Limitations to spirometry being performed in 'the office'.
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Chronic Disease↗
Biomedical subjects
B G Cooper
Publications and source records attributed to B G Cooper.
Temporary inactivation of the retrosplenial cortex causes a transient reorganization of spatial coding in the hippocampus.
The ability to navigate accurately is dependent on the integration of visual and movement-related cues. Navigation based on metrics derived from movement is referred to as path integration. Recent theories of navigation have suggested that posterior cortical areas, the retrosplenial and posterior parietal cortex, are involved in path integration during navigation. In support of this hypothesis, we have found previously that temporary inactivation of retrosplenial cortex results in dark-selective impairments on the radial maze (Cooper and Mizumori, 1999). To understand further the role of the retrosplenial cortex in navigation, we combined temporary inactivation of retrosplenial cortex with recording of complex spike cells in the hippocampus. Thus, behavioral performance during spatial memory testing could be compared with place-field responses before, and during, inactivation of retrosplenial cortex. In the first experiment, behavioral results confirmed that inactivation of retrosplenial cortex only impairs radial maze performance in darkness when animals are at asymptote levels of performance. A second experiment revealed that retrosplenial cortex inactivation impaired spatial learning during initial light training. In both experiments, the normal location of hippocampal "place fields" was changed by temporary inactivation of retrosplenial cortex, whereas other electrophysiological properties of the cells were not affected. The changes in place coding occurred in the presence, and absence, of behavioral impairments. We suggest that the retrosplenial cortex provides mnemonic spatial information for updating location codes in the hippocampus, thereby facilitating accurate path integration. In this way, the retrosplenial cortex and hippocampus may be part of an interactive neural system that mediates navigation.
Action Potentials↗
Finding your way in the dark: the retrosplenial cortex contributes to spatial memory and navigation without visual cues.
Path integration is presumed to rely on self-motion cues to identify locations in space and is subject to cumulative error. The authors tested the hypothesis that rats use memory to reduce such errors and that the retrosplenial cortex contributes to this process. Rats were trained for 1 week to hoard food in an arena after beginning a trial from a fixed starting location; probe trials were then conducted in which they began a trial from a novel place in light or darkness. After control injections, rats searched around the training location, showing normal spatial memory. Inactivation of the retrosplenial cortex disrupted this search preference. To assess accuracy during navigation, rats were then trained to perform multiple trials daily, with a fixed or a different starting location in light or darkness. Retrosplenial cortex inactivation impaired accuracy in darkness. The retrosplenial cortex may provide mnemonic information, which decreases errors when navigating in the dark.
Animals↗
Retrosplenial cortex inactivation selectively impairs navigation in darkness.
There is an emerging consensus that retrosplenial and posterior parietal cortex importantly contribute to navigation. Several theories of navigation have argued that these cortical areas, particularly retrosplenial cortex, are involved in path integration. In an effort to characterize the role of retrosplenial cortex in active navigation, the effects of temporary inactivation of retrosplenial cortex on spatial memory performance were evaluated in light and dark testing conditions. Inactivation of retrosplenial cortex selectively resulted in behavioral impairments when animals were tested in darkness. These data support the hypothesis that retrosplenial cortex contributes to navigation in darkness, perhaps by providing mnemonic associations of the visual and nonvisual environment that can be used to correct for cumulative errors that occur during path integration.
Animals↗
Hippocampal representational organization and spatial context.
The hippocampus appears to undergo continual representational reorganization as animals navigate their environments. This reorganization is postulated to be reflected spatially in terms of changes in the ensemble of place cells activated, as well as changes in place field specificity and reliability for cells recorded in both hilar/CA3 and CA1 regions. The specific contribution of the hilar/CA3 region is suggested to be to compare the expected spatial context with that currently being experienced, then relay discrepancies to CA1. The properties of CA1 place fields in part reflect the spatial comparisons made in the hilar/CA3 area. In addition, CA1 organizes the input received from the hilar/CA3 place cells according to different temporal algorithms that are unique to different tasks. In this way, hippocampus helps to distinguish temporally one spatial context from another, thereby contributing to episodic memories.
Animals↗
Evaluation of phenylalanine and tyrosine metabolism in late human pregnancy.
