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Biomedical subjects

D G Thompson

Publications and source records attributed to D G Thompson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Guided self-management and patient-directed follow-up of ulcerative colitis: a randomised trial.

BACKGROUND: Ulcerative colitis is managed mainly in secondary care by regular outpatient reviews done by specialist clinicians. Alternatives would be to discharge patients to primary care or to provide open-access clinics, but neither of these options reduce patients' dependency on doctors or allow patients' involvement in disease management. We did a randomised controlled trial to assess an alternative to traditional outpatient care. METHODS: We randomly assigned 203 patients with ulcerative colitis who were undergoing hospital follow-up to receive patient-centred self-management training and follow-up on request (intervention group), or normal treatment and follow-up (control group). The main outcome was the interval between relapse and treatment, and secondary outcomes were rates of primary and secondary care consultation, quality of life, and acceptability to patients. Analysis was by intention to treat. FINDINGS: Intervention patients had relapses treated within a mean of 14.8 h (SD 19.1) compared with 49.6 h (65.1) in controls (difference 34.8 h [95% CI 16.4-60.2]). Furthermore, intervention patients compared with controls made significantly fewer visits to hospital (0.9 vs 2.9 per patient per year, difference 2.0 [1.6-2.7]) and to the primary-care physician (0.3 vs 0.9 per patient per year, difference 0.6 [0.2-1.1], p<0.006). Only two patients in the intervention group preferred traditional management. Health-related quality-of-life scores were unchanged in both groups. INTERPRETATION: Self-management of ulcerative colitis accelerates treatment provision and reduces doctor visits, and does not increase morbidity. This approach could be used in long-term management of many other chronic diseases to improve health-service provision and use, and to reduce costs.

Administration, Topical↗
PubMed2001

A study of the cortical processing of ano-rectal sensation using functional MRI.

Investigation of human ano-rectal physiology has concentrated largely on understanding the motor control of defecation and continence mechanisms. However, little is known of the physiology of ano-rectal sensation. There are important differences in the afferent innervation and sensory perception between the rectum and anal canal. This suggests that there could also be differences in the brain's processing of sensation from these two areas; however, this possibility remains unexplored. The aim of our study was to identify the cerebral areas processing anal (somatic) and rectal (visceral) sensation in healthy adults, using functional MRI. Eight male subjects with an age range of 21-39 years were studied on two separate occasions, one for rectal and the other for anal stimulation studies. Single shot gradient echo planar imaging was performed using a 1.5 tesla Phillips MRI scanner. For each subject, a series of 40 image sets containing 24 slices of the brain was obtained during periods of rapid phasic non-painful distension of the rectum or anal canal, alternating with rest periods, without stimulation. After motion correction, the images were analysed using cross correlation to identify the cerebral areas activated by the stimulus. Rectal stimulation resulted in bilateral activation of the inferior primary somatosensory, secondary somatosensory, sensory association, insular, peri-orbital, anterior cingulate and prefrontal cortices. Anal canal stimulation resulted in activation of areas similar to rectal stimulation, but the primary somatosensory cortex was activated at a more superior level, and there was no anterior cingulate activation. In conclusion, anal and rectal sensation resulted in a similar pattern of cortical activation, including areas involved with spatial discrimination, attention and affect. The differences in sensory perception from these two regions can be explained by their different representation in the primary somatosensory cortex. The anterior cingulate cortex was only activated by rectal stimulation, suggesting that the viscera have a greater representation on the limbic cortex than somatic structures, and this explains the greater autonomic responses evoked by visceral sensation in comparison with somatic sensation.

Adult↗
PubMed2001

Vagal afferent responses to fatty acids of different chain length in the rat.

The role of cholecystokinin (CCK) in the effect of dietary lipid on proximal gastrointestinal function and satiety is controversial. Recent work suggests that fatty acid chain length may be a determining factor. We investigated the mechanism by which long- and short-chain fatty acids activate jejunal afferent nerves in rats. Whole mesenteric afferent nerve discharge was recorded in anaesthetized male Wistar rats during luminal perfusion of saline, sodium oleate, and sodium butyrate (both 10 mM). Both fatty acids evoked characteristic afferent nerve responses, distinct from the mechanical response to saline, that were abolished in rats following chronic subdiaphragmatic vagotomy. The effect of oleate was abolished by the CCK-A receptor antagonist Devazepide (0.5 mg/kg), whereas the effect of butyrate persisted despite pretreatment with either Devazepide or a combination of the calcium channel inhibitors nifedipine (1 mg/kg) and the omega-conotoxins GVIA and SVIB (each 25 microg/kg). In summary, long- and short-chain fatty acids activate intestinal vagal afferents by different mechanisms; oleate acts via a CCK-mediated mechanism and butyrate appears to have a direct effect on afferent terminals.

