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Biomedical subjects

D G Thompson

Publications and source records attributed to D G Thompson.

At least 19 recordsLinked to original sources
PubMed2006

Deglutitive laryngeal closure in stroke patients.

BACKGROUND: Dysphagia has been reported in up to 70% of patients with stroke, predisposing them to aspiration and pneumonia. Despite this, the mechanism for aspiration remains unclear. AIMS: To determine the relationship between bolus flow and laryngeal closure during swallowing in patients with stroke and to examine the sensorimotor mechanisms leading to aspiration. METHODS: Measures of swallowing and bolus flow were taken from digital videofluoroscopic images in 90 patients with stroke and 50 healthy adults, after repeated volitional swallows of controlled volumes of thin liquid. Aspiration was assessed using a validated Penetration-Aspiration Scale. Oral sensation was also measured by electrical stimulation at the faucial pillars. RESULTS: After stroke, laryngeal ascent was delayed (mean (standard deviation (SD)) 0.31 (0.06) s, p<0.001), resulting in prolongation of pharyngeal transit time (1.17 (0.07) s, p<0.001) without a concomitant increase in laryngeal closure duration (0.84 (0.04) s, p = 0.9). The delay in laryngeal elevation correlated with both the severity of aspiration (r = 0.5, p<0.001) and oral sensation (r = 0.5, p<0.001). CONCLUSIONS: After stroke, duration of laryngeal delay and degree of sensory deficit are associated with the severity of aspiration. These findings indicate a role for sensorimotor interactions in control of swallowing and have implications for the assessment and management of dysphagia after stroke.

Adult↗
PubMed2006

Neurophysiological evaluation of healthy human anorectal sensation.

Patients with functional gastrointestinal disorders often demonstrate abnormal visceral sensation. Currently, rectal sensation is assessed by manual balloon distension or barostat. However, neither test is adaptable for use in the neurophysiological characterization of visceral afferent pathways by sensory evoked potentials. The aim of this study was to assess the reproducibility and quality of sensation evoked by electrical stimulation (ES) and rapid balloon distension (RBD) in the anorectum and to apply the optimum stimulus to examine the visceral afferent pathway with rectal evoked potentials. Healthy subjects (n = 8, median age 33 yr) were studied on three separate occasions. Variability, tolerance, and stimulus characteristics were assessed with each technique. Overall ES consistently invoked pain and was chosen for measuring rectal evoked potential whereas RBD in all cases induced the strong urge to defecate. Rectal intraclass correlation coefficient (ICC) for ES and RBD (0.82 and 0.72, respectively) demonstrated good reproducibility at pain/maximum tolerated volume but not at sensory threshold. Only sphincter ICC for ES at pain showed acceptable between-study reproducibility (ICC 0.79). Within studies ICC was good (>0.6) for anorectal ES and RBD at both levels of sensation. All subjects reported significantly more unpleasantness during RBD than ES (P < 0.01). This study demonstrates that ES and RBD are similarly reproducible. However, the sensations experienced with each technique differed markedly, probably reflecting differences in peripheral and/or central processing of the sensory input. This is of relevance in interpreting findings of neuroimaging studies of anorectal sensation and may provide insight into the physiological characteristics of visceral afferent pathways in health and disease.

Adolescent↗
PubMed2006

Perceptual wind-up in the human oesophagus is enhanced by central sensitisation.

BACKGROUND: Oesophageal acid infusion induces enhanced pain hypersensitivity in non-acid exposed upper oesophagus (secondary hyperalgesia) in patients with non-cardiac chest pain, thus suggesting central sensitisation contributes to visceral pain hypersensitivity in functional gut disorders (FGD). Perceptual wind-up (increased pain perception to constant intensity sensory stimuli at frequencies>or=0.3 Hz) is used as a proxy for central sensitisation to investigate pain syndromes where pain hypersensitivity is important (for example, fibromyalgia). AIMS: Wind-up in central sensitisation induced human visceral pain hypersensitivity has not been explored. We hypothesised that if wind-up is a proxy for central sensitisation induced human visceral pain hypersensitivity, then oesophageal wind-up should be enhanced by secondary hyperalgesia. METHODS: In eight healthy volunteers (seven males; mean age 32 years), perception at pain threshold to a train of 20 electrical stimuli applied to the hand and upper oesophagus (UO) at either 0.1 Hz (control) or 2 Hz was determined before and one hour after a 30 minute lower oesophageal acid infusion. RESULTS: Wind-up occurred only with the 2 Hz train in the UO and hand (both p=0.01). Following acid infusion, pain threshold decreased (17 (4)%; p=0.01) in the UO, suggesting the presence of secondary hyperalgesia. Wind-up to the 2 Hz train increased in the UO (wind-up ratio 1.4 (0.1) to 1.6 (0.1); p=0.03) but not in the hand (wind-up ratio 1.3 (0.1) and 1.3 (0.1); p=0.3) CONCLUSION: Enhanced wind-up after secondary oesophageal hyperalgesia suggests that visceral pain hypersensitivity induced by central sensitisation results from increased central neuronal excitability. Wind-up may offer new opportunities to investigate the contribution of central neuronal changes to symptoms in FGD.

