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Biomedical subjects

N W Read

Publications and source records attributed to N W Read.

At least 235 records · Page 13Linked to original sources

Metoclopramide reduces carbohydrate absorption in man.

The effect of metoclopramide (20 mg p.o) on the times taken for a radiolabelled liquid starch meal to empty from the stomach and to reach the ileum (230 cm from the mouth), the ileal flow rates and the degree of carbohydrate absorption were studied in five normal male volunteers, intubated with a four lumen intestinal tube. Administration of metoclopramide significantly reduced the time taken for delivery of 50% and 80% of the meal to the ileal aspiration site, but had no significant effect on the half time for gastric emptying. Administration of metoclopramide did not affect the average flow rate or the total postprandial volume, which passed the ileal aspiration site. Administration of metoclopramide reduced carbohydrate absorption in every subject by between 8 and 30%. This study is consistent with the hypothesis that metoclopramide may reduce the degree of absorption in the human small intestine by decreasing the contact time between food and small intestinal epithelium, though it could also act by reducing the area of mucosa in contact with nutrients.

Adolescent↗

Interpretation of the breath hydrogen profile obtained after ingesting a solid meal containing unabsorbable carbohydrate.

The extent to which monitoring breath hydrogen excretion provides information concerning the entry of the residues of a solid test meal into the colon was investigated in 89 normal subjects, and 11 patients with the irritable bowel syndrome. The profile of breath hydrogen concentration showed an early peak, that occurred soon after ingesting the test meal in 89% subjects. This was followed by a later more prolonged rise in breath hydrogen concentration. The early peak occurred well before a radioactive marker, incorporated in the test meal, reached the caecum and the data suggest it was predominantly caused by the emptying of the remnants of the previous meal from the ileum into the colon. This hypothesis was supported by direct measurements of the rate of delivery of ileostomy effluent in 12 subjects with terminal ileostomies. Fermentation of carbohydrate in the mouth may, however, contribute to the initial peak, but this contribution may be avoided by collecting gas samples from the nares. The secondary rise in breath hydrogen excretion was closely correlated with the arrival of the radioactive marker in the caecum (r = 0.91), p less than 0.001), though the time, at which the secondary peak of breath hydrogen excretion occurred was poorly correlated with the time that all the radioactive test meal had entered the colon. When lactulose was infused directly into the colon, as little as 0.5 g produced a discernible hydrogen response, which occurred within two minutes of the infusion. Increasing the rate of colonic infusion of a 50 ml solution of 10% lactulose from 0.02 to 0.15 g/min in five subjects significantly increased the breath hydrogen concentration. At infusion rates below 0.075 g lactulose/minute, the peak breath hydrogen response preceded the end ot the infusion, while at higher rates of infusion, the peak hydrogen response occurred after the end of the infusion. Although these results confirmed that monitoring breath hydrogen concentration usefully signalled the time taken for a meal containing unabsorbed carbohydrate to reach the colon, it did not reliably indicate the time when all of the meal had entered the colon. Finally, the use of the maximum increase in breath hydrogen concentration as an index of the degree of carbohydrate malabsorption assumes uniform rates of entry into the colon.

Absorption↗

Vagal control of fluid transport, transmural potential difference, and motility in the ferret jejunum.

The role of the vagus nerve in the control of intestinal transport was investigated in the ferret jejunum in vivo. Fluid transport was measured in an isolated 10-cm segment of jejunum by means of a single-pass perfusion technique with radioactive markers introduced into the perfusion fluid and the bloodstream of the animal. Transmural potential difference (PD) and intraluminal pressure in the perfused jejunal loop were also monitored. Vagal stimulation (20 Hz, 20 V, and 0.5 ms for 1 min) resulted in jejunal fluid movement in the direction of secretion, a rise in transmural PD, and an increase in jejunal contractile activity. Similar changes were induced by close intra-arterial injection of acetylcholine (20 micrograms X kg-1). The contractile response to vagal stimulation was abolished by atropine. Moreover, atropine did not block the changes in fluid transport and transmural PD that were induced by vagal stimulation, although the transmural PD response was reduced. The results suggest that vagal stimulation induces intestinal secretion accompanied by a rise in transmural PD; the events are mediated at least in part by a noncholinergic transmitter as yet undetermined.

Acetylcholine↗

Differences in anal function in patients with incontinence to solids and in patients with incontinence to liquids.

Manometric radiological and neurophysiological measurements of the anal sphincter were carried out in 19 female patients who were incontinent to liquid faeces only, 15 female patients who exhibited incontinence to solid and liquid faeces and 18 normal female controls. Both groups of patients had abnormally obtuse anorectal angulation and perineal descent, a weak and easily inhibited sphincter tone and similar degrees of neuropathy during electromyography. However, patients who were incontinent to solids and liquids exhibited lower squeeze pressures during standard manometry and lower peak pressures during saline infusion than patients who were only incontinent to liquids. These findings suggest that it is the additional weakness of the external sphincter that renders patients incontinent to solids as well as liquids.

