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Biomedical subjects

N W Read

Publications and source records attributed to N W Read.

At least 91 records · Page 5Linked to original sources
PubMed1993

The effect of feeding xanthan gum on colonic function in man: correlation with in vitro determinants of bacterial breakdown.

Xanthan gum (15 g/d) was given for 10 d to eighteen normal volunteers. In vivo measurements of stool output, transit time, frequency of defaecation and flatulence were compared with a preceding control period of 10 d. At the end of the control and test periods fresh faecal homogenate from each subject was anaerobically incubated with xanthan gum and control solutions to assess the ability of the bacteria to break down the gum. Xanthan gum was found to be a highly efficient laxative agent causing significant increases in stool output (P < 0.01), frequency of defaecation (P < 0.05) and flatulence (P < 0.01) whilst having variable effects on transit time. Before feeding xanthan gum, faecal samples from twelve of the eighteen subjects could reduce the viscosity of the gum in vitro. This rose to sixteen of the eighteen with significantly greater amounts (P < 0.05) of hydrogen and short-chain fatty acids also being produced, indicating bacterial adaptation in the presence of the substrate. Correlations between the in vivo and in vitro findings did not substantiate claims that the in vivo effect of a given polysaccharide can be predicted from its fermentation characteristics in vitro.

Adult↗
PubMed1993

Reduction of rectal sensitivity and post-prandial motility by granisetron, a 5 HT3-receptor antagonist, in patients with irritable bowel syndrome.

The effect of granisetron, a specific 5-hydroxytryptamine 3-receptor antagonist, on the anorectal responses to rectal distension and a 1000-calorie meal was assessed in 12 patients with irritable bowel syndrome. Each patient was studied on three occasions, receiving intravenously either 40 mcg/kg granisetron, 160 mcg/kg granisetron or normal saline. Granisetron caused a dose-dependent reduction in rectal sensitivity, manifested by an increase in the threshold volumes at which the sensations of gas, desire to defecate, urgency and discomfort were perceived. This reached significance for all sensations at the higher dose level (P < 0.01). No significant changes in anal pressures, rectal compliance or distension-induced motor activity occurred following drug administration. A dose-dependent reduction in post-prandial motility was observed following intravenous granisetron and this was highly significant at 160 mcg/kg (P = 0.005). These results suggest that the 5 hydroxytryptamine receptor antagonists may have a therapeutic role in patients with irritable bowel syndrome.

Adult↗
PubMed1993

Granisetron and ondansetron: effects on the ileal brake mechanism in the rat.

Studies were carried out on 20 male adult rats to investigate how the action of the selective 5-HT3-receptor antagonists, granisetron and ondansetron, influence gastrointestinal transit under control conditions and when stomach-to-caecum transit was delayed by ileal infusion of lipid. Stomach-to-caecum transit time (SCTT) was measured using environmental hydrogen analysis. Subcutaneous administration of granisetron (BRL 43694, 40, 80 or 150 micrograms kg-1) significantly delayed the passage of the head of the baked bean meal through the stomach and the small intestine under control conditions (P < 0.05). Similarly, subcutaneous administration of ondansetron (GR 38032F, 80 or 150 micrograms kg-1) delayed control SCTT of the head of the meal but this did not reach statistical significance. In contrast, granisetron significantly reversed the delay in SCTT induced by ileal infusion of lipid at 40 (P < 0.001), 80 (P < 0.01) and 150 micrograms kg-1 (P < 0.05). Ondansetron also reversed the lipid-induced delay at 40 (P < 0.01), 80 (P < 0.001) and 150 micrograms kg-1 (P < 0.001). These apparently conflicting results may be rationalized by postulating the presence of 5-HT3 receptors on afferent nerves which, when inhibited by the specific antagonists, initiate reflexes that both accelerate and delay transit.

Animals↗
PubMed1993

The effect of the cholecystokinin antagonist devazepide (L364718) on the ileal brake mechanism in the rat.

