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Biomedical subjects

D Grundy

Publications and source records attributed to D Grundy.

At least 73 records · Page 4Linked to original sources
PubMed1998

Mesenteric afferent sensitivity to cholecystokinin and 5-hydroxytryptamine.

The present electrophysiological investigation examines the effect of CCK and 5-hydroxytryptamine on gastrointestinal afferent fibre discharge. 5-HT markedly stimulated mesenteric afferents. The response was transient (< 10s) and mediated by 5-HT3 receptors as demonstrated by the action of 2-methyl-5-HT and antagonism by granisetron. CCK was also a potent stimulus to mesenteric afferents causing a long-lasting (> 30s) increase in excitability. The response to CCK was mediated via the CCKA receptor as shown by the antagonistic action of devazepide. At doses of granisetron and devazepide which completely block the response to exogenous 5-HT and CCK, the afferent fibres still responded to both mechanical and chemical stimulation of the mucosa. Thus products of enteroendocrine cells can have profound effects on mucosal afferent sensitivity but do not play an obligatory role in afferent signal transduction.

Animals↗
PubMed1997

Prolonged intestinal afferent nerve discharge in response to cholecystokinin-58 compared to cholecystokinin-8 in rats.

Intestinal afferents are sensitive to cholecystokinin (CCK) octapeptide. However, CCK-58 may be a more biologically relevant molecule. Therefore, recordings from jejunal mesenteric afferent bundles were secured for extracellular multi-unit recording and the responses to CCK-8 and CCK-58 compared. CCK-8 and CCK-58 (i.v.) evoked a dose-dependent, devazepide sensitive, increase in afferent nerve discharge. Peak discharge frequency was higher for CCK-8 at all doses (P < 0.05). However, response duration was more prolonged for CCK-58 (P < 0.05) at 200 pmol.kg(-1). This resulted in an overall increase in area under the curve of CCK-58 compared to CCK-8 (P < 0.05). CCK-58 stimulates afferent discharge in a different pattern than CCK-8 and, therefore, may have differential biological effects.

Afferent Pathways↗
PubMed1997

Effects of duodenal nutrients on sensory and motor responses of the human stomach to distension.

To study in healthy subjects the relationship between gastric sensations/perception and motility during gastric distension and the effects of duodenal nutrients, a flaccid gastric bag was distended in the proximal stomach with air at 100 ml/min while the duodenum was perfused (1 ml/min) with isotonic saline, hypertonic saline, glucose (1 kcal/ml), maltodextrin (2 kcal/ml), and 10% (1 kcal/ml) and 20% lipid (2 kcal/ml). Intragastric pressure was recorded continuously, and the subjects were asked to report gastric sensations. Compared with isotonic saline, all infusions significantly decreased gastric tonic and phasic pressure activity during gastric distensions and, with the exception of 20% lipid, caused fullness and discomfort during distensions to occur at larger volumes associated with lower intragastric pressures. Maltodextrin and 20% lipid changed fullness during distensions into a meal-like sensation. Only 20% lipid significantly increased the incidence of nausea. In conclusion, the sensory responses to gastric distension are modified by duodenal nutrients. Different nutrients result in different responses, but the responses obtained cannot be explained by changes in gastric pressure activity.

Adult↗
PubMed1996

Sensitivity of vagal mucosal afferents to cholecystokinin and its role in afferent signal transduction in the rat.

1. Extracellular recordings from rat mesenteric paravascular nerve bundles were made in order to characterize the responses of different populations of afferents supplying the small intestine to intravenous cholecystokinin (CCK; in the form of sulphated CCK8). 2. Approximately 70% of mesenteric nerve bundles contained CCK-sensitive afferent fibres. Responsive afferents had low spontaneous discharge (1.6 +/- 0.3 impulses s-1) and showed a 14-fold increase in firing at the peak of the response to 50 pmol CCK with the overall response lasting several minutes. The onset of the response occurred after a latency of (3.9 +/- 0.1 s) following i.v. administration of CCK, which corresponds largely to the circulation delay in these animals. The threshold dose of CCK was < 5 pmol. 3. The response to 100 pmol CCK was completely abolished by devazepide (0.5 mg kg-1) and by chronic subdiaphragmatic vagotomy performed 10-14 days prior to experimentation, indicating that CCK sensitivity was via CCKA receptors and exclusively mediated via vagal afferents rather than splanchnic or enteric afferents. 4. Evidence that CCK-sensitive afferents had mucosal receptive fields was indicated by the lack of any response to luminal distension and the sensitivity of the CCK response to luminal anaesthesia. Furthermore, CCK-sensitive afferents responded to luminal hydrochloric acid (50 mM) in a slowly adapting manner. The response to acid was significantly reduced (P < 0.005), but not abolished, by devazepide at a time when the response to exogenous CCK had been completely eliminated. 5. The exquisite sensitivity of some vagal mucosal afferents to CCK suggests that they may play a physiological role in the reflex and behavioural consequences of CCK release from the small intestine, possibly acting in a paracrine fashion. However, this sensitivity to CCK represents only one aspect of the broad chemosensitivity of these mucosal afferents and is not an obligatory component of the signal transduction pathway.

