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D G Thompson

Publications and source records attributed to D G Thompson.

At least 73 records · Page 4Linked to original sources

Characterization of cholecystokininA and cholecystokininB receptors expressed by vagal afferent neurons.

The cholecystokinin receptors expressed by vagal afferent neurons mediate the effect of cholecystokinin in inhibiting food intake and gastric emptying. We have determined the relative abundance of cholecystokininA, gastrin-cholecystokininB and gastrin-cholecystokininC receptor populations in the rat vagus by autoradiography using [125I]Bolton Hunter-cholecystokinin-8, [125I]Bolton Hunter-heptadecapeptide gastrin and [125I]Leu(15)2-17Glycine-extended heptadecapeptide gastrin, together with the selective antagonists devazepide and L-740093. The results indicate approximately three-fold higher abundance of cholecystokininA compared with gastrin-cholecystokininB receptors, and no significant representation of gastrin-cholecystokininC receptors. Topical capsaicin applied to the vagal nerve trunk abolished the accumulation of sites binding both [125I]Bolton Hunter-labelled cholecystokinin-8 and heptadecapeptide gastrin indicating that both cholecystokininA and gastrin-cholecystokininB receptor populations were present on afferent fibres. The molecular identity of the receptors expressed by rat and human nodose ganglia was examined using the reverse transcription polymerase chain reaction. Products of the predicted size for the cholecystokininA and gastrin-cholecystokininB receptors were identified. The human and rat cholecystokininA receptor products were cloned and the sequences were found to be 99% homologous to those published for receptors expressed by rat pancreas and human gall bladder. We conclude that cholecystokininA and gastrin-colecystokininB receptors are synthesized by nodose ganglion cells, and that the receptor proteins are transported to the periphery along afferent fibres. While there is a clear role for vagal cholecystokininA receptors, the function of vagal afferent gastrin-cholecystokininB receptors remains to be determined.

Afferent Pathways↗

Topographic mapping of trans-cranial magnetic stimulation data on surface rendered MR images of the brain.

We present a method for the coregistration and topographic mapping of trans-cranial magnetic stimulation (TCMS) data on surface rendered images of the cortex, derived from Magnetic Resonance Images (MRI). We describe the TCMS procedure and the methods used to locate the TCM stimulation sites in the MRI coordinate system, and the algorithms needed to depict the TCMS distribution as a pseudocolour contour map on the cortical surface. The methods are validated using TCMS data from the hand (thenar) and leg (tibialis muscle). The methods used correctly depict the expected motor representations of each of these areas and we therefore propose that this technique may be used as a functional imaging tool in the investigation of cortical function in both normals and patients.

Brain Mapping↗

Gastrin biosynthesis in the antrum of patients with pernicious anemia.

BACKGROUND & AIMS: The gastrin precursor progastrin produces multiple alternative active products, but the pathways of posttranslational processing in human antral mucosa have not yet been studied directly. The aim of this study was to investigate the biosynthetic relationships and release kinetics of newly synthesized progastrin-derived peptides in the antrum of patients with pernicious anemia. METHODS: Antral mucosal explants were incubated with [35S]sulfate and [3H]tyrosine to label progastrin and its derivatives, which were detected by online scintillation counting after immunoprecipitation and high-performance liquid chromatography. RESULTS: [35S]- and [3H]progastrin were detected within 2.5 hours, and labeled G34Gly and G34 were readily detected after 5-hour incubation. Pulse-chase studies indicated conversion of progastrin to G17 via G34Gly and G34. Secretion of newly synthesized G34, but not G34Gly, was routinely detected; G17Gly was present only in trace quantities in cell extracts and media. In control samples, progastrin synthesis was about 10 times lower than in pernicious anemia samples, although the proportions of different labeled amidated gastrins after 5-hour incubation were similar. CONCLUSIONS: In the antrum of patients with pernicious anemia, Gly-gastrins, particularly G34Gly, are biosynthetic intermediates and not major secretory products. Some G34 is secreted preferentially under basal conditions.

Aged↗

Relation between cholecystokinin and antral innervation in the control of gastric emptying in the rat.