Studies were carried out on 28 male adult rats to investigate whether the selective cholecystokinin-receptor antagonist devazepide influences gastrointestinal transit under control conditions and when it is delayed by ileal infusion of lipid. Stomach-to-caecum transit time of the head of the test meal was measured using environmental hydrogen analysis and the distribution of the meal was assessed using the radiolabelled meal technique. Oral administration of devazepide (4 mg kg-1) had no significant effect on transit time of the head of the baked bean test meal under control conditions, but significantly reversed the delay in transit time induced by ileal infusion of lipid (P < 0.01). Studying the distribution of the meal showed that Intralipid delayed transit time by delaying both gastric emptying (P < 0.01) and small bowel transit (P < 0.05). Devazepide did not alter the control distribution of the meal during ileal saline infusion, but during ileal infusion of lipid, devazepide further delayed gastric emptying (P < 0.01); the geometric centre of the meal was situated more proximally in the gastrointestinal tract (P < 0.05), but there was more of the meal in the colon (P < 0.01). The latter is compatible with the early rise in environmental hydrogen during devazepide administration and ileal lipid infusion and suggests that peripheral cholecystokinin receptors may modulate or mediate the delay in small bowel transit induced by ileal lipid. However, the data also suggest that mechanisms other than those involving cholecystokinin play a dominant role in the regulation of postprandial and lipid-delayed gastric emptying of a meal.

Animals↗
PubMed1993

Effect of food and anti-cholinergic drugs on the pattern of rectosigmoid contractions.

The colonic response to a meal is often used to test the effect of drugs on colonic motility, but this test is hindered by its inconsistency. This study has used multiple manometric sensors situated in the rectosigmoid region to investigate whether recording of the site and type of contraction offers a clear discrimination of the colonic response to a meal and the effect of drugs. Two studies were carried out on 16 healthy volunteers. Before the meal, rectosigmoid motility consisted mainly of isolated contractions occurring in a single manometric channel. The motility index increased in every subject after the meal (p < 0.05), but this increase entirely consisted of a massive increase in contractions occurring simultaneously in three or more manometric channels (multiple channel contractions), the number increasing from 9 per hour preprandially to 57 per hour (p < 0.01). There was a concomitant decrease in the number of the single channel contractions from 65 to 56 per hour. In a second study an infusion of an antispasmodic drug, mebeverine hydrochloride, into the sigmoid colon of healthy volunteers stopped the postprandial increase in the multiple channel contractions and prevented the significant rise in the motility index. The decrease in single channel contractions was unaffected. These results show that the colonic response to a meal consists of a change in the pattern of rectosigmoid contractions and suggest that multiple channel contractions may be a more sensitive indicator of the effect of a meal on the rectosigmoid colon than the motility index.

Adult↗
PubMed1993

Acid, motility, and ulcers: a comparison of cisapride with placebo in the prevention of duodenal ulcer relapse.

In a single centre double blind study of 66 patients, the value of cisapride (10 mg twice daily) was compared with placebo in the prevention of duodenal ulcer relapse. Patients who remained ulcer free attended for clinical review every two months and had a mandatory endoscopy at 0, 4, 8, and 12 months or if symptoms suggestive of ulcer recurrence developed. The 12 month crude relapse rates (that underestimate the probability of ulcer recurrence) showed that cisapride was superior to placebo (34% (11/32) relapsed on cisapride v 68% (23/34) on placebo, p = 0.007). This finding was confirmed using lifetable analysis, with a 35% reduction (95% confidence intervals 10-59%, p < 0.05) in the proportion of ulcer relapses in patients who had received cisapride compared with those treated with placebo. These results are similar to those reported in maintenance trials of H2 receptor antagonists analysed by the same method. Drug related adverse clinical events were mainly trivial, but led to three patients on cisapride and one on placebo withdrawing from the trial.

Adolescent↗
PubMed1993

The effect of liquid fibre on gastric emptying in the rat and humans and the distribution of small intestinal contents in the rat.