Afferent Pathways↗
PubMed1995

Fat increases vection-induced nausea independent of changes in gastric emptying.

Vection and fat delay gastric emptying and can induce nausea. Therefore, we studied the interaction between vection and fat on the production of nausea and the relationship between the severity of symptoms and changes in gastric emptying. Twelve healthy males consumed two liquid test meals, a zero-fat and a high-fat meal. Nausea was induced by seating the subjects inside a rotating vection drum. In protocol 1, drum rotation started immediately after ingestion of either meal; in protocol 2, when approximately 50% of each meal had emptied into the intestine. Gastric emptying was determined using gamma scintigraphy. Severity of symptoms was assessed throughout. Symptoms were similar for the high-fat and the zero-fat meal when vection was induced immediately after meal ingestion. Scores were only elevated by the high-fat meal when about half the meal had entered the intestine before vection was induced. No correlation was found between gastric emptying and the severity of symptoms. In conclusion, the interaction of vection and intraduodenal fat exacerbates nausea, but this effect is independent of a delay in gastric emptying.

Adult↗
PubMed1995

Inhibition of gastric mechanoreceptor discharge by cholecystokinin in the rat.

The aim of the present study was to investigate electrophysiologically the effect of systemic cholecystokinin (CCK) on the discharge of vagal gastric mechanoreceptors. Twenty-two single vagal afferent fibers were selected for the investigation of responses to intravenous CCK octapeptide (CCK-8) on the basis of a positive response to gastric distension. Resting discharge in these afferent fibers was 1.3 +/- 0.3 impulses.s-1 and increased to 9.2 +/- 0.9 impulses.s-1 during distension (P < 0.0001), CCK (20-100 pmol iv) caused a gastric relaxation of 2.1 +/- 0.2 cmH2O and inhibition of phasic motility. The discharge of 20/22 of vagal tension receptors closely followed the magnitude and time course of the fall in pressure. Mean discharge before and after CCK (50 pmol) was 7 +/- 0.9 and 3.9 +/- 0.8 impulses.s-1, respectively (P < 0.001, n = 22). Both the pressure response and the concomitant changes in afferent discharge were abolished by L-364,718 (1.2 mg/kg iv). Only two afferent units failed to show a decrease in firing following CCK (50 pmol), and at 500 pmol the discharge of these units was augmented. In conclusion, CCK (50 pmol) has predominantly indirect effects on gastric mechanoreceptors, which decrease their firing in association with gastric relaxation.

Animals↗
PubMed1995

Gastric emptying and the symptoms of vection-induced nausea.

OBJECTIVES: To examine the hypothesis that nausea during vection arises directly from an underlying alteration in gastric motility. DESIGN: The simultaneous application of vection and assessment of gastric emptying of a liquid, non-nutrient test meal allowed the examination of the interaction between changes in gastric motility and symptoms. METHODS: Studies were conducted in 14 volunteers. Vection was induced by seating the subject inside a rotating circular drum, which was painted with vertical black and white stripes. In the control study (n = 8) the drum was not rotated. Gastric emptying was measured by gamma scintigraphy of a radiolabelled isosmotic saline test meal. RESULTS: Vection induced upper abdominal sensations (epigastric awareness) in 10 subjects, eight of whom subsequently reported nausea; autonomic symptoms of sweating and pallor were experienced by 12 subjects. Two subjects remained completely asymptomatic during vection. None of the subjects experienced any sensations during the control study. Gastric emptying was significantly delayed during vection (P < 0.01). There was a highly significant correlation between gastric emptying and the intensity of nausea. However, examination of the gastric emptying profiles did not support any direct association between altered gastrointestinal motor activity and symptoms. Two subjects with slowing of gastric emptying exhibited no nausea or upper abdominal symptoms, while another two experienced nausea when the underlying rate of gastric emptying was similar to that of the control period. CONCLUSIONS: The delay in gastric emptying of a liquid test meal induced by vection appears to be a variable epiphenomenon of nausea. A cause and effect relationship between gastric emptying and nausea therefore appears unlikely.