BACKGROUND: Antral motility and the hormone cholecystokinin (CCK) are major determinants of the rate of gastric emptying. The relation between CCK and antral neurons in regulating gastric emptying is uncertain. Benzalkonium chloride (BAC) causes selective lesions in gut myenteric neurons after serosal application. AIM: To develop a model of antral denervation using BAC to enable the study of the relation between CCK and antral neurons in regulating gastric emptying. METHODS: BAC, vehicle or the afferent neurotoxin capsaicin were applied to the serosal surface of the rat antrum or corpus; neurochemical markers of intrinsic and afferent neurons were detected by using immunohistochemistry and radioimmunoassay. Gastric retention of solids was determined after fasting, and emptying of liquids was measured in rats with gastric fistulae. RESULTS: In BAC treated rats radioimmunoassay of tissue extracts revealed a dose related specific loss of gastrin releasing peptide, substance P, and vasoactive intestinal polypeptide immunoreactivities from the treated region, and immunohistochemistry revealed loss of the neuronal marker PGP 9.5 and the afferent neuropeptide calcitonin gene related peptide (CGRP). Adjacent untreated regions were unaffected by BAC, with the exception that CGRP was depleted in both corpus and antrum after antral treatment. After antral BAC treatment fasted rats retained solids for over 48 hours. Moreover, in antrally denervated rats with gastric fistulae, the emptying of saline, acid and peptone was delayed substantially. The CCK dependent inhibition of gastric emptying of peptone was preserved after antral treatment with BAC. CONCLUSIONS: Serosal BAC causes lesions in the innervation of the treated region of the stomach. The innervation of the antrum is essential for normal emptying of both liquids and solids, but the inhibition of gastric emptying produced by CCK is not dependent on antral neurons.

Animals↗

Cranial nerve modulation of human cortical swallowing motor pathways.

Animal data indicate that cortical swallowing pathways can be modulated by cranial nerve afferent stimulation. We therefore studied the effects of human trigeminal and vagal nerve excitation on the corticofugal pathways to the oropharynx and esophagus, using electromagnetic stimulation. Unilateral stimulation of either the trigeminal or vagus nerve evoked two distinct reflex electromyographic responses in the pharynx and esophagus, an early response (latency range 19-30 ms) and a late response (latency range 42-72 ms). In the mylohyoid muscles, however, only a single response was seen (latency range 36-64 ms). Cortical stimulation also evoked electromyographic responses in the mylohyoid muscles, pharynx, and esophagus, with latencies of 8.5 +/- 0.3, 9.3 +/- 0.3, and 10.1 +/- 0.4 ms, respectively. When either trigeminal or vagus nerve stimulation preceded cortical stimulation, the cortically evoked responses were facilitated, with maximal effects at interstimulation intervals of 30-200 ms for pharynx and esophagus (P < 0.02) and at interstimulation intervals of 50-100 ms for mylohyoid muscles (P < 0.05). Our results demonstrate that stimulation of human cranial nerve afferent fibers facilitates cortical swallowing motor pathways.

Adult↗

Effect of cholecystokinin-A receptor blockade on lipid-induced gastric relaxation in humans.

The purpose of this study was to assess the role of endogenous cholecystokinin (CCK) in regulating fat-induced changes in human gastric relaxation. Proximal gastric pressure-volume relationships were determined in 12 healthy volunteers during a series of gastric distensions, both fasting and after intragastric instillation of 250 ml of 10% Intralipid. All subjects were studied twice, in a randomized, double-blind study, during intravenous infusion of either loxiglumide (CCK-A antagonist) or saline. For each distension, intragastric pressure and compliance were determined together with perception intensity. During saline infusion, Intralipid reduced intragastric pressure (prelipid, 11.7 +/- 0.8; postlipid, 9.7 +/- 0.6 mmHg; P = 0.002) and increased compliance (pressure-volume slope values: prelipid, 87.6 +/- 9.7; postlipid, 47.2 +/- 7; P < 0.01). Loxiglumide infusion during fasting exerted no effect on either intragastric pressure or compliance. After lipid, however, loxiglumide abolished the expected postlipid reduction in intragastric pressure (prelipid, 12.1 +/- 0.7; postlipid, 11.5 +/- 0.8 mmHg; P = 0.4) but did not consistently abolish the postlipid increase in compliance. Loxiglumide exerted no effect on the cumulative perception score or on the volume at perception threshold, although it prevented the fat-induced reduction in pressure at perception threshold [control: prelipid, 15.4 +/- 1.1; postlipid, 10.7 +/- 0.5 (P < 0.05); loxiglumide: prelipid, 13.8 +/- 1.5; postlipid, 12.2 +/- 0.9 (P > 0.05)]. Endogenous CCK or CCK-A receptors therefore play a role in the fat-induced reduction of intragastric pressure and might also modulate gastric perception after lipid.

Adult↗

The topographic representation of esophageal motor function on the human cerebral cortex.