Adult↗
PubMed2006

Assessing the temporal reproducibility of human esophageal motor-evoked potentials to transcranial magnetic stimulation.

BACKGROUND: Although the electrophysiological properties and reproducibility of somatic limb motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) are well characterized, little is known about the reproducibility of MEPs for viscerosomatic structures such as the esophagus. AIM: To determine the temporal reproducibility of esophageal MEPs to TMS. METHODS: MEPs to TMS were recorded from the proximal esophagus, using a swallowed catheter housing a pair of electrodes, in eight healthy subjects at five stimulus intensities (SI) (motor threshold [MT] to 20% above MT). For each SI, 20 consecutive TMS stimuli at 5-second intervals were delivered over a single scalp site (dominant hemisphere at site exhibiting MT at lowest SI) and repeated 40 and 80 minutes thereafter. MEP amplitudes and latencies were measured, and means were sequentially calculated for each SI and then log-transformed. The repeatability coefficients (RC) for the three time points were calculated across each set of 20 stimuli and presented as an exponential ratio. RESULTS: Best RC (amplitude/latency) were achieved at 120% SI relative to MT, being 1.8/1.2 (optimal = 1.0). For lower intensities of 115%, 110%, 105%, and 100% SI, the RC were 2.1/1.2, 2.1/1.1, 2.4/1.2, and 2.6/1.4, respectively. For all SI, the greatest reductions in RC occurred over the first 10 stimuli, with little additional gain beyond this number. CONCLUSIONS: Latencies of esophageal MEP to TMS across intensities are highly reproducible, whereas amplitudes are more stimulus intensity-dependent, being most reliable and reproducible at the highest stimulus strengths. SIGNIFICANCE: Using careful parameters, TMS can be used reliably in future studies of viscerosomatic structures, although the size of the response variability needs to be taken into account when assessing changes in cortico-fugal activity.

Adult↗
PubMed2005

Feeding-dependent depression of melanin-concentrating hormone and melanin-concentrating hormone receptor-1 expression in vagal afferent neurones.

Food intake is regulated by signals from the gastrointestinal tract. Both stimulation and inhibition of food intake may be mediated by upper gastrointestinal tract hormones, e.g. ghrelin and cholecystokinin that act at least partly via vagal afferent neurones. We now report that vagal afferent neurones in both rat and man express melanin-concentrating hormone and its receptor, melanin-concentrating hormone-1R. In nodose ganglia from rats fasted for 24 h, RT-PCR revealed the expression of both melanin-concentrating hormone and melanin-concentrating hormone-1R, whereas in ganglia from animals fed ad libitum expression was virtually undetectable. Immunohistochemical studies also revealed expression of melanin-concentrating hormone and melanin-concentrating hormone-1R in nodose ganglion neurones of fasted rats, but signals were weak in rats fed ad libitum. Melanin-concentrating hormone and melanin-concentrating hormone-1R were expressed in the same neurones, a high proportion of which also expressed the cholecystokinin-1 receptor. When fasted rats were refed, there was down-regulation of melanin-concentrating hormone and melanin-concentrating hormone-1R expression over a period of 5 h. Similar effects were produced by administration of cholecystokinin to fasted rats. The cholecystokinin-1 receptor antagonist lorglumide inhibited food-induced down-regulation of melanin-concentrating hormone and melanin-concentrating hormone-1R. We conclude that the satiety hormone cholecystokinin acts on vagal afferent neurones to inhibit expression of melanin-concentrating hormone and its receptor. Since the melanin-concentrating hormone system is associated with stimulation of food intake this effect of cholecystokinin may contribute to its action as a satiety hormone.