Adult↗
PubMed1994

Role of 5-hydroxytryptamine in gastrointestinal chemosensitivity.

The present electrophysiological investigation examines the effect of 5-hydroxytryptamine (5-HT) on gastrointestinal afferent fiber discharge. 5-HT markedly and specifically stimulated vagal mucosal chemosensitive afferents. The response was mediated by 5-HT3 receptors as demonstrated by the action of 2-methyl-5-HT and antagonism by granisetron. At doses of granisetron that completely block the response to 5-HT, the afferent fibers still responded to both mechanical and chemical stimulation of the mucosa. This sensitivity of extrinsic afferents is in marked contrast to that reported for intrinsic afferents, suggesting fundamental differences in the organization of enteric and vagal reflexes.

Animals↗
PubMed1993

Role of nitric oxide and vasoactive intestinal polypeptide in vagally mediated relaxation of the gastric corpus in the anaesthetized ferret.

The roles of VIP and NO in vagally mediated relaxations of the gastric corpus were investigated in the anaesthetized ferret. Intracorpus pressure was recorded manometrically during electrical stimulation of the cervical vagus nerve in three groups of animals: one control group (n = 6), one group treated with an inhibitor of NO synthesis (NG-nitro-L-arginine methyl ester (L-NAME), 1.6 mg/kg); and a third group which had been immunized, prior to the experiment, with a VIP-thyroglobulin conjugate (25 nmol equivalent) in Freund's complete adjuvant. In control animals, following treatment with atropine (100 micrograms/kg), vagal stimulation resulted in a frequency dependent fall in intracorpus pressure with the maximum response at 5 Hz of 2.2 +/- 0.3 cm H2O. Two components of the response could be observed: an initial rapid fall over the first 10 s of stimulation followed by a slower decline over the remainder of the stimulation period. In animals treated with L-NAME (n = 6) the initial rapid response was significantly reduced at all frequencies of stimulation (P < 0.05 - P < 0.005, Mann-Whitney U-test) leaving only the slower second component. In immunized animals (n = 6) the initial rapid response to vagal stimulation was not different from control but the slower second component was significantly reduced at 1 Hz (P < 0.005). We conclude that the response to vagal stimulation appears to consist of two components which can be differentiated using L-NAME and autoimmunization to VIP.

Anesthesia↗
PubMed1993

Effects of 5-hydroxytryptamine on discharge of vagal mucosal afferent fibres from the upper gastrointestinal tract of the ferret.

This study was undertaken to determine the effects of 5-hydroxytryptamine (5-HT) on vagal mucosal afferent endings and how this may relate to their sensitivity to other stimuli. Single afferent fibres with receptive fields in the mucosa of the upper gastrointestinal tract were recorded from the cervical vagus of Urethane anaesthetized ferrets. The selection criteria included failure to respond to luminal distension (i.e., vagal tension receptors were excluded). All fibres tested responded to mucosal stroking. The majority of these (28/32) also responded to close-intrarterially applied 5-HT (10 micrograms) with a brief burst (usually < 15 s) of action potentials, which in 6/6 cases was reduced or abolished by the 5-HT3 receptor antagonist granisetron (0.1-0.5 mg/kg i.v.), as were four responses to cholecystokinin-octapeptide (100-400 pmol close I.A.). The response to 5-HT was shown to be dose-dependent over the dose range 2-75 micrograms on six occasions. Responses to luminal stimuli, which included 150 mM HCl, 1 M NaCl, and mucosal stroking, were not blocked by granisetron although in three fibres, the resting discharge was reduced by the antagonist, suggesting that resting discharge in vagal mucosal afferents may be influenced by endogenously released 5-HT.

Action Potentials↗
PubMed1993

Effects of 5-hydroxytryptamine (5-HT) on the discharge of vagal mechanoreceptors and motility in the upper gastrointestinal tract of the ferret.