A combination of the polysaccharide ethyl-hydroxyethyl-cellulose (EHEC) and the surfactant sodium-dodecylsulphate (SDS) has the extraordinary physical property of being liquid at room temperature but gelling firmly at 37 degrees C. It has been named 'liquid fibre' and its effect on gastric emptying has been tested in rats and humans, as well as its effect on intestinal distribution in rats. Rats were gavaged with 5 ml of radiolabelled liquid fibre, SDS in water, or water control. Subgroups were killed after 25, 50, 100, 200, and 300 minutes, the gut removed, and the distribution of radioactivity measured scintigraphically. Liquid fibre gelled in the stomach and spread exponentially down the small intestine before 25 minutes. This distribution was maintained for 200 minutes after which the stomach began to empty again. In the human study, 10 healthy men drank 250 ml liquid fibre and placebo labelled with 1.85 MBq technetium tin colloid on separate occasions. Gastric emptying was measured by gamma-camera. Half emptying time significantly increased from 17.7 to 55.8 minutes (means, p < 0.05). The time for 10% to empty (which includes any lag time) increased from 7.0 to 19.4 minutes (p < 0.05). Average emptying rate decreased from 4.49%/min for placebo to 1.60%/min for liquid fibre (p < 0.01). The dramatic delay in gastric emptying suggests liquid fibre may have clinical applications while its liquid formulation should improve acceptability.

Adult↗
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

The effect of an opiate receptor antagonist on the ileal brake mechanism in the rat.

Studies investigated the effect of the opiate antagonist naloxone (10 mg/kg) on stomach to caecum transit (SCTT) during ileal infusion of saline or Intralipid. SCTT of the head of the meal was measured by hydrogen analysis and meal distribution by the radiolabelled meal technique. Intralipid delayed SCTT by delaying both gastric emptying (p < 0.01) and small bowel transit. Naloxone did not affect SCTT during ileal saline infusion, but produced a distal shift (p < 0.05) in the geometric centre of the meal and increased radioactivity in the caecum (p < 0.001) 100 min after gavage. Naloxone abolished the delayed SCTT of the meal induced by ileal lipid infusion, with an associated increase in radioactivity in the caecum at 200 min (p < 0.01), although the geometric centre was shifted proximally within the intestine (p < 0.01). The results suggest that the ileal brake is mediated in part by endogenous opiate pathways.

Animals↗
PubMed1993

In vitro effects of sennoside on contractile activity and fluid flow in the perfused large intestine of the rat.

The effect of sodium rhein on contractile activity and fluid flow in the rat complete large intestine was studied in vitro. Contractile activity was recorded using serosal strain gauges and volume transducers recorded distal fluid flow from the segment. Luminal sodium rhein (1 mM) produced a protracted increase in caecal activity yet increased colonic contractility transiently. Fluid flow from the preparation was increased and the number of propagated complexes was elevated after the initial 10 min of exposure. The effect did not appear to be related directly to dose. Sodium rhein (0.1 mM) did not significantly stimulate contractility and a higher dose (5 mM) only produced a transient effect on propagated contractions. However, this dose had the effect of significantly reducing activity when the rhein was replaced by normal buffer. The data suggest that the action of sodium rhein is subtle; after an initial excitation, the glycoside shifts the pattern of motor activity in favour of propulsion at the expense of segmentation. The large intestine is more able, therefore, to expel luminal contents in a caudal direction following the addition of this anthraquinone laxative.

Animals↗
PubMed1993

Preliminary studies on the gastrointestinal responses to fatty meals in obese people.

Studies were carried out on eight obese (BMI 30-34.6 kg/m2) and seven age and sex-matched normal weight volunteers (BMI 20-25 kg/m2) to investigate the gastric emptying, mouth to caecum transit time (MCTT), plasma cholecystokinin (CCK) and sensory responses to high (30 g margarine; 1327 kJ (317 kcal)) and low (301 kJ (72 kcal)) fat soups. Gastric emptying was measured by gamma scintigraphy, MCTT was measured by the breath hydrogen technique, plasma CCK was measured using a bioassay technique and subjective sensations were recorded on visual analogue scales. The high fat meal emptied more slowly than the low fat meal in both the normal subjects (t1/2 = 86.3 +/- 9.2 vs. 36.7 +/- 2.8 min) but there were no differences in the emptying of either meal between the two groups of subjects. Increasing the fat content of the meal did not affect the mouth to caecum transit time (MCTT) in either group, nor were there differences between the groups in MCTT (180 +/- 23 vs. 188 +/- 35 min, normal vs. obese MCTT after low fat soup; 228 +/- 17 vs. 227 +/- 29 min, normal vs. obese MCTT after high fat soup). Despite similar rates of gastric emptying, the obese group showed a higher CCK production following the high fat meal than the normal weight group (540.4 +/- 65.9 vs. 336.9 +/- 51.4 pmol.min, 2 h integrated CCK production, obese vs. normal; P < 0.05). The obese group also reported feeling less hungry throughout the study than the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Haemorrhoids are associated not with hypertrophy of the internal anal sphincter, but with hypertension of the anal cushions.

