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Biomedical subjects

N W Read

Publications and source records attributed to N W Read.

At least 217 records · Page 12Linked to original sources

Physiological studies in young women with chronic constipation.

Manometric, radiological and neurophysiological investigations were performed on 34 women, aged between 14 and 53, who suffered with chronic constipation refractory to treatment, and on 27 age-matched normal female control subjects. The constipated patients had more difficulty in evacuating simulated stools than control subjects and 13 out of 19 patients tested obstructed defaecation by contracting the external sphincter during straining. The constipated group required a greater degree of rectal distension than control subjects to induce rectal contractions, anal relaxation and a desire to defaecate. Other modalities of rectal sensation were normal in the constipated subjects. Compared with controls, constipated patients had significantly lower anal pressures, an abnormal degree of perineal descent on straining and an obtuse anorectal angulation at rest. These results were compatible with weakness of the pelvic floor and neuropathic damage to the external sphincter. Mouth to anus transit time was abnormally prolonged in 60% of constipated patients, but was within the normal range in the remainder. Anorectal function in patients with slow transit was not significantly different from that in patients with a normal transit time. The mouth to caecum transit time of a standard meal was prolonged in constipated patients irrespective of the duration of the whole gut transit. Gastric emptying was not significantly prolonged.

Adolescent↗

Impairment of defecation in young women with severe constipation.

Anorectal manometry, radiology, and tests of simulated defecation were carried out in 14 severely constipated young women and 29 age-matched controls. The resting anal sphincter pressures were reduced in the patients, but the squeeze pressures, rectoanal inhibitory reflex, and rectal pressures upon balloon distention were all normal. At rest, the anorectal angle was more obtuse in the constipated group, but there was no overall increase in perineal descent in constipated patients compared with controls. The presence of a balloon in the rectum and the onset of pain were perceived in constipated patients at volumes that were not significantly different from those in normal volunteers. Constipated patients, however, required higher rectal volumes to induce the desire to defecate and to stimulate regular rectal contractions. Constipated patients also found it more difficult to pass simulated stools from the rectum than the normal controls and, unlike most normal controls, failed to inhibit their external anal sphincter on attempted defecation. These findings suggest that young women with severe constipation have great difficulty initiating the coordinated set of events that constitute a normal defecation response.

Adolescent↗

Swallowing food without chewing; a simple way to reduce postprandial glycaemia.

1. The degree to which disruption by mastication affects the glycaemic response to four different carbohydrate foods was investigated in healthy human volunteers; each food was eaten by six subjects. 2. Subjects ate meals of sweetcorn, white rice, diced apple or potato on two occasions; on one occasion they chewed the food thoroughly, on the other occasion they swallowed each mouthful without chewing it. 3. When the foods were chewed the postprandial blood glucose levels rose to levels which varied according to the food ingested. 4. Swallowing without chewing reduced the glycaemic response to each food, achieving a similar effect as administration of viscous polysaccharides or 'slow-release' carbohydrates.

Adult↗

The degradation of guar gum by a faecal incubation system.

1. Homogenized and diluted faeces (50 g/l) from one human source were incubated with the complex plant polysaccharide, guar gum, to investigate the degradation of viscous polysaccharides by intestinal bacteria. 2. Incubation of the faecal homogenate with guar gum produced a rapid decrease in viscosity and in pH, accompanied by the release of hydrogen. 3. No changes in viscosity or pH were observed and there was no production of H2 gas when guar gum was incubated with autoclaved faecal homogenate (20 min, 1.03 x 10(5) Pa). 4. A bacteria-free filtrate of faeces was prepared by centrifuging the faecal homogenate (2400 g for 100 min) followed by filtration through a Seitz filter and then a millipore filter (size 0.45 micron). Incubating this with guar gum produced a slow decrease in viscosity, but no significant change in pH and no generation of H2. 5. Our results show that guar gum can be fermented by human colonic bacteria and suggest the possibility of predigestion by extracellular free enzymes.

Bacteria↗

How does dietary lipid lower blood alcohol concentrations?