This study was undertaken to investigate the sensitivity of vagal mechanoreceptor afferent fibres from the stomach and small intestine to 5-hydroxytryptamine (5-HT, 10 and 50 micrograms), and to relate this to motor activity. The discharge of single afferent fibres was recorded from the cervical vagus of Urethane anaesthetized ferrets. These had receptive fields in the corpus (15 fibres), antrum (11 fibres), duodenum (3 fibres) or jejunum (1 fibre), and their discharge was excited by distension of the segment containing the receptive field, or by mechanical probing. Conduction velocity was calculated in 7 fibres, and always fell in the C-fibre range (0.84 +/- 0.07 m/s). Injection of 5-HT intra-arterially via the coeliac axis evoked both contraction and relaxation with the dominant effect dependent on region and dose of 5-HT. However, irrespective of the motor response, the mechanoreceptor discharge closely mirrored both the magnitude and the time-course of the motor response. The relationship between the changes in discharge of individual mechanoreceptors and change in intraluminal pressure in all regions in response to both doses of 5-HT fitted a linear regression y = 17.1 +/- 1.2x and was highly significant (P < 0.0001), indicating that 5-HT has no modulatory effect on the sensitivity of mechanoreceptors to changes in intraluminal pressure. This study suggests that vagal mechanoreceptors supplying the gastrointestinal tract respond to changes in motor activity evoked by 5-HT, rather than to 5-HT directly.

Animals↗
PubMed1993

Limb blood flow, cardiac output and quadriceps muscle bulk following spinal cord injury and the effect of training for the Odstock functional electrical stimulation standing system.

As part of the assessment of the Odstock functional electrical stimulation (FES) standing system for mid to low thoracic lesion spinal cord injured (SCI) subjects, cardiac output, high blood flow and quadriceps muscle thickness were measured before and following an electrical stimulation muscle retraining programme. The same parameters were also measured in a group of uninjured subjects and in SCI subjects. It was found that there was no difference in cardiac output between the groups. However thigh blood flow was found to be around 65% of normal values in the spinally injured group. This returned to normal values following the retraining programme. The quadriceps muscle wasted to approximately 50% of its original thickness in the first 3 weeks following spinal cord injury. The retraining programme increased the muscle thickness to near normal values.

Adult↗
PubMed1993

Carcinoma of the scrotum associated with rubber urinals. Case report.

A paraplegic patient, who had worn a rubber urinal in close contact with the scrotum for over 40 years, developed carcinoma of the scrotum. It is likely that this is a previously unsuspected example of chemical carcinogenesis, and in view of this, we believe that the use of rubber urinals should be discontinued.

Carcinoma, Squamous Cell↗
PubMed1993

Effect of varying the rate and pattern of gastric distension on its sensory perception and motor activity.

The aim of the present study was to see if varying the rate and pattern of gastric distension affected its motor and sensory responses to distension. A balloon was used to carry out distensions in male volunteers at constant rates of 20, 50, 100, and 200 ml/min. In addition rapid (75 ml/s) intermittent distensions (RID) were carried out with the use of a large hand-held syringe. Subjects were asked to indicate the first perception of the balloon, fullness, and discomfort. Increasing the rate of ramp distension caused all sensations to occur at higher volumes and higher pressures and reduced the frequency and amplitude of phasic oscillations in gastric pressure. During RID, the same sensations were experienced at much reduced volumes but were poorly sustained. These data suggest that ramp and RID are likely to induce gastric sensations by activating different populations of receptors. The responses to ramp distension are compatible with the activation of stretch receptors situated in parallel with the muscle elements, whereas RID appear to be activating a different population of rapidly adapting mechanoreceptors possibly situated in the mucosa.

Adult↗
PubMed1993

Plasticity in the gastric inhibitory innervation after immunization against VIP and vagotomy in the ferret.

Changes in gastric corpus tone have been characterized during two procedures that compromise the major inhibitory innervation of the stomach: immunoneutralization of endogenous vasoactive intestinal polypeptide (VIP) and chronic vagotomy. After both procedures, there was a small but significant increase in intracorpus pressure generated during ramp increases in volume compared with sham immunized controls but not when the procedures were combined in vagotomized immunized animals. Adaptation in the mechanisms controlling corpus tone was most apparent after atropine (100 micrograms/kg) and acute vagal section when tone was low in sham immunized vagotomized and vagotomized immunized animals (4.4 +/- 0.3 and 3.7 +/- 0.8 cmH2O, respectively) and high in immunized and sham immunized animals (6.5 +/- 0.4 and 6.2 +/- 0.5 cmH2O) despite a similar sensitivity to atropine. Corpus responses to low-frequency vagal stimulation were maintained in immunized animals despite the absence of a response to exogenous VIP. We conclude that gastric reservoir function adapts to the loss of the vagal inhibitory innervation by an upregulation of intrinsic reflex pathways controlling myenteric inhibitory neurons, which are non-VIPergic.

Animals↗