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Biomedical subjects

D G Thompson

Publications and source records attributed to D G Thompson.

At least 109 records · Page 6Linked to original sources
PubMed1992

Modulation of human upper intestinal nutrient transit by a beta adrenoreceptor mediated pathway.

To explore the role played by beta adrenoreceptor mediated pathways on human upper gut function a series of studies were conducted into the effects of beta adrenoreceptor agonists and antagonists on orocaecal and duodenocaecal transit and on antral and duodenal motor activity. Under control conditions orocaecal transit was consistent within individuals (mean coefficient of variation (18.0%) but varied widely between individuals (median transit 63 minutes, range 33-164). Prior administration of the non-selective beta adrenergic antagonist propranolol consistently hastened orocaecal transit (median transit 51:25-93, v control p < 0.005). The selective beta-1 antagonist, atenolol, also hastened transit (median transit 50:35-93 minutes, v control p < 0.01). The magnitude of an individual's response to beta blockade correlated closely with the orocaecal transit (Tau = 0.54, p < 0.01). Duodenocaecal transit was also hastened by propranolol from control values of 66:45-107 minutes to 50:16-62 minutes, p < 0.025). In contrast neither duodenal nor antral motility were consistently altered by beta blockade. The beta adrenoreceptor agonist, isoprenaline, delayed both orocaecal transient (97:55-178 minutes, v control p < 0.005) and also duodenocaecal transit (160:45-215 minutes, v 73:40-133) (p < 0.025). Isoprenaline also reduced antral motility by an effect which appeared to occur predominantly through a reduction in contraction amplitude (from a median amplitude of 27:5.39 mm Hg to 14:3-24 mm Hg, p < 0.03) rather than an effect on the interval between contractions. No effect on either amplitude or frequency of duodenal motor activity was observed. A beta adrenoreceptor mediated pathway thus appears to exert a biologically relevant effect on gut function not only under conditions of sympathetic stimulation, but also at rest when a basal beta adrenergic tone appears to influence the speed of nutrient transit through the human upper gut.

Adult↗
PubMed1992

Effect of glyceryl trinitrate on proximal stomach musculature in normal volunteers.

UNLABELLED: The effect of GTN on stomach is unknown although there is evidence that nitric oxide, the active component of GTN have a mediator role in the upper gastrointestinal tract. By the use of a newly developed barostat technique it was investigated the effect of GTN on gastric fundal tone and contractions. METHOD: measurements were done 1 hour before an 1 hour after the administration of either 500 micrograms sublingual GTN and 5 mg buccal GTN or a placebo in 7 healthy individuals (14 experiments) by recording variations in the volume of air within an intragastric bag that was maintained at a constant pressure of 12 mmHg by the barostat. RESULTS: a significant increase in intrabag volume of 99.74 +/- 28.34 ml (mean +/- SEM) (p < 0.01) was recorded after GTN administration; a not significant (p > 0.01) increase in volume of 24.34 +/- 16.23 ml was after placebo. There was no significant difference between the frequency of contractions before and after drug or placebo administration. CONCLUSION: after systemic and constant administration of GTN a constant reduction in gastric fundal tone is produced with no change of fundal contractions.

Adult↗
PubMed1990

Inter- and intraindividual variation in pressure-volume relations of the rectum in normal subjects and patients with the irritable bowel syndrome.

The relation between intrarectal volume and pressure during increasing rectal distension by a latex balloon were studied on repeated occasions in 10 healthy adult volunteers to define variations within and between individuals. A wide intersubject variation in the maximum tolerable volume (58-908 ml) and pressure (12.2-108.8 cm H2O) at this end point was seen, and these two values were correlated (r = 0.78). Intrasubject variation in maximum tolerable volume also occurred which was related to study order and progressively reduced with repeated study. In 26 unselected patients with pain predominant irritable bowel syndrome similar intersubject variation was noted and virtually all patients data fell within the calculated 95% confidence limits of the normal individuals. Differentiation between patients and normal subjects was not possible from knowledge of rectal responses. These noticeable inter- and intrasubject variations in rectal responses to distension need to be considered whenever similar techniques are proposed for use in the study of rectal disease or of rectal response to treatment.