Adult↗

Role of loperamide and placebo in management of irritable bowel syndrome (IBS).

Symptom scores, stool data, and the transit of a standard, solid meal were measured in 28 patients with irritable bowel syndrome (IBS) during baseline conditions and after five weeks of treatment with placebo and loperamide, given as a flexible dosage regime in the form of a double-blind, cross-over trial. All patients had undergone a comprehensive series of diagnostic investigations and had failed to respond to dietary supplementation with coarse wheat bran (10-30 g daily). Loperamide treatment accelerated gastric emptying, compared with placebo (1.2 +/- 0.1 vs 1.5 +/- 0.1 hr; P less than 0.001) and delayed both small bowel (6.2 +/- 0.3 vs 4.3 +/- 0.3 hr; P less than 0.001) and whole gut transit (56 +/- 5 vs 42 +/- 4 hr; P less than 0.01). Eighteen patients said they felt better taking loperamide compared with placebo and, at follow up, 15 of these patients remained satisfied with the effects of the drug. Most symptoms improved significantly on placebo compared with the baseline period, but three of these [diarrhea (P less than 0.01), urgency (P less than 0.01) and borborygmi (P less than 0.05)] showed a further significant improvement on loperamide. Improvement in diarrhea was not associated with any change in stool weight but was associated with reductions in stool frequency (P less than 0.001), passage of unformed stools (P less than 0.01), and incidence of urgency (P less than 0.001). Urgency was the only symptom that was significantly more common in the success group, compared with the group who did not feel better on loperamide.

Adult↗

Effect of painless rectal distension on gastrointestinal transit of solid meal.

The effect of painless intermittent rectal distension on the rate at which a standard meal passes through the stomach and small intestine was investigated in normal volunteers using noninvasive techniques. Rectal distension significantly retarded the entry of the head of the meal into the cecum and the emptying of the meal from the stomach, although it had no significant effect on basal gastric acid secretion. After administration of the H2-receptor antagonist, ranitidine, there was no significant effect of rectal distension on gastric emptying, but the delay in small bowel transit time induced by rectal distension remained. These data indicate that events occurring in the rectum may influence the function of more proximal regions of the gut.

Adolescent↗

The mechanism of action of guar gum in improving glucose tolerance in man.

Experiments were carried out in human volunteers to investigate the mechanism by which guar gum improves glucose tolerance. Guar reduced both plasma glucose and insulin responses to an oral glucose load, and delayed gastric emptying. However, there was no correlation between changes in individual blood glucose responses and changes in gastric emptying rates induced by guar. With a steady-state perfusion technique, glucose absorption was found to be significantly reduced during perfusion of the jejunum with solutions containing guar, but returned to control values during subsequent guar-free perfusions. Preperfusing the intestine with guar did not affect electrical measurements of unstirred layer thickness in the human jejunum in vivo. Experiments in vitro established that glucose diffusion out of a guar/glucose mixture was delayed under conditions of constant stirring. We conclude that guar improves glucose tolerance predominantly by reducing glucose absorption in the small intestine. It probably does this by inhibiting the effects of intestinal motility on fluid convection.

Adolescent↗

The effect of ispaghula (Fybogel and Metamucil) and guar gum on glucose tolerance in man.

The effects of incorporating Fybogel (3.5 and 7 g doses), Metamucil (7 g) or guar gum (2.5 and 14.5 g doses) in a drink containing 50 g glucose on plasma glucose, plasma insulin and gastric emptying were studied in thirty-eight normal volunteers. In addition, the effects of Fybogel (7 g) on glucose tolerance, plasma insulin and gastric emptying were measured in fourteen non-insulin-dependent diabetics. Both doses of guar gum significantly lowered plasma glucose and plasma insulin responses to the oral glucose load in normal subjects, although 14.5 g guar gum did not delay the half-time for gastric emptying. Neither Fybogel nor Metamucil had significant effects on plasma glucose responses in normal subjects. In addition, Fybogel (at either dose) had no significant effects on plasma insulin levels, or on gastric emptying in normal subjects or on plasma glucose and insulin responses in diabetic patients. The viscosity of ispaghula solutions ( Fybogel ) was lower than that of guar gum solutions.

Adult↗

Does guar gum improve post-prandial hyperglycaemia in humans by reducing small intestinal contact area?