Afferent Pathways↗
PubMed2005

Immune control of food intake: enteroendocrine cells are regulated by CD4+ T lymphocytes during small intestinal inflammation.

BACKGROUND AND AIMS: Gastrointestinal inflammation reduces food intake but the biological mechanisms explaining suppressed feeding during inflammation are unknown. We have used a model of upper gut infection (Trichinella spiralis in the mouse) to study the effect of inflammation on food intake, and explored the role of a key enteroendocrine cell (EEC) in the regulation of feeding by the immune response. METHODS: Food intake of NIH mice infected with the intestinal nematode Trichinella spiralis was measured. Duodenal cholecystokinin (CCK) cells were counted. Plasma CCK was measured. Infected mice were treated with a specific CCK1 receptor antagonist, and food intake reassessed. The influence of the immune response on food intake and CCK was mechanistically examined by treating mice with CD4 or mast cell neutralising antibodies. The role of the T helper 2 response was further explored in mice genetically deficient for interleukin (IL)-4, IL-13, or IL-4Ralpha (receptor alpha subunit). RESULTS: Food intake of infected mice was significantly reduced at the temporal peak of intestinal inflammation. CCK expressing EEC were upregulated in infected mice, and plasma CCK levels were increased. A CCK1 receptor antagonist restored the food intake of infected mice to a significant degree. Furthermore, suppression of food intake was completely abolished in the absence of CD4+ T lymphocytes or IL-4Ralpha. CONCLUSIONS: The data show for the first time that intestinal inflammation results in reduced food intake due to upregulation of CCK. Moreover, following infection, food intake and CCK expressing cells are under the specific control of CD4+ T-cells, via release of IL-4 and IL-13.

Animals↗
PubMed2005

A randomised controlled trial of self-help interventions in patients with a primary care diagnosis of irritable bowel syndrome.

INTRODUCTION: Functional abdominal symptoms are very common and account for nearly two million primary care consultations in Britain every year and produce significant morbidity. The aims of this study were to evaluate the impact of two self-help interventions on consultation rates and symptom severity in patients with a primary care diagnosis of irritable bowel syndrome. METHODS: A total of 420 patients from 54 primary care centres were randomised either to receive self-help information in the form of a guidebook or the guidebook plus a "self-help" group meeting or to be in a control group receiving neither intervention. Data were collected using questionnaires and primary care records. RESULTS: At one year, patients in the guidebook group had a 60% reduction in primary care consultations (p < 0.001) and a reduction in perceived symptom severity (p < 0.001) compared with controls. Allocation to the self-help group conferred no additional benefit. Actual symptom scores did not change significantly in any group. Costs per patient were reduced by Pounds 73 (confidence interval Pounds 43, Pounds 103) or 40% per year. CONCLUSION: Introduction of a self-help guidebook results in a reduction in primary care consultations, a perceived reduction in symptoms, and significant health service savings. This suggests that patients attending their primary care physician with functional abdominal symptoms should be offered self-help information as part of their management.

Adult↗
PubMed2004

Fate and effects of azadirachtin in aquatic mesocosms--1: fate in water and bottom sediments.

The fate and effects of azadirachtin were examined using in situ enclosures deployed in a typical forest pond of northern Ontario. A commercial azadirachtin-based insecticide formulation, Neemix 4.5, was applied as the test substance. Fate studies were conducted to determine kinetics and persistence of azadirachtin isomers A and B in the aqueous phase and whether either isomer partitioned significantly to bottom sediments or pore water. Aqueous azadirachtin residues dissipated following slow linear kinetics with time to 50% dissipation of 25, 45, and 30 days for azadirachtin A, azadirachtin B, and total residues, respectively. Sediment pore water concentrations increased slowly, reaching low-level equilibrium with the overlying water column toward the end of the summer season. No significant sorption to bottom sediments was observed. Results demonstrated that fate and dissipation of azadirachtin residues are consistent from year to year and that biota may be chronically exposed to diminishing levels of azadirachtins A and B in aqueous phase under conditions of a typical forest pond environment.