Adolescent↗
PubMed1990

Comparison of omeprazole and cimetidine in reflux oesophagitis: symptomatic, endoscopic, and histological evaluations.

Symptomatic patients with endoscopically verified reflux oesophagitis were randomised to a double blind trial in which they received either omeprazole (20 mg once daily) or cimetidine (400 mg four times daily) for four, and if necessary, eight weeks. In an 'intention to treat' analysis, oesophagitis was found to have healed after four weeks in 77 of 137 (56%) in the omeprazole group and in 34 of 133 (26%) in the cimetidine group (p less than 0.001). By eight weeks these values were 71% and 35% respectively; p less than 0.001. Histological assessments were available for 73% of the patients. At entry, 63% (66 of 104) in the omeprazole group and 60% (56 of 94) in the cimetidine group (ns) had abnormal histology. After the study, the proportions of patients who initially had had abnormal histology but who then progressed to normal were 67% (44 of 66: omeprazole) and 48% (27 of 56: cimetidine) respectively (p less than 0.001). All patients had reflux symptoms at entry. After four weeks, 46% in the omeprazole group and 22% (p less than 0.001) in the cimetidine group were asymptomatic. Diary cards completed for the first two weeks showed that patients treated with omeprazole experienced fewer reflux symptoms by day and night and used fewer antacids. Omeprazole, 20 mg once a day for four to eight weeks, healed a greater proportion of patients with reflux oesophagitis than cimetidine, 1.6 g per day, assessed endoscopically and histologically, and relieved more patients' symptoms.

Cimetidine↗
PubMed1989

The effects of octreotide, soy polysaccharide, codeine and loperamide on nutrient, fluid and electrolyte absorption in the short-bowel syndrome.

Four agents, which could delay intestinal transit, were tested in six short-bowel patients (jejunal length 30-120 cm) on long-term nutritional/electrolyte replacement therapy. Intestinal transit time of a liquid test meal and nutrient, water and sodium absorption were measured during a control study and with each test agent on separate days. Soy polysaccharide tended to increase transit time, but decreased the absorption of water, sodium and nutrients. Codeine phosphate and loperamide caused inconsistent and clinically unimportant changes. Octreotide, a long-acting analogue of somatostatin, delayed transit and increased water, sodium and calorie absorption from the meal. Octreotide appears to have the potential to reduce the need for electrolyte and nutritional supplements in patients with the short-bowel syndrome.

Codeine↗
PubMed1989

Relationships between symptoms, menstrual cycle and orocaecal transit in normal and constipated women.

Because severe constipation is a disorder largely confined to young women, the possibility that menstrually related factors contribute to disturbed gastrointestinal motor function has been raised. It has also been reported that normal menstruating women show changes in upper gut transit between the follicular and luteal phases of the menstrual cycle and that patients with constipation show prolonged transit. We therefore studied relationships between symptom severity and orocaecal transit during the menstrual cycle in a group of 14 constipated women and a series of control groups comprising seven normal menstruating women, five postmenopausal women, and eight normal men, to determine whether phases of the menstrual cycle were associated with alteration in symptoms or transit. A regular menstrual cycle was reported by 13 of the 14 patients (range 26-30 days) and by all the menstruating female volunteers. Seven patients noted variation in constipation during the menstrual cycle, in all cases this comprised an improvement in symptoms just before or during menstruation. No consistent relationship between symptom severity and follicular or luteal phase was noted. Repeated orocaecal transit measurements in the four study groups showed no consistent differences (greater than 0.05) between groups or during the menstrual cycle (mean change weeks 1-4, -10 +/- 20 min). These findings are inconsistent with the hypothesis of a progesterone related effect upon orocaecal transit in either normal or constipated women.

Adult↗
PubMed1989

Perturbation of upper gastrointestinal transit and antroduodenal motility by experimentally applied stress: the role of beta-adrenoreceptor mediated pathways.