The possibility that viscous polysaccharides, such as guar gum, could lower post-prandial blood glucose levels in part by restricting carbohydrate solutions to a smaller area of small intestine was investigated in twenty healthy human volunteers. Addition of guar gum (22.5 g/l) delayed the mouth-to-caecum transit time of a hypotonic lactulose drink, but did not affect gastric emptying. When a 250 ml solution containing 50 g glucose was confined to a 550 mm length of intestine by an occluding balloon attached to an intestinal tube, maximum blood glucose response was significantly reduced (P less than 0.05) though only by 0.9 mmol/l. Addition of guar gum (36 g/l) had no effect on the distribution of a radio-labelled glucose drink (250 ml; 200 g glucose/l) in the small intestine, monitored using a gamma camera, although it significantly delayed gastric emptying (t 1/2 (min): guar gum v. control 115 (SE 15) v. 73 (SE 8)). Reduced contact area is unlikely to be one of the mechanisms by which guar gum improves glucose tolerance.

Adult↗

Effect of secoverine and atropine on intestinal secretion and motor activity in the rat small intestine in-vivo.

The actions of secoverine and atropine on bethanechol-induced intestinal secretion, hypermotility and transintestinal potential difference were investigated in the rat jejunum in-vivo. Both secoverine (10(-7) mol kg-1) and atropine (1.2 X 10(-9) mol kg-1) inhibited motility at doses that did not affect secretion or transintestinal potential difference. However, secoverine was a less potent antagonist of all the bethanechol-induced changes than atropine. Increases in transintestinal potential difference were more closely related to production of fluid secretion than to increases in motility.

Animals↗

What is the benefit of coarse wheat bran in patients with irritable bowel syndrome?

The effect of open treatment with coarse wheat bran was compared with response to placebo, given in the form of a double blind, cross over drug trial, in patients with irritable bowel syndrome. Both bran and placebo significantly reduced the severity of most of the symptoms. Constipation was the only symptom that improved significantly with bran, but not with placebo, and was the only symptom that predicted a successful outcome with bran. Diarrhoea did not improve with bran. In fact, stools became less formed in patients presenting with this symptom. The incidence of pain and urgency was significantly more frequent on bran compared with placebo. Compared with a baseline period, bran treatment resulted in an acceleration of whole gut transit time (p less than 0.05) increases in daily stool weight (p less than 0.01) and the proportion of unformed stools (p less than 0.01) but no change in stool frequency. Coarse wheat bran was no better than placebo for most symptoms in irritable bowel syndrome, although its efficacy in constipation was confirmed.

Adult↗

Is raised breath hydrogen related to the pathogenesis of pneumatosis coli?

Clinical and physiological studies were carried out in five patients with pneumatosis coli in order to investigate the origin of the high fasting breath hydrogen concentration in this condition and to determine its possible significance in the pathogenesis of the disease. All five patients excreted abnormally high fasting concentrations of hydrogen in their breath (69 +/- 9 ppm, mean +/- SEM). Moreover, analysis of the contents of the gas filled cysts revealed between 2% and 8% of hydrogen gas. Colonic washout significantly reduced breath hydrogen concentrations to 9 +/- 6 ppm, but did not abolish the cysts. Conversely, deflation of the cysts was achieved with oxygen or antibiotics, though this only reduced breath hydrogen concentrations to about 66% of their original value. After feeding a radiolabelled meal, breath hydrogen concentrations rose before the meal appeared to reach the colon, suggesting overgrowth of anaerobic bacteria in the small intestine. Despite this, 14C glycocholate breath tests were within normal limits. An alternative possibility is that the high levels of hydrogen excreted in the breath may be produced in the intestinal lumen possibly from the fermentation of copious amounts of colonic mucus. Finally, measurement of whole gut transit time and stool weight suggested that patients were constipated despite passing mucus and blood. The relevance of our observations to the pathogenesis of submucosal cysts is unclear, but the data favour the hypothesis that these are produced by invasion of the colonic submucosa with anaerobic bacteria.

Adult↗

The relationships between colonic motility and transport.

The salvage of unabsorbed nutrients, salt and water in the colon requires the integration of functions of bacterial digestion and epithelial transport with motor activity. However, the motor and transport functions of the colon are poorly understood owing to the inaccessibility of that organ. This paper discusses some of the ways in which motor activity may influence colonic absorption and vice versa, using examples taken from studies carried out in the small intestine. In particular, the effect of factors such as convection, transit time, reflex secretion and blood flow are discussed.

Animals↗

Small bowel transit time of food in man: measurement, regulation and possible importance.

Studies on the relevance of scintigraphy and breath hydrogen analysis to the measurement of small bowel transit time are outlined. The main dietary factor influencing small bowel transit time appears to be the level of unabsorbable carbohydrate. The rates of gastric emptying and small bowel transit seem to be largely independent of one another. A weak correlation exists between the time for 50% of a meal to enter the caecum and the contraction frequency of the upper jejunum. Unabsorbed food in the ileum may increase the period over which material remains in the small intestine. Absorption cannot be predicted from a knowledge of transit kinetics alone. Diarrhoea may arise if rapid small bowel transit causes unduly rapid entry of fluid into the colon. In the irritable bowel syndrome, accelerated small bowel transit occurs in patients with diarrhoea.

