventilation and oxygen consumption. These results suggest that modest weight loss might benefit patients with chronic obstructive airways disease even though they may be only slightly above their ideal body weight.

Body Weight↗

Effects of laser treatment on respiratory function in malignant narrowing of the central airways.

Twenty patients with inoperable carcinoma in the trachea or a main bronchus were investigated before and one and 10 days after treatment with a carbon dioxide laser. Patients were assessed by spirometry, maximum flow-volume loops, and a visual analogue score of breathlessness on a scale from 0 (not at all breathless) to 100 (very breathless). At day 10 mean FEV1 had improved from 51.9% to 62.6% of predicted (p less than 0.02) and mean peak expiratory flow (PEF) from 45.3% to 53.1% of the predicted value (p less than 0.05). Improvements in maximum inspiratory and expiratory flows at 50% vital capacity were not significant but the breathlessness score decreased from a mean of 49.1 to 35.3 (p less than 0.01). Improvements in breathlessness were significantly correlated with increases in FEV1 and PEF. Thirteen of the 20 patients had unilateral tumours with partial or complete occlusion of the main bronchus; in these perfusion and ventilation were assessed by radioisotope scans before and 10 days after treatment. Seven of the 13 patients showed an increase in perfusion of the affected lung after treatment but the improvement was small, with a mean increase in unilateral perfusion in the 13 patients of 2.4% of the total counts. Four patients with no perfusion of the affected side showed no significant improvement after laser treatment. Changes in ventilation scans were similar to those in perfusion. It is concluded that laser treatment improves airway function and dyspnoea in malignant narrowing of central airways and that in unilateral obstruction such treatment results, at best, in a small increase in the contribution of the affected lung to perfusion.

Aged↗

The effect of chest wall transcutaneous electrical nerve stimulation on dyspnoea.

We studied the effects of transcutaneous electrical nerve stimulation (TENS) over the chest wall on breathlessness in normal subjects during exercise. Eleven male subjects performed a progressive incremental exercise test to break point on four consecutive days. TENS (continuous form, frequency 100 Hz, pulse width 200 microseconds) was applied during three of these tests-over the second intercostal spaces during inspiration ('in phase' with the underlying inspiratory muscle contraction) or expiration ('out of phase' with contraction) or over the deltoid muscles during inspiration (control), and not on the fourth occasion in random order. Breathlessness (Borg scale), heart rate, respiratory frequency, tidal volume, minute ventilation and minute oxygen uptake were measured. No significant differences were found for any of the measured variables between the four study days. We conclude that TENS under these circumstances has no effect on the sensation of breathlessness or on the measured physiological variables in normal subjects during exercise.

Adult↗

The effect of intravenous metformin on glucose metabolism during hyperglycaemia in type 2 diabetes.

A stepped intravenous metformin infusion was used in conjunction with the hyperglycaemic clamp technique to study the dose-response relationship of plasma metformin concentration with hepatic glucose production and peripheral glucose disposal in nine patients with Type 2 diabetes. The study was of double-blind crossover design, using NaCl infusion as control. Plasma metformin concentrations spanning the therapeutic range (1.64 +/- 0.13 mg l-1 and 6.57 +/- 0.61 mg l-1) were achieved. No differences in peripheral glucose disposal were demonstrated when compared with NaCl infusion (3.4 +/- 0.1 vs 3.6 +/- 0.2 (+/- SE) mg kg-1 min-1 and 3.4 +/- 0.2 vs 3.3 +/- 0.2 mg kg-1 min-1, respectively). There was also no difference in basal hepatic glucose production during metformin and NaCl infusion (2.7 +/- 0.3 vs 2.8 +/- 0.2 mg kg-1 min-1). No acute effect of metformin on hepatic glucose production or peripheral glucose disposal was observed, implying that a chronic persistent effect is more important in these respects than immediate effects consequent upon changes in plasma drug level.

Blood Glucose↗

Resting energy expenditure, substrate use, and video tapes.

OBJECTIVE: To investigate the effect of watching different types of video on energy expenditure. DESIGN: Randomised study assessing a "pleasant," an "amusing," an "exciting," and no video film clips. SUBJECTS: 12 volunteers who did not know the purpose of the study. MAIN OUTCOME MEASURES: Changes in energy expenditure, substrate use, heart rate, and aural temperature during each film clip. RESULTS: Energy expenditure was raised slightly (0.21 kJ/day) during the "exciting" film. Individual responses varied greatly. CONCLUSION: Watching different types of video seems to have little effect on resting metabolic rate.

Adult↗

A neural systems analysis of adaptive navigation.

In the field of the neurobiology of learning, significant emphasis has been placed on understanding neural plasticity within a single structure (or synapse type) as it relates to a particular type of learning mediated by a particular brain area. To appreciate fully the breadth of the plasticity responsible for complex learning phenomena, it is imperative that we also examine the neural mechanisms of the behavioral instantiation of learned information, how motivational systems interact, and how past memories affect the learning process. To address this issue, we describe a model of complex learning (rodent adaptive navigation) that could be used to study dynamically interactive neural systems. Adaptive navigation depends on the efficient integration of external and internal sensory information with motivational systems to arrive at the most effective cognitive and/or behavioral strategies. We present evidence consistent with the view that during navigation: 1) the limbic thalamus and limbic cortex is primarily responsible for the integration of current and expected sensory information, 2) the hippocampal-septal-hypothalamic system provides a mechanism whereby motivational perspectives bias sensory processing, and 3) the amygdala-prefrontal-striatal circuit allows animals to evaluate the expected reinforcement consequences of context-dependent behavioral responses. Although much remains to be determined regarding the nature of the interactions among neural systems, new insights have emerged regarding the mechanisms that underlie flexible and adaptive behavioral responses.

Animals↗