A combined manometric and ultrasonographic study of the internal anal sphincter was carried out in 20 patients with haemorrhoids and 20 age-matched normal controls. Mean(s.e.m.) basal anal pressure was significantly higher in patients than in controls, 62(4) versus 45(6) cmH2O (P less than 0.05), although there were no significant differences in mean maximum basal and squeeze pressures. During rectal distension 90 per cent of patients showed no reduction in anal pressure in the outermost anal channel, although the internal sphincter electromyogram was suppressed and the external sphincter electromyogram did not necessarily increase above baseline. The mean(s.e.m.) maximum residual pressure was significantly higher in patients, 70(6) versus 45(6) cmH2O (P less than 0.05). Direct pressure measurement in anal cushions exhibited abnormally high median pressure in patients compared with controls, 35 versus 10 cmH2O (P less than 0.001). Pressures recorded during coughing and straining were also significantly higher in patients than in controls (P less than 0.001). Ultrasonographic study of the anal canal revealed a clear image of the internal sphincter, the thickness of which could easily be measured. The mean(s.e.m.) thickness of the sphincter was not significantly different, 2.3(0.2) versus 2.1(0.1) mm, between patients with haemorrhoids and controls (P = 0.18). The absence of any significant differences in the internal sphincter thickness between normal subjects and patients with haemorrhoids suggests that the high anal pressure in patients with haemorrhoids is of vascular origin.

Adult↗
PubMed1992

The effect of ingestion of guar gum on ileostomy effluent.

Randomized, paired studies were carried out on five healthy volunteers equipped with terminal ileostomies to investigate the effect of incorporating 15 g of the viscous polysaccharide guar gum in the normal diet on the volume, weight, composition and physical properties of ileostomy effluent. Subjects ate an identical diet during two 5 d study periods, which were separated by 2 d. Outputs of fat, protein, sodium, potassium, dry weight and water were all increased during guar gum administration, but outputs of carbohydrate, calcium and phosphorus were not significantly altered. Mouth-to-stoma transit was not significantly affected and, surprisingly, the viscosity of the ileostomy effluent was reduced by guar gum. These results show that it is not always possible to predict what will happen to small intestinal function when guar gum is added to the diet from experiments carried out when guar gum is administered alone or with glucose. While our findings show that guar gum will reduce fat absorption, the mechanisms involved are more sophisticated than hitherto envisaged.

Aged↗
PubMed1992

Role of gastrointestinal factors in hunger and satiety in man.

There is, we feel, a strong case to be made for a major influence of gastrointestinal factors in the control of eating behaviour in humans. Moreover, the findings suggest that satiety and hunger are controlled by different gastrointestinal mechanisms. Gastric distension is perhaps the most important factor that stops people eating, but a true feeling of satiety also requires the presence of nutrients in the small intestine. Hunger appears to be little influenced by the amount of food in the stomach and appears to be more dependent on the nutrient load in the small intestine. I do not mean by this to suggest that the gastrointestinal mechanisms are the only mechanisms controlling eating behaviour in humans or even the most important. Nevertheless they constitute an important and fundamental control system that links with the post-absorptive mechanisms and a plethora of social and conditioning factors to influence what we eat.

Digestive System Physiological Phenomena↗
PubMed1992

Effect of sumatriptan, a new selective 5HT1-like agonist, on liquid gastric emptying in man.