The [2H5]-phenylalanine method for measurement of protein metabolism requires the phenylalanine hydroxylation to tyrosine to be calculated from the tyrosine flux. Although this can be estimated, for pregnancy, we made a direct measurement of the molar ratio of the fluxes of tyrosine and phenylalanine from protein breakdown (Pt/Pp) using [2H2]-tyrosine infusion. Six normal pregnant women were studied at 37 weeks' gestation. While fasting, they were administered a 3-hour primed-constant infusion with [13C]-leucine, [2H5]-phenylalanine, and [2H2]-tyrosine. Leucine (alpha-ketoisocaproic acid [KIC]) flux was 136.2+/-15.1 micromol/kg/h (mean +/- SD), phenylalanine flux 41.2+/-5.6, and tyrosine flux 25.0+/-6.0, and phenylalanine hydroxylation was 3.3+/-2.1 micromol/kg/h. The mean tyrosine to phenylalanine molar flux ratio (Pt/Pp) was 0.52+/-0.10, lower than the ratio of 0.65 to 0.85 reported in normal nonpregnant subjects and 0.73 estimated from animal studies. We studied protein metabolism in six additional pregnant women and six nonpregnant women using [13C]-leucine and [2H5]-phenylalanine infusions only and applied the lower Pt/Pp ratio to the former group. Tyrosine flux (42.0+/-7.2 micromol/kg/h) and phenylalanine hydroxylation (9.2+/-4.2 micromol/kg/h) were significantly higher in nonpregnant subjects than in both groups of pregnant subjects. The percent contribution of phenylalanine hydroxylation to total tyrosine flux was reduced from 20% to 14%. When using [2H5]-phenylalanine to study whole-body protein metabolism in pregnancy and tyrosine flux is not measured directly by infusion of [2H2]-tyrosine, the lower Pt/Pp ratio is required. The phenylalanine model shows that tyrosine flux derived from protein breakdown and phenylalanine hydroxylation are both reduced in pregnancy.
Adult↗
Prospective audit of a respiratory sleep disorders service at District General Hospital level.
This study was designed to examine the organisation and outcomes of a District General Hospital respiratory sleep service, since data are lacking on the management of sleep-disordered breathing at this level. Questionnaires and case-notes review were used to assess the management of 119 consecutive patients referred with suspected sleep-disordered breathing. Patients diagnosed with sleep-disordered breathing were assigned nasal continuous positive airway pressure (nCPAP), ear/nose/throat (ENT) surgery or simple measures (e.g., weight loss). There were six non-attenders. At 12 months follow-up, 33 patients had been assigned to nCPAP, 25 to ENT surgery, and 37 to simple measures. Of the remainder, nine had alternative diagnoses, two were still being assessed and seven were lost to follow-up. Patients prescribed nCPAP (81% compliance) had significant symptomatic improvements with low dissatisfaction rates (20%); patients on simple measures did not improve (33% dissatisfied); only half assigned surgery had it performed, with 42% awaiting surgery and dissatisfied. Interspecialty referral resulted in major delays (mean 16 weeks). Referral letters were generally unhelpful in deciding on the appropriateness of initial referral (respiratory physician vs ENT). nCPAP was generally effective in improving symptoms, with a high level of patient satisfaction, while simple measures did not improve symptoms and were associated with lower satisfaction levels. Waiting times to ENT surgery can be long and patients express significant dissatisfaction. Referral letters are not useful in directing initial referral. Services should be co-ordinated between respiratory and ENT specialties to reduce waiting times and improve patient satisfaction.
Adult↗
Domiciliary NIPPV in COPD.
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Home Care Services↗
Superior colliculus and active navigation: role of visual and non-visual cues in controlling cellular representations of space.
To begin investigation of the contribution of the superior colliculus to unrestrained navigation, the nature of behavioral representation by individual neurons was identified as rats performed a spatial memory task. Similar to what has been observed for hippocampus, many superior collicular cells showed elevated firing as animals traversed particular locations on the maze, and also during directional movement. However, when compared to hippocampal place fields, superior collicular location fields were found to be more broad and did not exhibit mnemonic properties. Organism-centered spatial coding was illustrated by other neurons that discharged preferentially during right or left turns made by the animal on the maze, or after lateralized sensory presentation of somatosensory, visual, or auditory stimuli. Nonspatial movement-related neurons increased or decreased firing when animals engaged in specific behaviors on the maze regardless of location or direction of movement. Manipulations of the visual environment showed that many, but not all, spatial cells were dependent on visual information. The majority of movement-related cells, however, did not require visual information to establish or maintain the correlates. Several superior collicular cells fired in response to multiple maze behaviors; in some of these cases a dissociation of visual sensitivity to one component of the behavioral correlate, but not the other, could be achieved for a single cell. This suggests that multiple modalities influence the activity of single neurons in superior colliculus of behaving rats. Similarly, several sensory-related cells showed dramatic increases in firing rate during the presentation of multisensory stimuli compared to the unimodal stimuli. These data reveal for the first time how previous findings of sensory/motor representation by the superior colliculus of restrained/anesthetized animals might be manifested in freely behaving rats performing a navigational task. Furthermore, the findings of both visually dependent and visually independent spatial coding suggest that superior colliculus may be involved in sending visual information for establishing spatial representations in efferent structures and for directing spatially-guided movements.