To determine the mechanism, whereby food lowers blood alcohol concentrations, gastric emptying and blood alcohol profiles were measured in six healthy male volunteers after they had drunk a 200 ml solution of vodka and orange juice containing 0.5 g/kg alcohol. Subjects were studied on two separate occasions during infusion of isosmotic solutions of either Intralipid or saline into the ileum via an intestinal tube. Gastric emptying was significantly delayed by ileal infusion of fat emulsion and the peak blood alcohol concentration was significantly depressed. Similar effects were observed in three subjects when the solutions were infused into the duodenum. These results suggest that the reduction in alcohol absorption by food does not depend on the physical relationship between the alcohol and the food or between the food and the absorbing epithelium, but is probably caused by a delay in the delivery of alcohol to the small intestine, from where it is rapidly absorbed.

Adult↗

Why do patients with faecal impaction have faecal incontinence.

To elucidate the phenomenon of faecal incontinence in impacted patients, manometric, radiological and other investigations were carried out in 55 elderly patients, who had impacted masses of faeces in the rectum and were incontinent of faeces and 36 elderly control subjects with no anorectal problems. Maximum basal pressure and the maximum squeeze pressure in impacted patients were not significantly different from elderly controls. Sphincter pressures were no different after disimpaction than they were with faecal masses in situ, suggesting that leakage and soiling were not caused by stretching of the anal ring or prolonged reflex inhibition of anal tone by the faecal mass. The anorectal angle was more obtuse in impacted patients than in elderly controls though there was no greater degree of perineal descent. Anal and perianal sensation was impaired in impacted patients compared with controls. Rectal sensation was also impaired in the impacted patients in that the volume in a rectal balloon that could be perceived by the subject and the volume that gave rise to a desire to defecate were much higher in impacted patients than in controls. The rectal volume required to cause anal relaxation was lower in impacted patients compared with controls though there was no reduction in the volume at which anal relaxation failed to recover its resting tone. Rectal distension elicited external sphincter contractions in 53% impacted patients compared with 80% of controls. In conclusion, faecal soiling in patients with faecal impaction is probably related to the combination of an obtuse anorectal angle and the low anal pressures, normally found in the elderly and to impaired anorectal sensation which prevents conscious contraction of the external sphincter when the internal sphincter is relaxed.

Aged↗

Simultaneous measurement of gastric emptying, small bowel residence and colonic filling of a solid meal by the use of the gamma camera.

A method for determining the profiles of gastric emptying, small intestinal residence, and colonic filling of a solid test meal, labelled with 250 microCi 99mTechnetium sulphur colloid has been evaluated in nine healthy volunteers and six patients with a disturbance in bowel habit. Mean small bowel transit time was determined by deconvolving the rate of colonic filling with the rate of gastric emptying. In normal subjects, the stomach appeared to empty exponentially with a half time of 1.2 +/- 0.3 hours (mean +/- SD). Food reached the colon by 2.8 +/- 1.5 hours. The mean small bowel transit time was 4.0 +/- 1.4 hours. In most normal subjects, the colon appeared to fill in a linear fashion with approximately 16% food residues entering every hour, and the profile of colonic filling in normal subjects was similar to the profile of ileal emptying observed after feeding a similar radiolabelled solid meal to 14 patients equipped with terminal ileostomies. There was a highly significant correlation between the onset of breath hydrogen excretion and the appearance of radioactivity over the caecum (r = 0.88, p less than 0.01), though in one third of subjects the increase in caecal radioactivity preceded the rise in breath hydrogen concentration by more than 20 minutes. There was also a highly significant correlation between the mean transit time and values for colonic filling but not values for gastric emptying. Patients with irritable bowel syndrome who had diarrhoea tended towards short small bowel transit and early colonic filling, whereas patients who have constipation tended towards long small bowel transit and delayed colonic filling. This method offers a novel means of assessing small bowel transit time, small bowel residence and the profile of colonic filling in man.

Adult↗

Effect of clindamycin on the ability of a continuous culture of colonic bacteria to ferment carbohydrate.

A continuous culture model of the proximal colon was used to study the effect of clindamycin on the ability of colonic bacteria to ferment carbohydrate. Six steady state anaerobic cultures of human faeces, in a medium simulating ileostomy effluent, were treated with 26 micrograms/ml clindamycin. They were paired with six untreated cultures, run under identical conditions. Clindamycin treatment eliminated the anaerobic bacteria, significantly decreased osmolality and the output of volatile fatty acids, particularly propionic acid and increased the residual carbohydrate concentration. Doubling the amount of carbohydrate in the medium increased osmolality and the production of volatile fatty acid, though the response of clindamycin treated cultures was less than that of untreated cultures. Attempts to introduce Clostridium difficile into three pairs of cultures were successful in only two cultures after administration with clindamycin and when a heavy inoculum (10(6)-10(9) organisms) had been used.