A series of three experiments were performed on healthy adult volunteers to investigate the possible role played by beta-adrenoreceptor mediated pathways in the disturbance of human upper intestinal motor function by hand immersion in cold water. In the first experiment, (an extended pilot study on one individual), orocaecal transit of a standard meal was measured on 36 occasions with and without cold water stimulation and with and without a series of alpha and beta blocking drugs. Cold water stimulation consistently delayed transit in this individual, an effect which was attenuated by prior beta-blockade. In a double blind trial of the effect of beta-blocker atenolol v placebo on transit in nine individuals, a consistent reduction in the cold water induced transit delay was observed (p less than 0.01) independent of any direct effect of beta-blockade. In the third experiment seven individuals underwent repeated studies of antroduodenal pressure activity comparing the effects of cold and warm water stimulation with and without beta blockade to determine whether the observed transit effect could be related to an action on gastrointestinal motility. Cold water stimulation reduced antroduodenal motility, but no consistent effects of previous beta blockade were noted. These studies indicate the presence of a beta-adrenoreceptor mediated pathway in the cold water induced delay of orocaecal transit but not in the inhibition of gastroduodenal motility. Further studies are indicated to determine the site and mode of action of this transit effect more precisely.

Adolescent↗
PubMed1989

Energy absorption as a measure of intestinal failure in the short bowel syndrome.

Energy absorption from a liquid test meal, intestinal transit rate and water and sodium output over a six hour period were measured in five patients with an ileostomy and 12 patients with the short bowel syndrome, five of whom were on longterm parenteral nutrition. The proportion of total energy absorbed was greatest in the ileostomists (median 87%, range 82-92%), less in short bowel patients not on parenteral nutrition (median 67%, range 59-78%, p less than 0.01) and least in the short bowel group who needed it (median 27%, range 2-63%, p less than 0.01). Transit rate was more rapid in the short bowel patients compared with the ileostomists. A close correlation was observed between percentage energy absorption and the dry weight of the stools/stoma effluent collected during the six hour test period (r = -0.99, p less than 0.001). This simple non-invasive test quantitates the degree of intestinal failure and may be of practical help in management.

Adolescent↗
PubMed1989

Motor responses of the upper esophageal sphincter and body to intraluminal acid.

1. It is known that contraction of the upper esophageal sphincter (UES) and secondary peristalsis protect the airway and clear the esophagus of refluxed gastric contents. However, the exact nature of the stimulus and the role of acid remain controversial. 2. Secondary peristalsis and UES responses were measured following the intraluminal infusion of 0.1 N hydrochloric acid and equiosmolar NaCl solutions in seven normal volunteers. The protocol consisted of three phases: infusion of increasing volumes (1, 3, 5 and 7 ml per min), infusion of a given volume (7 ml per min) at different stimulation sites and balloon distension. 3. At the proximal esophagus the UES response to both solutions was similar, rising from a basal resting pressure of 30 mmHg to 70 mmHg for both HCl (range 60-85 mmHg) and NaCl (55-85 mmHg). The magnitude of the response decreased as the distance from the UES increased. The level of response decreased to 40 mmHg for both NaCl and HCl (range 30-60 mmHg) at the distal esophagus. These responses were also volume dependent. When the solutions were infused at 7 ml/min into either the proximal or distal esophagus, the sphincter pressure increased with increased volume to 65 mmHg for HCl (range 50-85 mmHg) and 60 mmHg for NaCl (range 50-80 mmHg). Secondary peristalsis was also induced by the two solutions. The level of response again decreased as the distance from the UES increased. This response was also volume dependent. Esophageal distension by a balloon positioned 10 cm below the sphincter induced secondary peristalsis and sphincter response identical to those induced by the infusion of fluid. 4. These results indicate that the principal stimulus for recruitment of the esophageal motor clearance mechanism is intraluminal distension and not necessarily the pressure of intraluminal acid.

Adult↗
PubMed1988

Functional relationships between cricopharyngeal sphincter and oesophageal body in response to graded intraluminal distension.