Animals↗
PubMed2001

Central neural mechanisms mediating human visceral hypersensitivity.

Although visceral hypersensitivity is thought to be important in generating symptoms in functional gastrointestinal disorders, the neural mechanisms involved are poorly understood. We recently showed that central sensitization (hyperexcitability of spinal cord sensory neurones) may play an important role. In this study, we demonstrate that after a 30-min infusion of 0.15 M HCl acid into the healthy human distal esophagus, we see a reduction in the pain threshold to electrical stimulation of the non-acid-exposed proximal esophagus (9.6 +/- 2.4 mA) and a concurrent reduction in the latency of the N1 and P2 components of the esophageal evoked potentials (EEP) from this region (10.4 +/- 2.3 and 15.8 +/- 5.3 ms, respectively). This reduced EEP latency indicates a central increase in afferent pathway velocity and therefore suggests that hyperexcitability within the central visceral pain pathway contributes to the hypersensitivity within the proximal, non-acid-exposed esophagus (secondary hyperalgesia/allodynia). These findings provide the first electrophysiological evidence that central sensitization contributes to human visceral hypersensitivity.

Adult↗
PubMed2001

Physiology and pathophysiology of the swallowing area of human motor cortex.

Swallowing problems can affect as many as one in three patients in the period immediately after stroke. Despite this, in the majority of cases, recovery usually occurs to a safe level after a month or two. In this review, we show how the organization of the cortical projections to swallowing muscles can account for many of the clinical observations on swallowing after stroke and explain why recovery is common in the long term. In addition, we examine approaches that may be useful in speeding up recovery of swallowing. Swallowing may be a useful model in which to study central nervous reorganization after injury.

Deglutition↗
PubMed2000

Fatty acid-induced cholecystokinin secretion and changes in intracellular Ca2+ in two enteroendocrine cell lines, STC-1 and GLUTag.

1. Fatty acid-induced cholecystokinin (CCK) secretion in humans and from the enteroendocrine cell line STC-1 depends critically on acyl chain length. 2. Therefore we have characterized the relationship between acyl chain length and the potency of the fatty acid to induce CCK secretion and changes in intracellular Ca2+ concentration ([Ca2+]i) in two enteroendocrine cell lines (STC-1 and GLUTag). We found that the potency of the fatty acid was directly proportional to its chain length and therefore inversely proportional to its solubility. 3. In both cell types, the fatty acid-induced rise in [Ca2+]i in response to decanoic acid (C10), dodecanoic acid (C12) and tetradecanoic acid (C14) was significantly reduced in Ca2+-free medium and largely blocked by nicardipine. Intracellular stores also contributed to the overall shape of the [Ca2+]i peak. Thus all the fatty acids tested caused the release of Ca2+ from stores and influx of extracellular Ca2+, presumably through L-type calcium channels. 4. To probe the site of fatty acid action, we studied the distribution of 14C-labelled dodecanoic acid. This label was rapidly and irreversibly accumulated by both cell types, where it became concentrated about 20-fold. Confocal microscopy of a fluorescent analogue of dodecanoic acid clearly demonstrated that it entered the cytosol and was not merely partitioning in the cell membrane. These data indicate that an intracellular action for fatty acid-induced CCK secretion cannot be eliminated. 5. Dodecanoic acid itself, and not a metabolite, is the agent responsible for triggering Ca2+ entry since a non-metabolizable form of dodecanoic acid (2-bromododecanoic acid) was also capable of inducing a rise in [Ca2+]i in both cell types. 6. In conclusion, the rise in [Ca2+]i in STC-1 and GLUTag cells evoked by medium- to long-chain fatty acids results from the triggering of a specific signalling pathway. Whether triggering occurs through activation of a membrane-bound receptor or at an intracellular site remains to be clarified.