Animals↗
Significance of solitary and multiple esophageal ulcers in patients with AIDS.
We endoscopically evaluated odynophagia and/or dysphagia in 23 patients with acquired immunodeficiency syndrome (AIDS). Eleven patients (48%) were found to have esophageal ulcers. Seven of them had deep, sharply demarcated, well-circumscribed ulcer craters with raised edges; in two the ulcer extended to the muscularis propria. Ulcers were single in four patients, multiple in six, and unspecified in one. Biopsies were nondiagnostic. In eight patients, mycobacterial, viral, and fungal cultures were negative. Specific infections diagnosed in three patients were treated with appropriate agents. Ulcers were treated symptomatically, and seven patients received therapy for suspected viral etiology. Symptoms remained unchanged in five patients, improved in three, and resolved in two. Fifty-five percent of patients died within 3.6 months (mean) of diagnosis. Large solitary and multiple esophageal ulcers are common in AIDS patients with odynophagia and dysphagia.
Acquired Immunodeficiency Syndrome↗
The effect of severe head injury on whole body energy expenditure and its possible hormonal mediators in children.
This study examines the effects of severe head injury in children on whole body energy expenditure and the mediators that influence this. One hundred five serial measurements of whole body energy expenditure and plasma adrenaline, triiodothyronine, glucagon, cortisol, insulin, and growth hormone concentrations were made in 18 children aged 2-15 y receiving neurointensive care for severe head injury. Energy expenditure was measured using indirect calorimetry by a modified Douglas bag technique, and hormones were measured by RIA or radioenzymatic assay. Energy expenditure varied markedly between and within children (mean 97% of predicted, range 60-137%) and was significantly lower in the four children with a poor outcome (p = 0.03). Within each child there were statistically significant positive relationships between energy expenditure and adrenaline (p < 0.0001), triiodothyronine (p < 0.0001), and glucagon (p < 0.0001). However, there was evidence that the effect of adrenaline on energy expenditure was attenuated. This may be due to the effects of the cerebral trauma itself on central nervous influences on energy expenditure, to interactions between hormones, or to a global impairment of O2 utilization by the body's tissues.
Adolescent↗
Hormonal and metabolic profiles in subjects with obstructive sleep apnea syndrome and the acute effects of nasal continuous positive airway pressure (CPAP) treatment.
Nocturnal secretion of growth hormone is impaired in patients with obstructive sleep apnea (OSA), but the metabolic consequences have not been reported. We measured blood levels of the hormones insulin, C-peptide, growth hormone, cortisol and glucagon together with the intermediary metabolites of carbohydrate (glucose, pyruvate, lactate, alanine) and lipid metabolism [glycerol, nonesterified fatty acids (NEFA), 3-hydroxybutyrate] in six obese nondiabetic men with OSA on two nights. In the first study, the untreated subjects showed frequent apneas and consequent hypoxemia. The hormone and metabolite concentrations were compared with those obtained on the following night when the subjects were treated effectively with nasal continuous positive airway pressure (CPAP). There were no significant differences in the concentrations of insulin, C-peptide, cortisol or glucagon. We confirmed a marked reduction in growth hormone concentrations in OSA, with a significant increase on the CPAP night. The nocturnal profiles of glucose, pyruvate, lactate, alanine and glycerol showed no differences between the two nights, but concentrations of NEFA and 3-hydroxybutyrate, both products of lipolysis, were significantly greater on the treatment night. Because growth hormone has a lipolytic action, the results suggest that suppression of secretion of growth hormone in untreated OSA results in impaired lipolysis, which is rapidly reversed by nasal CPAP.
Adult↗
Breathing pattern awake and asleep in patients with myotonic dystrophy.