Responses of the cricopharyngeal sphincter to graded intraluminal distension were studied in order to determine its response threshold and to define the functional relationship between the sphincter and oesophageal body. Nine normal subjects underwent manometric study using a multilumen tube with an attached inflatable balloon sited 10 cm below the sphincter. Sphincteric and oesophageal motor responses to six graded balloon inflations were recorded in each subject. The sphincter responded to distension with increasing rise in pressure, from a median value of 42.5 mmHg at lowest levels of distension to 95 mmHg at maximal tolerated distension. Non-swallow related contractile activity was stimulated in the oesophageal body proximal to the distension and increased in quantity as inflation progressed. Distal propagation of this secondary activity was progressively inhibited with increasing distension. These interrelated changes thus show the normal upper oesophageal clearance responses to intraluminal distension. It is suggested that their more widespread application, in addition to standard manometric techniques, might provide a more rational evaluation of those patients suspected to have impaired oesophageal clearance, but in whom standard manometry is non-diagnostic.

Adult↗
PubMed1988

Effects of osmoreceptor stimulation on human duodenal motor activity.

The motor responses of the human duodenum to saline solutions of varying osmolality were examined in order to investigate the possible role played by the upper intestine in the control of gastric efflux of hyperosmolar material. During fasting, delivery of the solutions into the duodenum increased duodenal motor activity and intraduodenal pressure, the magnitude of the response increasing with osmolality. At the highest osmolalities, a regular duodenal motor pattern was induced in some individuals which was indistinguishable from fasting phase III activity. After feeding, hyperosmolar saline again increased motor activity. In addition, the transit of an intraduodenal marker to the caecum was accelerated. These findings support the concept that the duodenum is both sensitive and responsive to its intraluminal content. The motor responses additionally appear to function to clear excessively stimulating intraluminal material from the duodenal lumen and may also contribute to the 'postpyloric' resistance which is known to exert control of normal gastric emptying.

Adult↗
PubMed1988

Effect of codeine and loperamide on upper intestinal transit and absorption in normal subjects and patients with postvagotomy diarrhoea.

Patients with chronic severe diarrhoea after truncal vagotomy and pyloroplasty are often difficult to treat using conventional antidiarrhoeal drugs and remain severely disabled. We examined the effect of two drugs, codeine phosphate and loperamide, on upper intestinal transit and carbohydrate absorption, measured non-invasively by serial exhaled breath hydrogen monitoring, in patients with postvagotomy diarrhoea who had previously failed to gain relief from drug therapy. Orocaecal transit was consistently faster in these patients than a group of controls and was associated with malabsorption of glucose. Codeine phosphate 60 mg significantly delayed transit in patients and controls and was associated with a reduction in glucose malabsorption and improvement in symptoms. Loperamide also delayed transit and improved symptoms, but the doses required for this effect (12-24 mg) were higher than usually considered necessary in secretory diarrhoea. These studies indicate that rapid intestinal nutrient transit and associated malabsorption is a factor in the development of diarrhoea postvagotomy and that symptomatic relief can be achieved in most patients by more rational use of existing drugs.

Adult↗
PubMed1988

Studies of the oesophageal clearance responses to intraluminal acid.

Contraction of the upper oesophageal sphincter combined with secondary peristalsis clears the oesophagus of refluxed gastric contents and protects the trachea, but the nature of these reflex stimuli remains controversial. Secondary peristaltic and sphincteric responses were measured during intraluminal infusion of 0.1 N hydrochloric acid and equiosmolar saline solutions in seven normal volunteers. Responses to a single volume infused at varying sites in the oesophagus and to progressively increasing volumes of test solution were measured. In addition oesophageal responses to similar degrees of distension induced by inflation of an intraluminal balloon were also recorded. The sphincteric responses to both stimuli were similar, decreasing in value with distance from the sphincter from values of 70 (68-85) mmHg (median (range] for HCl; and 70 (55-85) mmHg for NaCl at 5 cm below the sphincter to 40 (30-60) mmHg for both HCl and NaCl at 20 cm. As the volume of the solution infused into the proximal oesophagus was increased, the sphincter pressure also rose from a median basal value of 30 (25-50) mmHg to 40 (30-50) mmHg for HCl and NaCl after 1 ml, while after 7 ml infusion, the responses were greater, 65 (45-85) mmHg for HCl, and 60 (45-80) mmHg for NaCl. In the more distal oesophagus, responses were qualitatively similar but quantitatively smaller than proximally, being 30 (25-40) mmHg for HCl and 30 (25-50) mmHg for NaCl following 1 ml and 45 (40-55) mmHg for HCl and NaCl after 7 ml. Secondary peristalsis was also induced equally by both solutions and varied with volumes infused and site of infusion in a manner similar to the sphincter responses. After a 7 ml/min acid infusion 14 (1- 40) secondary contractions/three min were recorded at 5 cm and eight (2 - 18)/three min were recorded at 20 cm. Values for saline were similar, 13 (1- 38)/three min at 5 cm and eight (4 - 25)/three min at 20 cm. Oesophageal distension by a balloon positioned 10 cm below the sphincter induced identical clearance responses to those seen after similar volumes of either acid or saline infused at the same site. These results suggest that the principal stimulus for upper oesophageal clearance is intraluminal distension and do not support the idea that the oesophagus is pH sensitive.