Calcium↗
PubMed2000

Contribution of central sensitisation to the development of non-cardiac chest pain.

BACKGROUND: Non-cardiac chest pain mimics angina pectoris but generally originates from the oesophagus. Visceral hypersensitivity may contribute, but its neurophysiological basis is unclear. We investigated whether central sensitisation, an activity-dependent amplification of sensory transfer in the central nervous system, underlies visceral pain hypersensitivity and non-cardiac chest pain. METHODS: We studied 19 healthy volunteers and seven patients with non-cardiac chest pain. Acid was infused into the lower oesophagus. Sensory responses to electrical stimulation were monitored within the acid-exposed lower oesophagus, the non-exposed upper oesophagus, and the cutaneous area of pain referral, before and after the infusion. FINDINGS: In healthy volunteers, acid infusion into the lower oesophagus lowered the pain threshold in the upper oesophagus (mean decrease 18.2% [95% CI 10.4 to 26.0]; p=0.01) and on the chest wall (24.5% [10.2 to 38.7]; p=0.01). Patients with non-cardiac chest pain had a lower resting oesophageal pain threshold than healthy controls (45 [30 to 58] vs 64 [49 to 81] mA; p=0.04). In response to acid infusion, their pain threshold in the upper oesophagus fell further and for longer (mean fall in area under threshold/time curve 26.7 [11.0 to 42.3] vs 5.8 [2.8 to 8.8] units; p=0.04). INTERPRETATION: The finding of secondary viscerovisceral and viscerosomatic pain hypersensitivity suggests that central sensitisation may contribute to visceral pain disorders. The prolonged visceral pain hypersensitivity in patients with non-cardiac chest pain suggests a central enhancement of sensory transfer. New therapeutic opportunities are therefore possible.

Adult↗
PubMed2000

Cortical processing of human somatic and visceral sensation.

Somatic sensation can be localized precisely, whereas localization of visceral sensation is vague, possibly reflecting differences in the pattern of somatic and visceral input to the cerebral cortex. We used functional magnetic resonance imaging to study the cortical processing of sensation arising from the proximal (somatic) and distal (visceral) esophagus in six healthy male subjects. Esophageal stimulation was performed by phasic distension of a 2 cm balloon at 0.5 Hz. For each esophageal region, five separate 30 sec periods of nonpainful distension were alternated with five periods of similar duration without distension. Gradient echoplanar images depicting bold contrast were acquired using a 1.5 T GE scanner. Distension of the proximal esophagus was localized precisely to the upper chest and was represented in the trunk region of the left primary somatosensory cortex. In contrast, distension of the distal esophagus was perceived diffusely over the lower chest and was represented bilaterally at the junction of the primary and secondary somatosensory cortices. Different activation patterns were also observed in the anterior cingulate gyrus with the proximal esophagus being represented in the right midanterior cingulate cortex (BA 24) and the distal esophagus in the perigenual area (BA32). Differences in the activation of the dorsolateral prefrontal cortex and cerebellum were also observed for the two esophageal regions. These findings suggest that cortical specialization in the sensory-discriminative, affective, and cognitive areas of the cortex accounts for the perceptual differences observed between the two sensory modalities.

Adult↗
PubMed2000

Identification of the optimal parameters for recording cortical potentials evoked by mechanical stimulation of the human oesophagus.

Cortical evoked potentials (CEP) have been recorded in response to both electrical stimulation (ES) and mechanical stimulation (MS) of the oesophagus. While the optimal parameters for recording reproducible oesophageal CEP to ES have recently been established, they have not yet been determined for MS, and reported CEP to MS show considerable variability. This study aimed to identify the optimal parameters required to record reproducible MS induced CEP. CEP were recorded from the vertex (Cz) in six subjects (one female; age range 23-47 years). MS was performed 5 cm above the lower oesophageal sphincter by rapidly inflating a 2-cm long silicone balloon at a frequency of 0.2 Hz. The rise time to maximum inflation was 165 ms. In order to determine the minimum number of stimuli required to produce optimal signal-to-noise quality, we acquired data in runs of 25, 50, 100 and 300 stimuli and to determine the stimulation intensity that produced the shortest latency and the largest amplitude CEP, we averaged four runs of 50 stimuli at five different intensities ranging from sensory threshold to pain. CEP reproducibility was then assessed in three subjects on three separate occasions using parameters determined from these measurements. We found that optimal signal-to-noise quality was achieved by averaging four runs of 50 stimuli; that P1 latency was shortest and P1-N1 amplitude largest at intensities of 75% and pain threshold and that highly reproducible CEP were obtained in all individuals. We conclude that it is possible to obtain highly reproducible oesophageal CEP to MS which can now be compared to those obtained by ES in order to identify which is most suitable for clinical studies.