Analysis of Variance↗
PubMed2004

Dissociating the spatio-temporal characteristics of cortical neuronal activity associated with human volitional swallowing in the healthy adult brain.

Human swallowing represents a complex highly coordinated sensorimotor function whose functional neuroanatomy remains incompletely understood. Specifically, previous studies have failed to delineate the temporo-spatial sequence of those cerebral loci active during the differing phases of swallowing. We therefore sought to define the temporal characteristics of cortical activity associated with human swallowing behaviour using a novel application of magnetoencephalography (MEG). In healthy volunteers (n = 8, aged 28-45), 151-channel whole cortex MEG was recorded during the conditions of oral water infusion, volitional wet swallowing (5 ml bolus), tongue thrust or rest. Each condition lasted for 5 s and was repeated 20 times. Synthetic aperture magnetometry (SAM) analysis was performed on each active epoch and compared to rest. Temporal sequencing of brain activations utilised time-frequency wavelet plots of regions selected using virtual electrodes. Following SAM analysis, water infusion preferentially activated the caudolateral sensorimotor cortex, whereas during volitional swallowing and tongue movement, the superior sensorimotor cortex was more strongly active. Time-frequency wavelet analysis indicated that sensory input from the tongue simultaneously activated caudolateral sensorimotor and primary gustatory cortex, which appeared to prime the superior sensory and motor cortical areas, involved in the volitional phase of swallowing. Our data support the existence of a temporal synchrony across the whole cortical swallowing network, with sensory input from the tongue being critical. Thus, the ability to non-invasively image this network, with intra-individual and high temporal resolution, provides new insights into the brain processing of human swallowing.

Adult↗
PubMed2004

A randomised controlled trial to assess the effectiveness and cost of a patient orientated self management approach to chronic inflammatory bowel disease.

OBJECTIVES: We developed a patient centred approach to chronic disease self management by providing information designed to promote patient choice. We then conducted a randomised controlled trial of the approach in inflammatory bowel disease (IBD) to assess whether it could alter clinical outcome and affect health service use. DESIGN: A multicentre cluster randomised controlled trial. SETTING: The trial was conducted in the outpatient departments of 19 hospitals with randomisation by treatment centre, 10 control sites, and nine intervention sites. For patients at intervention sites, an individual self management plan was negotiated and written information provided. PARTICIPANTS: A total of 700 patients with established inflammatory bowel disease were recruited. MAIN OUTCOME MEASURES: Main outcome measures recorded at one year were: quality of life, health service resource use, and patient satisfaction. Secondary outcomes included measures of enablement-confidence to cope with the condition. RESULTS: One year following the intervention, self managing patients had made fewer hospital visits (difference -1.04 (95% confidence interval (CI) -1.43 to -0.65); p<0.001) without increase in the number of primary care visits, and quality of life was maintained without evidence of anxiety about the programme. The two groups were similar with respect to satisfaction with consultations. Immediately after the initial consultation, those who had undergone self management training reported greater confidence in being able to cope with their condition (difference 0.90 (95% CI 0.12-1.68); p<0.03). CONCLUSIONS: Adoption of this approach for the management of chronic disease such as IBD in the NHS and other managed health care organisations would considerably reduce health provision costs and benefit disease control.

Adaptation, Psychological↗
PubMed2003

Calcium mobilisation and CCK secretion induced by modified fatty acids and latex microspheres reveal dual receptor mechanisms for lipid stimulation of STC-1 cells.