Adult↗
PubMed1988

Dynamic scanning defines a colonic defect in severe idiopathic constipation.

A technique is described in which a chemical stimulus applied to the mucosa of the right colon is used to assess colonic motor function. Peroral intubation of the right colon was achieved using a fine polyvinylchloride (PVC) tube. Bisacodyl was used to initiate colonic motor activity, and colonic transit was monitored using 99mTc-DPTA and a gamma camera. In normal subjects there was rapid movement of the radiopharmaceutical from the right colon to the rectum. In patients with severe idiopathic constipation, a spectrum of colonic abnormality was observed from slow transit involving the rectum and sigmoid only to slow transit involving the whole colon. The hepatic flexure to rectum transit time for the 'head of the isotope column' in normals ranged from 1-10 minutes (mean 5.3 minutes), whereas in patients the transit time was 14-25 minutes in four patients and radioisotope did not reach the rectum by two hours in three other patients (controls v patients, p less than 0.01). Patients also showed relatively impaired transport of the isotope 'mass'. This technique has shown that the normal colon is capable of rapid effective transport in response to a standard stimulus, and that patients with severe idiopathic constipation have a definable colonic motor disorder.

Adult↗
PubMed1987

Motor responses of the oesophagus to intraluminal distension in normal subjects and patients with oesophageal clearance disorders.

Oesophageal motor responses to intraluminal distension were studied manometrically in 16 healthy volunteers and in nine patients with disordered swallowing, who had prolonged oesophageal clearance without structural abnormality. In the normal subjects distension was associated with an increased number of secondary contractions above the balloon, decrease of all contractile activity below the balloon and was accompanied by an aborally propulsive force which occurred independently of the perception of discomfort. Cholinergic blockade abolished the proximal distension induced contractile response, but did not affect primary peristalsis. Despite normal sensory thresholds, proximal excitatory responses to distension were absent in six and distal inhibition was absent in seven patients. These results show that the normal human oesophagus responds to distension with a proximal enhancement of propulsive motor activity, mediated through a cholinergic pathway. This may be defective in some patients with disordered oesophageal transit. Investigation of the motor responses to intraluminal distension may thus be a useful adjunct to standard manometry for studying patients with suspected oesophageal clearance dysfunction and might allow identification of disordered enteric nervous control.

Adult↗
PubMed1987

Motor responses of the small intestine to intraluminal distension in normal volunteers and a patient with visceral neuropathy.

The motor responses of the small intestine to intraluminal distension were studied proximal and distal to an inflatable balloon in 13 normal volunteers. During fasting, distension rapidly induced a persistent localised inhibition of distal contractile activity with a small proximal increase. Proximally, phase III activity was unaffected during distension but its propagation across and appearance below the balloon was inhibited. Upon deflating the balloon a normal motor pattern rapidly returned. Similar changes were observed during distension in the fed state. The changes in the motor pattern resemble those of the intrinsically mediated 'peristaltic reflex', studied in animals, and suggest that in man the response to balloon distension may also be mediated through an intrinsic mechanism. A patient with a visceral neuropathy, studied in a similar manner, had no inhibition of distal motor activity during distension, suggesting a functional defect of the enteric nerves. Further observations of the motor responses to distension in similar patients seem indicated to determine the usefulness of this technique for evaluating enteric nervous system function when an abnormality is suspected.

Adult↗