Bacteria↗

Effect of two new antisecretory drugs on fluid and electrolyte transport in a patient with secretory diarrhoea.

The effect of oral lidamidine hydrochloride and subcutaneous long acting somatostatin analogue, SMS 201-995, on stool output and salt and water transport in the small intestine was investigated in a patient with gross secretory diarrhoea caused by a vasoactive intestinal polypeptide (VIP) secreting tumour in the liver. Transport in the jejunum and ileum were assessed by steady state perfusion techniques. Under basal conditions, the patient was absorbing fluid and electrolytes from the jejunum and ileum, but at rates that were abnormally low. Lidamidine had no effect on either intestinal transport or stool frequency and output. SMS 201-995 increased intestinal absorption in the jejunum and ileum, reduced plasma VIP concentrations, daily stool frequency and weight, and enabled the patient to resume a normal diet without oral or intravenous fluid and electrolyte supplements. After two months of treatment, medical control was becoming increasingly difficult and stool output had risen again to 2 litres per day. Surgical resection, fortunately, was possible and led to resolution of symptoms and normal plasma VIP concentrations.

Adult↗

Neural control of jejunal and ileal motility and transmural potential difference in the ferret.

The aim of the present study was to examine the vagal control of motor activity and transmural potential difference in the anaesthetized ferret jejunum and ileum in vivo. The data suggest that in the jejunum fluctuations in transmural potential difference occur secondary to spontaneous bursts of contractions and both are controlled by activity in the vagus nerve. However, in the ileum, spontaneous contractile activity and transmural potential difference are not under the tonic influence of the vagus nerve, although transmural potential difference may be under tonic sympathetic control. Furthermore, it appears that vagally induced motor activity and transmural potential difference responses are independent phenomena. Finally the changes in transmural potential difference and the long latency motor responses to vagal nerve stimulation in the small intestine of the ferret are mediated at least in part by noncholinergic transmitters.

Adrenergic alpha-Agonists↗

Diarrhée motrice.

The gut is a long convoluted tube, in which food is processed and nutrients, salt and water are absorbed. The degree of absorption depends to a large extent on the degree of contact between the luminal contents and the absorptive epithelium. Motor activity can influence the degree of absorption because it regulates the degree of contact with the epithelium and it may also induce secretion by a reflex mechanism. Many factors that induce diarrhoea are associated with 'abnormal' and highly propagative forms of motor activity that can clear material through the gut, allowing insufficient epithelial contact for absorption. These propulsive motor patterns may be provoked by distension of the gut with fluid, but they can also occur in response to diarrhoeogenic factors when there is minimal distension. Patients who complain of increased frequency, urgency and incontinence but pass normal stool volumes often have an abnormality in the motor activity of the anorectum. Thus, the generation of abnormal or propagated forms of motor activity must be regarded as an important component of the pathogenesis of all types of diarrhoea and an increased stool volume can be regarded as the end result of a vicious spiral (Figure 12) that may start with a primary abnormality in either motor activity or epithelial transport.

Action Potentials↗

Metabolism of mixed human colonic bacteria in a continuous culture mimicking the human cecal contents.

The purpose of this study was to develop an in vitro model of the proximal colon that would permit investigation of the function of colonic bacteria. Five continuous cultures of fecal bacteria were maintained anaerobically in steady state for at least 21 days in a medium simulating ileostomy effluent. The pH was maintained at 6 by the controlled infusion of sodium bicarbonate. Fresh medium (13 ml) was pumped into the culture for 2 min every hour and excess culture was simultaneously removed. The redox potential of all cultures remained below -300 mV, whereas the osmolality was maintained hypertonic compared with the original inoculum or medium. The cultures readily produced volatile fatty acids at a rate of 30.4 +/- 3.6 mmol/day (mean +/- SEM). Acetic acid (10-19 mmol/day) and propionic acid (5-30 mmol/day) were produced in the largest amounts, whereas butyric acid was produced only in small amounts or not at all. Ammonia was produced in each culture in amounts that varied from day to day and between cultures. The osmolality and volatile fatty acid production increased when the carbohydrate input was doubled and decreased when the cultures were deprived of carbohydrate. Thus it is possible to maintain actively fermenting viable cultures in vitro for prolonged periods; such cultures respond to changing conditions and may be useful in investigating the metabolic function of the colon.