BACKGROUND & AIMS: Corticofugal pathways to the human esophagus have been recently identified in humans using transcranial magnetic stimulation. The aim of this study was to determine the topographic representation of the esophagus on the cerebral cortex. METHODS: Focal magnetic stimulation of 1-cm areas was performed over both hemispheres in 10 healthy subjects. Esophageal electromyographic responses were recorded 2 cm below the upper esophageal sphincter. The studies were repeated to determine reproducibility in 3 subjects; in 2 subjects, esophageal topography was compared with thenar muscle topography. RESULTS: In all subjects, esophageal electromyographic responses were evoked by stimulation of either the right or left hemisphere. Largest amplitude responses were obtained anterior to those of the thenar muscles, indicating that the esophagus may be represented on either the anterior aspect of the motor cortex or on the premotor cortex. In all subjects, the area of response was asymmetric, being more extensive on the right hemisphere than on the left hemisphere in 8 subjects. In 2 subjects, the area of response on the left hemisphere was more extensive than on the right. Repeat studies showed that this asymmetry was consistent. CONCLUSIONS: Esophageal motor function shows bilateral cortical representation with consistent interhemispheric asymmetry.

Adult↗

The cortical topography of human swallowing musculature in health and disease.

Because no detailed information exists regarding the topographic representation of swallowing musculature on the human cerebral cortex in health or disease, we used transcranial magnetic stimulation to study the cortical topography of human oral, pharyngeal and esophageal musculature in 20 healthy individuals and the topography of pharyngeal musculature in two stroke patients, one with and one without dysphagia. Our results demonstrate that swallowing musculature is discretely and somatotopically represented on the motor and premotor cortex of both hemispheres but displays interhemispheric asymmetry, independent of handedness. Following stroke, dysphagia appeared to be associated with smaller pharyngeal representation on the intact hemisphere, which increases in size with recovery of swallowing.

Adolescent↗

Evaluation of gastric antral motor performance in patients with dysmotility-like dyspepsia using real-time high-resolution ultrasound.

Although manometric antral hypomotility and delayed gastric emptying have been reported separately in patients with dyspepsia, relationships between symptoms, antral contractility and emptying rate have not been sought. The present study therefore aimed to evaluate, simultaneously, gastric antral excursion characteristics and emptying in a sub-group of patients with severe functional dyspepsia using high-resolution real-time ultrasound. The circumference of the relaxed and contracted antrum was measured at 15-min intervals after ingestion of a 360 mL mixed nutrient meal in 36 chronic dyspepsia patients with symptoms of post-prandial bloating and epigastric distension, and in 25 healthy volunteers. Antral emptying (measured as the rate of decrease in circumference of the relaxed antrum) was slower in patients than normals (P = 0.02). In both groups, the average values for antral excursion were similar but the range of excursion in patients was significantly wider than in controls (F < 0.001), with 11 patients showing values above, and 8 showing values below the normal range. There was no relationship between antral emptying and antral excursion in either patients or volunteers. In conclusion, patients with severe functional dyspepsia show a wide range of antral performance characteristics, suggesting not only that the mechanisms responsible for the control of antral motor function are disturbed but also that the cause of the symptoms and the disturbed antral motor function are probably not directly related.

Adult↗

Nursing management of the infant with a congenital malignancy.

Care of the newborn diagnosed with a congenital malignancy is a challenge for the neonatal intensive-care unit nurse. Malignancies found in infants differ from those found in older children. Nursing care of the neonate suspected or diagnosed with congenital malignancy includes standard practices and problem identification as well as interventions unique to the patient with cancer. This article reviews the incidence, diagnosis, treatment, and nursing management of neoplasms diagnosed in neonates.

Antineoplastic Agents↗

Effect of distension and feeding on phasic changes in human proximal gastric tone.

BACKGROUND: Proximal stomach by virtue of its property of accommodation acts as a reservoir for the ingested food, but its role in emptying and the factors modulating it remain unexplored. AIM: To assess the effects of distension and of feeding on proximal gastric tone. SUBJECTS: 14 healthy volunteers with no current or past history of any gastro-intestinal symptoms. METHODS: Isobaric changes in volume of the proximal stomach were recorded both during fasting and for the first 30 minutes after a meal. RESULTS: For a given degree of distension, the mean (SEM) intragastric pressure was consistently lower, immediately after meal ingestion (9.8 (1.1), mm Hg) than during fasting (12.9 (0.6) mm Hg; p < 0.01). Proximal gastric tone was continuously variable with a frequency of fluctuation of 0.9-1.3/minute and an amplitude of 16.8 (2.2) ml, superimposed upon slower higher amplitude fluctuations in baseline tone. These variations in tone were unaffected by the degree of gastric distension or by food. CONCLUSIONS: While proximal gastric tone decreases after meal ingestions consistent with accommodation, the fluctuations in tone are not an importance factor in the modulation of nutrient emptying from the proximal stomach in the immediate postprandial period.

Adult↗

Modulation of esophageal responses to magnetic stimulation of the human brain by swallowing and by vagal stimulation.