Patients with myotonic dystrophy often have an irregular pattern of breathing at rest, implying abnormality of breathing control. No central medullary defect has been found in such patients. We postulated that irregular breathing in myotonic dystrophy due to abnormal central respiratory output would persist during slow-wave sleep. We examined the patterns of breathing whilst awake and asleep in seven patients with myotonic dystrophy, seven similarly weak nonmyotonic subjects and seven normal controls. Polysomnography was performed, and the coefficients of variation (CoV) of the breath intervals were analysed during different stages of sleep. The myotonic group showed significantly greater variation in breath intervals than the other two groups whilst awake (median CoV 37 vs 18% for nonmyotonics) and during light sleep (31 vs 13%). This difference was not evident during slow-wave sleep (median CoV 12 vs 9% in nonmyotonic). We conclude that irregular breathing in patients with myotonic dystrophy whilst awake and during light sleep, does not persist during slow-wave sleep. These results suggest that "behavioural" influences play a role in the abnormal breathing pattern found in myotonic dystrophy. The source of the irregular breathing is unlikely to be found in the medulla, but may originate from forebrain influences.
Adult↗
The effect of controlled-release salbutamol on sleep and nocturnal oxygenation in patients with asthma and chronic obstructive pulmonary disease.
Patients with asthma or chronic obstructive pulmonary disease (COPD) may have falls in oxygen saturation at night. We have investigated the effect of a long acting beta agonist (salbutamol CR) on nocturnal oxygen saturation (SaO2) in asthma and COPD. Eleven asthmatic and 14 COPD patients in stable condition were randomly allocated to 8 mg salbutamol CR or placebo twice daily in a double-blind, cross-over study. FEV1 at entry was 71.5% predicted in the asthmatic patients and 36% predicted in the COPD group. Each treatment period lasted 7 days, at the end of which measurements of ventilatory function and detailed sleep studies were performed. There was a significant improvement in morning FEV1 in the asthmatic patients when on active treatment and a small, but non-significant improvement in the COPD group. Sleep architecture and oxygenation were similar on placebo and on active treatment in both groups. We conclude that salbutamol CR has no significant effect on nocturnal oxygenation or sleep pattern in patients with mild asthma or moderately severe COPD.
Albuterol↗
Recovery of 13C in breath from infused NaH13CO3 increases during euglycaemic hyperinsulinaemia.
1. The effect of euglycaemic hyperinsulinaemia on the recovery of 13C in expired CO2 has been assessed in six normal subjects. Each was studied on three occasions: once with a 6 h primed constant infusion of NaH13CO3 combined with a euglycaemic hyperinsulinaemic clamp for the last 3 h (study 1), once with a 6 h primed constant infusion of NaH13CO3 alone (study 2) and once with a 6 h infusion of normal saline combined with a hyperinsulinaemic clamp for the last 3 h (study 3). Measurements of 13C enrichment of expired CO2 were made in the third and sixth hour of each infusion. 2. There was no significant increase in enrichment during study 3 (3 h 0.00047 +/- 0.00016 versus 6 h 0.00069 +/- 0.00028 atom per cent excess) with potato-starch-derived D-glucose used to maintain euglycaemia. 13C recovery increased in the sixth hour of both study 1 and 2 (study 1: 3 h 74.4 +/- 2.0 versus 6 h 85.5 +/- 2.6%, P < 0.01; study 2: 3 h 72.1 +/- 2.4 versus 6 h 81.7 +/- 1.4%, P < 0.01). There was no significant difference in recovery between studies 1 and 2. 3. These results suggest that increased recovery during a sequential euglycaemic clamp is predominantly time-dependent. Studies which use this technique to examine the effect of insulin on substrate oxidation should take this into account.
Adult↗
The impact of metformin therapy on hepatic glucose production and skeletal muscle glycogen synthase activity in overweight type II diabetic patients.