Bacteria↗

Anorectal function in elderly patients with fecal impaction.

Manometric and other investigations were carried out in 55 elderly patients who had impacted masses of feces in the rectum upon admission to hospital and in 36 elderly age- and sex-matched control subjects. Maximum basal and maximum squeeze sphincter pressures in the patients were similar to those in the elderly controls. Most elderly patients in the impacted group and all control subjects were able to pass a 50-ml balloon from the rectum, although a lower proportion of patients, admitted with impaction, could expel a small solid sphere. In patients the rectum had to be distended with larger volumes than in controls before the presence of the rectal balloon, pain, and the desire to defecate were perceived and before rectal contractions were generated. Rectal pressures, recorded during rectal distention, were lower in the impacted group than in the control group. Finally, anal and perianal sensation was impaired in patients with fecal impaction. These findings are similar to those described in patients with low spinal cord injuries.

Aged↗

Effect of ileal and intravenous infusions of fat emulsions on feeding and satiety in human volunteers.

The effect of ileal infusion of a lipid emulsion, containing 50% corn oil and 3% albumen, on food intake and satiety was measured in paired experiments carried out in 6 healthy volunteers. Subjects ate for shorter periods of time during ileal infusions of fat emulsion compared with control infusions of albumen and saline (25 +/- 1 vs. 32 +/- 3 min, mean +/- SEM) and consumed a smaller amount of food (670 +/- 23 g vs. 884 +/- 89 g) and energy (1016 +/- 79 kcal vs. 1591 +/- 228 kcal). The quantity of liquid drunk and the rates of eating and drinking were not significantly affected by the infusion of fat emulsion. In a further series of experiments carried out in 5 normal volunteers, ileal infusion of corn oil emulsions delayed gastric emptying compared with ileal infusion of albumen and saline (t1/2 = 203 +/- 48 vs. 68 +/- 12 min, p less than 0.02). The possibility that the observed reductions in food intake were related to the effect of absorbed fat was investigated in 6 healthy volunteers during intravenous infusion of either fat emulsion or isosmotic saline. Food intake was not affected by intravenous infusion of lipid. Our results suggest that lipid may interact with ileal receptors to induce early satiety and reduce the amount of food consumed. The earlier inhibition of food intake during lipid infusion is perhaps best explained by early gastric distention caused by delayed gastric emptying, though the data would not exclude the release of an ileal mechanism, which has a direct action on the satiety centers.

Adolescent↗

Effect of ileal infusion of intralipid on gastrointestinal transit, ileal flow rate, and carbohydrate absorption in humans after ingestion of a liquid meal.

The effects of ileal infusion of Intralipid on the time required for a radiolabeled liquid starch meal to empty from the stomach and reach a point in the ileum that was 230 cm from the teeth and on the ileal flow rates and the degree of carbohydrate absorption were measured in 5 normal volunteers. The subjects were intubated with a four-lumen polyvinyl tube. Studies were carried out on consecutive days in random order. Infusion of fat into the ileum (a) slowed the transit of a liquid meal through the stomach, (b) delayed the arrival of the liquid meal in the ileum and increased its residence in the upper small intestine, (c) reduced the average flow of digesta through the upper small intestine and altered the pattern of flow, (d) reduced the volume of the meal entering the ileum, and (e) reduced the degree of carbohydrate absorption in the upper small intestine. These results suggest that the presence of fat in the ileum may have a profound influence on the digestion and absorption of a meal.

Adolescent↗

The effects of pH on colonic bacteria grown in continuous culture.

A model of the proximal colon was used to investigate the effects of pH on fermentation by colonic bacteria in vitro. Twelve continuous anaerobic cultures of human faecal bacteria were maintained at constant pH in a medium simulating ileostomy effluent. Five cultures were maintained at pH 7, five at pH 6, and two at pH 5. The pH of each of three further cultures was altered after they had reached steady state, either from 7 to 6 and then to 5, or from 5 to 6 to 7. Both experimental designs showed that the pH exerted an important effect on bacterial metabolism without causing major changes in bacterial populations. Osmolality was lower in cultures run at a low pH. Total volatile fatty acid concentration was decreased at pH 5, and the production of propionic acid rather than acetic acid was favoured at pH 6. Changing the pH had no significant influence on the production of ammonia in these systems.

Ammonia↗