How fatty acids stimulate enteroendocrine cells to release cholecystokinin (CCK) is largely unknown. Recently, we proposed that the murine enteroendocrine cell line, STC-1, responds to insoluble fatty acid aggregates rather than fatty acid monomers in solution. This hypothesis led to two testable predictions. First, other insoluble particles of similar size but unrelated to fatty acid may be able to stimulate STC-1 cells in a similar fashion to dodecanoic acid and second, fatty acid sensing in STC-1 cells should be fairly insensitive to chemical modifications of the fatty acid as long as these modifications do not greatly alter the ability of the molecule to form insoluble aggregates. We used several analogues of dodecanoic acid and several varieties of latex microsphere (varying in size and surface charge) to see whether the predictions of our model hold. We found that while there was at least one latex microsphere that could induce CCK secretion and calcium mobilisation in STC-1 cells, there was a very poor correlation between the presence of insoluble aggregates and a cellular response. Instead the most important property, determining the potency of fatty acid analogues as stimulants of CCK secretion, was their amphipathicity. Removal of either the polar head or lipophilic tail completely abolished the ability of a given fatty acid analogue to stimulate STC-1 cells. These data suggested that while fatty acids can stimulate cells as aggregates, they may also be acting in monomeric form with the oil:water partitioning coefficient playing a crucial role. We finally resolved this issue with the observation that the sulfate ion greatly altered the response of STC-1 cells to monomeric dodecanoic acid. In the presence of sulfate, STC-1 cells will only respond to dodecanoic acid aggregates whereas when sulfate is replaced with chloride the cells clearly respond to dodecanoic acid monomers which are completely in solution. In summary, we propose that dodecanoic acid can stimulate STC-1 cells via two separate pathways one involving fatty acid monomers in solution and one involving fatty acid aggregates. Which pathway dominates depends on the presence of sulfate in the extracellular medium.

Animals↗
PubMed2003

Changes in pharyngeal corticobulbar excitability and swallowing behavior after oral stimulation.

Faucial pillar (FP) stimulation is commonly used in swallowing rehabilitation, yet its physiological basis remains uncertain. We investigated the effects of intraoral FP stimulation on human corticobulbar excitability and swallowing behavior, to explore the possibility of a central mechanism for functional change. In 10 healthy subjects, corticobulbar projections to pharynx were investigated with transcranial magnetic stimulation, via intraluminal electrodes, before and up to 1 h after 10 min of electrical FP stimulation with three frequencies (0.2, 1, and 5 Hz) or sham and peripheral (median nerve) stimulation. In a second study, swallowing behavior was assessed with videofluoroscopy before and after FP stimulation. FP stimulation at 5 Hz inhibited the corticobulbar projection (-14 +/- 6%, P < 0.02) and lengthened swallow response time (+114 +/- 24%, P = 0.02). By comparison, FP stimulation at 0.2 Hz facilitated this projection (+60 +/- 28%, P < 0.04), without enhancing swallowing behavior. Neither 1-Hz, sham, nor median nerve stimulation altered excitability. Thus changes in corticobulbar excitability to FP stimulation are frequency dependent with implications for the treatment for neurogenic swallowing dysfunction.

Adult↗
PubMed2003

Cognitive modulation of the cerebral processing of human oesophageal sensation using functional magnetic resonance imaging.

BACKGROUND: While cortical processing of visceral sensation has been described, the role that cognitive factors play in modulating this processing remains unclear. AIM: To investigate how selective and divided attention modulate the cerebral processing of oesophageal sensation. METHODS: In seven healthy volunteers (six males, mean age 33 years; ranging from 24 to 41 years old) from the general community, phasic visual and oesophageal (non-painful balloon distension) stimuli were presented simultaneously. During the selective attention task, subjects were instructed to press a button either to a change in frequency of oesophageal or visual stimuli. During a divided attention task, subjects received simultaneous visual and oesophageal stimuli and were instructed to press a button in response to a change in frequency of both stimuli. RESULTS: Selectively focussing attention on oesophageal stimuli activated the visceral sensory and cognitive neural networks (primary and secondary sensory cortices and anterior cingulate cortex respectively) while selective attention to visual stimuli primarily activated the visual cortex. When attention was divided between the two sensory modalities, more brain regions in the sensory and cognitive domains were utilised to process oesophageal stimuli in comparison to those employed to process visual stimuli (p=0.003). CONCLUSION: Selective and divided attention to visceral stimuli recruits more neural resources in both the sensory and cognitive domains than attention to visual stimuli. We provide neurobiological evidence that demonstrates the biological importance placed on visceral sensations and demonstrate the influence of cognitive factors such as attention on the cerebral processing of visceral sensation.

Adult↗
PubMed2002

Fatty acid signalling in a mouse enteroendocrine cell line involves fatty acid aggregates rather than free fatty acids.