The effect of metformin therapy on glucose metabolism was examined in eight overweight newly presenting untreated type II diabetic patients (five males, three females). Patients were treated for 12 weeks with either metformin (850 mg x 3) or matching placebo using a double-blind crossover study design; patients were studied at presentation and at the end of each treatment period. Insulin action was assessed by measuring activation of skeletal muscle glycogen synthase (GS) before and during a 4-hour hyperinsulinemic euglycemic clamp (100 mU.kg-1 x h-1). Metformin therapy was associated with a significant decrease in fasting blood glucose (6.8 +/- 0.6 v 8.3 +/- 0.9 mmol.L-1, P < .01) and glycosylated hemoglobin ([HbA1] 7.7% +/- 0.4% v 8.5% +/- 0.5%, P < .01) levels. Fasting hepatic glucose production (HGP) was also significantly decreased following metformin therapy (1.98 +/- 0.13 v 2.41 +/- 0.20 mg.kg-1 x min-1, P < .02), whereas fasting insulin and C-peptide concentrations remained unaltered. The decrease in basal HGP correlated closely with the decrease in fasting blood glucose concentration (r = .92, P < .001). Insulin-stimulated glucose uptake was assessed using the hyperinsulinemic euglycemic clamp technique and was increased post-metformin (3.8 +/- 0.6 v 3.1 +/- 0.7 mg.kg-1 x min-1, P < .05). This was primarily the result of increased nonoxidative glucose metabolism (1.1 +/- 0.6 v 0.4 +/- 0.6 mg.kg-1 x min-1, P < .05); oxidative glucose metabolism did not change. Metformin had no measurable effect on insulin activation of skeletal muscle GS, the rate-limiting enzyme controlling muscle glucose storage.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The role of plasma non-esterified fatty acids during exercise in type 2 diabetes mellitus.
Elevated fasting plasma non-esterified fatty acid (NEFA) levels have been reported in Type 2 diabetes. We examined whether such changes persist during low-grade exercise and influence carbohydrate metabolism. Eight Type 2 diabetic patients with moderate glycaemic control and eight healthy controls received the anti-lipolytic agent, acipimox, or placebo on separate occasions before exercising for 45 min at 35% pre-determined VO2max. Fasting plasma NEFA levels were similar (0.40 +/- 0.06 (SEM) and 0.45 +/- 0.05 mmol l-1; healthy and Type 2 diabetic subjects) following placebo, and increased to comparable levels with exercise (0.73 +/- 0.07 and 0.73 +/- 0.10 mmol l-1). Acipimox lowered basal NEFA levels (0.14 +/- 0.03 and 0.28 +/- 0.04 mmol l-1; both p < 0.05 vs placebo), and prevented the rise with exercise. Blood glucose (p < 0.001) and serum insulin (p < 0.01) levels were higher in the Type 2 diabetic patients (vs controls) for both treatments. Whole body lipid oxidation increased from baseline to a comparable degree with exercise following placebo (3.2 +/- 0.3 and 2.8 +/- 0.3 mg kg-1 min-1; healthy and Type 2 diabetic subjects, both p < 0.02). Although less marked, the same was also observed following acipimox (2.0 +/- 0.4 and 2.1 +/- 0.5 mg kg-1 min-1; both p < 0.05). Carbohydrate oxidation increased with exercise in both subject groups, but with no significant difference between the treatments. Thus, the metabolic response to low-grade exercise was normal in Type 2 diabetic patients with moderate glycaemic control, but occurred against a background of hyperinsulinaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
3-Hydroxybutyric Acid↗
Do nonesterified fatty acids regulate skeletal muscle protein turnover in humans?
We examined whether elevated plasma nonesterified fatty acid (NEFA) levels exert a direct effect on protein metabolism by measuring [2H5]phenylalanine skeletal muscle exchange and whole body turnover. [2H5]phenylalanine was infused (0.5 mg.kg-1 x h-1) for 300 min in seven healthy subjects on two occasions. Intralipid (10%; 30 ml/h) or 0.154 mol/l NaCl was infused in random order from 120 min. Measurements were taken during basal (90-120 min) and infusion (270-300 min) periods. Intralipid infusion increased plasma NEFA levels [1.31 +/- 0.13 vs. 0.49 +/- 0.05 (SE) mmol/l; P < 0.05] and forearm NEFA uptake [45 +/- 76 vs. -51 +/- 44 nmol . 100 ml forearm-1 x min-1; P < 0.05]. Serum insulin and blood ketone body levels were similar with the two treatments. Elevated plasma NEFA levels were associated with a comparable decrease in forearm phenylalanine uptake (11 +/- 2 vs. 17 +/- 2 nmol x 100 ml forearm-1 x min-1; lipid vs. control, P < 0.05) and release (20 +/- 2 vs. 26 +/- 3 nmol x 100 ml forearm-1 x min-1; lipid vs. control, P < 0.05). However, there were no significant changes in net forearm phenylalanine exchange and whole body phenylalanine turnover. Therefore, elevated plasma NEFA levels were associated with a comparable decrease in the rates of skeletal muscle protein synthesis and breakdown but did not appear to influence overall protein balance, as assessed using [2H5]phenylalanine.
Adult↗