Adult↗
PubMed2000

Comparison of cortical potentials evoked by mechanical and electrical stimulation of the rectum.

Patients with irritable bowel syndrome have heightened perception of gut sensation. The mechanisms responsible for this remain unknown, due to current poor knowledge of the central processing of gut sensation. Cortical evoked potentials (CEPs) have been recorded following both electrical rectal stimulation (ERS) and mechanical rectal stimulation (MRS). Because of the lack of a direct comparison of these two methods, their robustness for future clinical use remains unknown. The aim of our study was to compare the characteristics of CEPs following ERS and MRS. CEPs were recorded from the vertex in 14 healthy volunteers following ERS with bipolar ring electrodes, and MRS by repeated rectal distension. CEPs were recorded in all subjects following electrical stimulation, but only in 11 subjects following mechanical stimulation. In comparison with electrical stimulation, mechanical stimulation produced CEPs with a smaller amplitude and longer latency. However, the morphology of CEPs following electrical and mechanical rectal stimulation was similar, with no difference in the interpeak latencies. In conclusion, we have demonstrated that electrical rectal stimulation is a more reliable stimulus for recording CEPs. The similarity of the morphology and interpeak latencies of the CEPs suggests that both stimuli are activating a similar network of cortical neurones.

Adult↗
PubMed2000

A cortical evoked potential study of afferents mediating human esophageal sensation.

The aim of this study was to compare the characteristics of esophageal cortical evoked potentials (CEP) following electrical and mechanical stimulation in healthy subjects to evaluate the afferents involved in mediating esophageal sensation. Similarities in morphology and interpeak latencies of the CEP to electrical and mechanical stimulation suggest that they are mediated via similar pathways. Conduction velocity of CEP to either electrical or mechanical stimulation was 7.9-8.6 m/s, suggesting mediation via thinly myelinated Adelta-fibers. Amplitudes of CEP components to mechanical stimulation were significantly smaller than to electrical stimulation at the same levels of perception, implying that electrical stimulation activates a larger number of afferents. The latency delay of approximately 50 ms for each mechanical CEP component compared with the corresponding electrical CEP component is consistent with the time delay for the mechanical stimulus to distend the esophageal wall sufficiently to trigger the afferent volley. In conclusion, because the mechanical and electrical stimulation intensities needed to obtain esophageal CEP are similar and clearly perceived, it is likely that both spinal and vagal pathways mediate esophageal CEP. Esophageal CEP to both modalities of stimulation are mediated by myelinated Adelta-fibers and produce equally robust CEP responses. Both techniques may have important roles in the assessment of esophageal sensory processing in health and disease.

Adult↗
PubMed2000

Organization and reorganization of human swallowing motor cortex: implications for recovery after stroke.

Swallowing problems can affect as many as one in three patients in the period immediately after a stroke. In some cases this can lead to serious morbidity, in particular malnutrition and pulmonary aspiration. Despite this, swallowing usually recovers to a safe level in the majority of patients within weeks. This propensity for recovery is likely to relate to how the swallowing motor cortex is organized and then reorganized after cerebral injury. In this review, we examine present knowledge on the cortical control of swallowing in humans, and examine the aspects of its organization that are important for compensating for recovery after damage. In addition, we examine approaches which may be useful in speeding up the process of recovery. Swallowing may turn out to be a useful model for studying central nervous system plasticity.

Animals↗
PubMed1999

Fatty acid chain length determines cholecystokinin secretion and effect on human gastric motility.