Paired studies were carried out on 12 healthy male subjects to compare the effect of intravenous doses of the 5-HT1-like agonist sumatriptan (GR43175; 3 mg), 10 mg metoclopramide and saline control on the rate of gastric emptying of a radiolabelled liquid test-meal. Intravenous administration of metoclopramide accelerated gastric emptying by decreasing the lag period, while intravenous administration of sumatriptan delayed gastric emptying by increasing the lag period. The observation that sumatriptan causes a delay in gastric emptying in normal healthy volunteers, but relieves nausea and vomiting during migraine attacks, suggests that sumatriptan may be acting via a central mechanism to relieve symptoms of nausea and vomiting associated with migraine.

Adult↗
PubMed1992

The effect of adrenoceptor antagonists on the ileal brake mechanism in the rat.

1. Studies were carried out in the rat to investigate the effect of adrenoceptor antagonists on stomach to caecum transit time under control conditions and during ileal infusion of Intralipid. Stomach to caecum transit time (SCTT) of the head of the meal was measured by use of environmental hydrogen analysis and the distribution of the meal was assessed by a scintigraphic technique. 2. Four adrenoceptor antagonists were used in these studies, the alpha 1 antagonist prazosin, the alpha 2 antagonist, idazoxan, the beta 1 antagonist atenolol and the beta 2 antagonist ICI 118551. 3. None of the antagonists affected SCTT of the head of the meal during ileal infusion of saline. However, the alpha 1 and beta 1 antagonists significantly reversed (P less than 0.05) the delay in SCTT induced by ileal infusion of Intralipid whereas the alpha 2 antagonist, idazoxan, potentiated this delay (P less than 0.05). 4. Study of the distribution of the radiolabelled meal showed that the Intralipid delayed SCTT by slowing both gastric emptying (P less than 0.05) and small bowel transit (P less than 0.05). 5. Prazosin delayed gastric emptying under control conditions (P less than 0.001) but did not alter significantly the effect of ileal lipid on the distribution of the meal, 100 min or 200 min after gavage.6. The meal distribution was more compatible with the hydrogen analysis after administration of the ,beta-adrenoceptor antagonists. The reversal of the lipid-induced delay in SCTT caused by atenolol was associated with more radioactivity in the large intestine 200min after the gavage. ICI 118551 had no significant effects on either the distribution of the meal or the SCTT of the head of the meal.7. In conclusion, the data confirm that the sympathetic nervous system normally modulates or mediates the mechanisms that influence gastrointestinal transit in the rat and suggest that these mechanisms may be involved in the ileal brake effect. Nevertheless the data also suggest that simple measurement of the transit of the head of the meal by use of environmental hydrogen analysis may sometimes give a misleading impression of the action of drugs on gastrointestinal transit of the bulk of a test meal.

Adrenergic Antagonists↗
PubMed1992

Anorectal function in patients with complete supraconal spinal cord lesions.

Anorectal manometry and sphincter electromyography were performed in 23 patients with complete supraconal traumatic spinal injuries and 30 age and sex matched control subjects. Basal pressures in the spinal group were similar to those in normal subjects but conscious control of sphincter activity was abolished in all spinal patients. Discriminant rectal sensation was also abolished during rectal distension, but 40% of patients experienced a dull pelvic ache at maximum levels of distension. Phasic rectal contraction and anal relaxation were present but exaggerated and induced at lower distending volumes than in normal subjects. The configuration of the rectal pressure/volume relationship was linear in patients compared with a reversed 'S' shape in normal subjects. The external anal sphincter response to rectal distension was noticeably attenuated, reinforcing the view that this spinal reflex is heavily modulated by supraspinal centres under normal circumstances. The external anal sphincter response to increases in abdominal pressure was also attenuated, and the anal pressures were strongly correlated with the level of the lesion and the abdominal pressure the patient could generate. No spinal patient showed a decrease in external anal sphincter activity during straining 'as if to defecate.' The exaggerated anorectal smooth muscle responses to rectal distension and the attenuated external sphincter response explain why patients with complete supraconal spinal lesions experience uncontrollable reflex defecation, while the persistance of external and sphincter contraction and the absence of any external anal sphincter relaxation during straining 'as if to defecate' might explain the difficulty that these patients have in consciously expelling rectal contents.

Adolescent↗