Biological Transport, Active↗

Effect of infusion of nutrient solutions into the ileum on gastrointestinal transit and plasma levels of neurotensin and enteroglucagon.

The small bowel transit time of 100 ml of lactulose solution infused at the ligament of Treitz was measured by breath hydrogen excretion in paired studies carried out in 43 healthy volunteers during infusion (1.2 ml/min) of equal volumes (100 ml) of isotonic solutions of either fat emulsion (Intralipid, Prosparol, or Calogen), protein hydrolysate, glucose, or saline into either the jejunum (90 cm from the teeth), ileum (205 cm from the teeth), or colon (350 or 400 cm from the teeth). Ileal infusion of Intralipid or protein hydrolysate resulted in significant delays in small bowel transit time (125 +/- 21 min and 71 +/- 11 min, respectively) compared with infusion of saline (50 +/- 3 min; p less than 0.02 and p less than 0.05). These delays were not associated with any significant alteration in plasma levels of neurotensin or enteroglucagon. Small bowel transit time was unaffected by infusion of nutrients into the colon or jejunum, although jejunal infusion of Intralipid increased the plasma levels of enteroglucagon and neurotensin (p less than 0.01 and p less than 0.02, respectively) after the start of lactulose infusion. In a separate series of paired experiments, infusion of Intralipid into the ileum in 5 volunteers significantly delayed the transit of a solid test meal labeled with 25 microCi of 99mTc-sulfur colloid through both the stomach and small intestine. These data support the existence of a mechanism whereby the presence of unabsorbed food in the ileum may enhance absorption by delaying the passage of food through the small intestine.

Adult↗

Relationship between postprandial motor activity in the human small intestine and the gastrointestinal transit of food.

Profiles for gastric emptying and colonic filling were determined in 20 normal volunteers by means of a gamma camera and dedicated minicomputer after ingestion of a radiolabeled solid meal. These were compared with intraluminal pressure activity, recorded simultaneously from three sites (each separated by 50 cm) in the small intestine by infusion manometry. Recordings were continued for at least 8 h or until all the radioactivity appeared in the colon. Colonic filling was approximately linear, occurring at an average rate of 16% of the meal residues per hour. There were significant inverse correlations (p less than 0.01) between the pressure activity in the proximal jejunum during the first 3 h after ingestion and the times taken for 50% and 80% of the meal residues to enter the colon, and direct correlations between total small intestinal pressure activity and the half-time for gastric emptying. Phase III of the interdigestive migrating motor complex appeared between 3 and 9 h after ingestion (when between 15% and 80% of the meal remained in the small intestine), but did not necessarily migrate to the next recording site until much later. The time of appearance of phase III in the proximal jejunum was directly correlated with the half-time for gastric emptying (p less than 0.05) and with the intraluminal pressure activity recorded at that site during the first 3 h after food ingestion (p less than 0.01). The time at which 80% of the meal residues had entered the colon was significantly shorter in 6 subjects, in whom a postprandial activity front appeared to migrate throughout the small bowel, compared with 13 subjects, in whom this did not occur (5.0 +/- 0.5 h vs. 7.0 +/- 0.4 h, p less than 0.01). These studies have shown that gastrointestinal transit of a solid meal is related to both fed and fasted intraluminal pressure activity in the small intestine.

Adult↗

Effect of naloxone on feedback regulation of small bowel transit by fat.

Studies were carried out in 7 healthy male volunteers to investigate whether the delay in small bowel transit time, induced by the infusion of fat emulsions into the human ileum, was mediated by endogenous opioids. The effect of ileal infusion of intralipid on small bowel transit time of a 100-ml solution containing 13.3 g of lactulose was studied during intravenous infusion of either saline or naloxone (20 micrograms/kg X h) in saline. During intravenous infusion of saline, ileal infusion of fat significantly delayed small bowel transit time of the head of the lactulose infusion (ileal intralipid vs. saline; 249 +/- 46 vs. 44 +/- 8 min; mean +/- SEM; p less than 0.01). Intravenous infusion of naloxone, however, abolished the delay in small bowel transit time induced by ileal infusion of intralipid in 5 of 7 subjects (intravenous naloxone; ileal intralipid vs. saline; 89 +/- 26 vs. 46 +/- 8 min; p greater than 0.2). Intravenous naloxone had no effect on small bowel transit time when saline was infused into the ileum. This result suggests that endogenous opioids may be involved in the feedback regulation of small bowel transit by ileal intralipid.

Adult↗