BACKGROUND & AIMS: Fatty acids induce cholecystokinin (CCK) secretion and modify gastric motility, but the chain length requirements for these effects are not known. Nor is it clear whether the effects of fatty acids on gastric motility in humans are CCK mediated or directly exerted. The aim of this study was to determine the role of fatty acyl chain length in CCK secretion and in influencing gastric motility. METHODS: Fatty acids were infused into the upper gut in healthy volunteers; plasma CCK was determined by radioimmunoassay. Effects of fatty acids on antral contractility were determined by percutaneous ultrasonography; effects on proximal gastric tone were studied during fundal distention. RESULTS: Plasma CCK concentration was consistently and similarly elevated by fatty acids with a chain of 12 carbon atoms or longer, whereas those of 11 or fewer carbon atoms failed to increase plasma CCK. A 12-carbon but not a 10-carbon-long chain fatty acid reduced antral contractile amplitude, an effect that was abolished by loxiglumide (a specific CCK-A receptor antagonist). The 12-carbon fatty acid also reduced proximal gastric tone more than the 10-carbon fatty acid. CONCLUSIONS: A highly specific, chain length-sensitive fatty acid recognition system exists in the proximal gut mediating CCK secretion and gastric motility. An additional, probably CCK-independent, effect of fatty acid also regulates proximal gastric tone.

Adolescent↗
PubMed1999

Mutations of RegIalpha are associated with enterochromaffin-like cell tumor development in patients with hypergastrinemia.

BACKGROUND & AIMS: The RegIalpha gene (Reg) encodes a secretory protein proposed to regulate islet beta-cell and gastric mucous cell growth. Reg is expressed in rat gastric enterochromaffin-like (ECL) cells. The aim of this study was to examine Reg expression in human corpus and to determine the identity of Reg in ECL cell carcinoid tumors in hypergastrinemic patients. METHODS: Reg messenger RNA (mRNA) abundance was quantified by Northern blot in extracts of gastric corpus from patients with and without ECL cell tumors and in AR4-2J cells stimulated by gastrin; cellular origins were determined by immunocytochemistry. Mutations of Reg were determined by reverse-transcription polymerase chain reaction, cloning, and sequencing, and the mutated protein was expressed in HIT-T15 cells. RESULTS: Reg mRNA abundance was increased approximately threefold in the corpus of hypergastrinemic patients compared with controls, and was enriched in 3 of 7 ECL cell carcinoid tumors but not in non-endocrine cell gastric polyps. In AR4-2J cells, gastrin stimulated Reg mRNA abundance; this was eliminated by the gastrin/cholecystokinin B antagonist L-740,093 (10(-9) mol/L). Immunocytochemistry indicated that Reg was located in both chief cells and ECL cells in human corpus. Mutations of Reg were identified in 3 of 5 patients with ECL cell carcinoid tumors; in 2 cases, mutation of the initiator methionine residue led to exclusion of the protein from the secretory pathway. CONCLUSIONS: Gastrin regulates Reg mRNA abundance in human corpus. Mutations of Reg that prevent secretion are associated with ECL cell carcinoids, suggesting a function as an autocrine or paracrine tumor suppressor.

Adult↗
PubMed1999

The cortical topography of human anorectal musculature.

BACKGROUND & AIMS: The muscles of the anorectum are important in the volitional control of continence, yet virtually no information exists on their cortical representation in humans. METHODS: Topographic cortical mapping of both cerebral hemispheres was performed in 9 healthy subjects by applying suprathreshold transcranial magnetic stimulation to individual points on a scalp grid centered over the vertex and then recording the electromyographic responses from the external anal sphincter, rectum, and tibialis anterior muscles. RESULTS: Cortically evoked anal and rectal response latencies were similar (20.2 +/- 1.7 and 19.8 +/- 1.5 milliseconds, respectively) and were shorter than those from the anterior tibialis muscle (right, 29.7 +/- 2.3 milliseconds; left, 29.9 +/- 1.8 milliseconds; P < 0.0005). Cortical mapping showed that the anal responses were bilaterally represented on the superior motor cortex (Brodmann area 4) of both cerebral hemispheres; a similar topography was found for the rectal responses. By comparison, the tibialis responses showed predominantly contralateral medial motor cortex representation. Subtle but consistent differences in the degree of bilateral hemispheric representation were also apparent both between and within individuals for the anal responses and to a lesser extent for the rectal responses. CONCLUSIONS: The anorectal musculature has bilateral motor cortex representation with similar topography, but there is intersubject variation in the degree of symmetry.

Adult↗