Fatty acids induce cholecystokinin (CCK) secretion both in humans and from murine enteroendocrine cell lines. In both cases, only fatty acids above a critical acyl chain length (C(10)) are capable of inducing a response. Using the enteroendocrine cell line STC-1, the aim of this study was to determine whether this acyl chain length dependency is related to the fact that longer chain fatty acids are relatively insoluble in aqueous solutions and, if so, whether it is insoluble aggregates of fatty acids rather than free fatty acids which evoke CCK secretion. Solutions of fatty acids (chain length C(8)-C(14)), which were judged by filtration and Zeta sizer measurement to contain no fatty acid aggregates, never evoked CCK secretion from STC-1 cells. Filtering fatty acid solutions (of chain length C(10), C(12) and C(14)) through polytetrafluoroethylene (PTFE) filters (0.45 microm pore size) revealed a narrow concentration range for each acid over which the amount of fatty acid removed from the solution increased sharply due to the formation of fatty acid aggregates. Filtration experiments, in which suspensions of C(10), C(12) and C(14) fatty acids were passed through pore sizes of 0.2, 0.45 or 1.2 microm, suggested that STC-1 cells did not respond to fatty acid aggregates of greater than 1.2 microm, while at least 50 % of the CCK response was mediated by aggregates which were smaller than 0.45 microm. Fatty acids induce CCK secretion from STC-1 cells by elevating intracellular Ca(2+) concentration ([Ca(2+)](i)). We therefore measured the effects on [Ca(2+)](i) of filtered C(10), C(12) and C(14) fatty acids. In all cases, [Ca(2+)](i) responses were closely correlated with CCK secretion. Interestingly, while filtrates of fatty acid solutions evoked CCK secretion and elevated [Ca(2+)](i), freshly prepared solutions of fatty acids at the same concentration as the filtrates did not. This suggested that fatty acid aggregates were not in equilibrium with the solvent after filtration. The observation that the ability of C(10), C(12) and C(14) filtrates to elevate [Ca(2+)](i) decayed with time was consistent with this hypothesis. Furthermore, sonication of the filtrates abolished their ability to elevate [Ca(2+)](i). These data further suggest that it is a physical property of the fatty acid solution (the presence of insoluble fatty aggregates) which is responsible for the observed cellular responses. We conclude that Ca(2+) mobilisation and CCK secretion in STC-1 cells is driven by a signal transduction mechanism that senses insoluble fatty acid aggregates, rather than free fatty acids in solution.

Animals↗
PubMed2002

Expression of the leptin receptor in rat and human nodose ganglion neurones.

There is evidence for interactions between leptin and cholecystokinin in controlling food intake. Since cholecystokinin acts on vagal afferent neurones, we asked whether the leptin receptor was also expressed by these neurones. Primers for different forms of the leptin receptor were used in reverse transcriptase-polymerase chain reaction (RT-PCR) of rat and human nodose ganglia. RT-PCR yielded products corresponding to the long (functional) form as well as short forms of the rat leptin receptor. Moreover, RT-PCR revealed the long form of the leptin receptor in a human nodose ganglion. The identities of RT-PCR products were confirmed by sequencing. Primers corresponding to leptin itself did not give RT-PCR products in nodose ganglia. Immunocytochemical studies revealed leptin-receptor immunoreactivity in neuronal cell bodies. Many neurones co-expressed the leptin and cholecystokinin type A receptors, or leptin receptor and cocaine- and amphetamine-related transcript. We conclude that vagal afferent neurones that express the cholecystokinin type A receptor and cocaine- and amphetamine-related transcript, may also express the long form of the leptin receptor providing a neurochemical basis for observations of interactions between cholecystokinin and leptin.

Animals↗
PubMed2002

Identification of the biomechanical factors associated with the perception of distension in the human esophagus.

Current techniques used to investigate the mechanisms responsible for the sensory responses to distension of the human esophagus provide limited information because the degree of circumferential stretch required to determine tension can only be inferred. We used impedance planimetry to measure the cross-sectional area during esophageal distension to ascertain the degree of stretch and tension that initiated motor and sensory responses. Hyoscine-N-butyl bromide (HBB), a cholinergic muscarinic receptor blocker, was also used to alter esophageal tension during distension. Motor activity was initiated at a lower degree of stretch and tension than that which initiated sensory awareness; both increased directly with increasing distension. HBB reduced both esophageal motility and tension during distension without altering the relationship between sensation intensity and cross-sectional area. Esophageal stretch, rather than tension, thus appears to be the major factor influencing sensory responses to esophageal distension.

Adolescent↗