BACKGROUND & AIMS: Although magnetic stimulation of the human cerebral cortex activates corticoesophageal pathways, it is not known whether these pathways are mediated via brain stem neurons activated during swallowing and by vagal afferents. The aim of this study was to determine the effect of swallowing and vagal stimulation on esophageal electromyographic responses evoked by magnetic stimulation of the human cortex. METHODS: Magnetic stimulation of the cortex was performed in 7 subjects at variable intervals after swallows and at intervals ranging from 10 to 200 milliseconds after vagal stimulation in 5 subjects. RESULTS: Between swallows, cortical stimulation induced both early (10.1 +/- 0.5 milliseconds) and late (52.3 +/- 2.3 milliseconds) esophageal electromyographic responses with amplitudes of 66.9 +/- 23.4 microV and 32.9 +/- 7.4 microV, respectively. During swallowing, both responses were facilitated because their latencies decreased (8.9 +/- 0.5 milliseconds and 47.3 +/- 4.8 milliseconds, respectively), whereas their amplitudes increased (203.1 +/- 54 microV and 79.8 +/- 22.5 microV, respectively). Vagal stimulation facilitated the early cortically evoked response. Its latency decreased from 10.2 +/- 0.2 milliseconds to 8 +/- 0.2 milliseconds, whereas its amplitude increased from 145.1 +/- 44 microV to 230.5 +/- 41.6 microV. CONCLUSIONS: Corticoesophageal pathways activated by magnetic stimulation of the human cortex share the same population of brain stem motor neurons to the upper esophagus that are activated during swallowing and vagal stimulation.

Adult↗

Topographic mapping of cortical potentials evoked by distension of the human proximal and distal oesophagus.

We describe cortical potentials evoked by balloon distension of the proximal and distal oesophagus in 8 healthy right handed volunteers. Oesophageal stimulation was performed using a pump which rapidly inflated a 2 cm silicone balloon positioned either 3 cm distal to the upper oesophageal sphincter or 5 cm proximal to the lower oesophageal sphincter, at a frequency of 0.2 Hz, using inflation volumes which produced a definite but not painful sensation. Oesophageal evoked cortical potentials were recorded in all subjects with an initial negative and positive component (N1 and P1), followed by a second negative and positive component (N2 and P2) in 6 subjects. The morphology and the scalp topography of the N1 component elicited by proximal and distal oesophageal stimulation suggests activation of the primary somatosensory cortex and/or the insular. There was also evidence for hemispheric dominance for the N1 potential which was independent of handedness. The frontal emphasis of the proximal oesophageal N1 component, in contrast to the central emphasis of the distal oesophageal N1 component, suggests that different neuronal populations were activated by stimulation of the two sites. The frontal emphasis of the ensuing P1 component from both oesophageal sites suggests that it originates in a separate precentral source. The topography of the N2 components obtained by stimulation of either oesophageal site was similar to that of the N1 component, suggesting that they originate in similar areas of the cortex. The P2 component evoked by stimulation of both oesophageal sites was localised at the vertex. The inter- and intra-subject variation in the morphology of the N2 and P2 components suggests that secondary cortical processes related to cognition may be involved in their generation.

Adult↗

Relations between upper abdominal symptoms and gastric distension abnormalities in dysmotility like functional dyspepsia and after vagotomy.

Postprandial bloating and fullness are commonly found both in dysmotility like functional dyspepsia, and after vagotomy but the relation between gastric accommodation and symptom production has not been investigated. Intragastric pressure levels and symptoms developed during controlled distension of the gastric fundus were recorded in nine patients with functional dyspepsia, in seven patients after truncal vagotomy, and in 11 healthy volunteers. The procedure was repeated after ingestion of a liquid nutrient meal (250 ml; 250 kcal). Gastric tone, expressed as the average value of pressure over the distension period was lower in controls (median: 11.3 mm Hg) than in either the dyspeptic patients (median: 16.48 mm Hg) or postvagotomy patients (median: 19.12 mm Hg) (p < 0.05). Meal ingestion reduced gastric tone in controls, but no significant change occurred in either the dyspepsia or the postvagotomy patients. Volumes at which discomfort was elicited by distension during fasting were lower both in dyspeptic patients (median: 210 ml) and in postvagotomy patients (median: 180 ml) than in healthy volunteers (median: 660 ml) (p < 0.05). Discomfort thresholds were unaffected by meal ingestion. These results suggest that a disturbance of gastric relaxation may be related to symptom development in dysmotility like functional dyspepsia, while similarities between dyspeptic patients and postvagotomy patients suggest that the impaired gastric accommodation in functional dyspepsia may be due to an underlying vagal defect.

Adult↗