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Biomedical subjects

N W Read

Publications and source records attributed to N W Read.

At least 55 records · Page 3Linked to original sources

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

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

Adult↗

Effects of a specific CCK-A antagonist, Loxiglumide, on postprandial mood and sleepiness.

Previous studies have demonstrated that feelings of sleepiness increase after ingestion of a fat-rich meal. The aim of the study was to test the hypothesis that postprandial sleepiness is mediated by cholecystokinin (CCK) acting on CCK-A receptors. A double-blind crossover study was conducted. Twelve male volunteers ate a high-fat morning meal [54% energy fat, 41% energy carbohydrate (CHO)]. On one day they received an i.v. infusion of Loxiglumide, a CCK-A receptor antagonist (30 mg/kg/h for 10 min then 10 mg/kg/h for 3 h 10 min). On another day the protocol was repeated except a saline placebo infusion was given at similar rates as the Loxiglumide, starting 20 min before the meal. Subjects' mood and sleepiness were monitored throughout using questionnaires and performance tasks. The results indicate that ratings of vigour were significantly lower during the Loxiglumide infusion than during the saline infusion, [F(1,10) = 6.65; p = 0.027]. Subjects who were infused with Loxiglumide on their first test day felt significantly (p < 0.05) more fatigued, sleepy and tense and less vigorous, less efficient and had lower energetic arousal during the Loxiglumide infusion than during the saline infusion. In conclusion, the results suggest that the postprandial decline in feelings of alertness after a fat-rich meal is not mediated solely by CCK acting through CCK-A receptors.

Adult↗

Effects of loperamide oxide on gastrointestinal transit time and anorectal function in patients with chronic diarrhoea and faecal incontinence.

BACKGROUND: Loperamide improves anorectal function in patients with chronic diarrhoea. We wished to investigate whether the prodrug loperamide oxide has similar effects. METHODS: Eleven patients with chronic diarrhoea and faecal incontinence participated in a randomized, placebo-controlled, double-blind, crossover study of the effects of loperamide oxide (4 mg twice daily for 1 week). RESULTS: Loperamide oxide reduced wet stool weight and improved the patients' ratings of symptoms. Mouth-to-caecum transit time was not altered, but whole-gut transit time was prolonged. There were limited effects on anorectal function, but the mean minimum basal pressure mainly contributed by the internal anal sphincter (IAS) was increased, as was the mean volume infused before leakage occurred in the saline continence test. CONCLUSION: Loperamide oxide is effective in the treatment of diarrhoea with faecal incontinence; normalization of colon transit time and an increase in the tone of the IAS seem to be the main determinants of efficacy.

Adult↗

Psychometric scores and persistence of irritable bowel after infectious diarrhoea.

BACKGROUND: Although previous studies have shown that psychological disturbances are frequently associated with the irritable bowel syndrome (IBS), the relation was not necessarily cause and effect. The development of chronic bowel symptoms resembling IBS after an episode of acute gastroenteritis has allowed us to examine prospectively the role of psychological factors. METHODS: 75 patients with acute gastroenteritis completed a series of psychometric tests soon after admission to hospital. Of these, 22 had persistent symptoms compatible with IBS after the acute illness, and in 20 of these the symptoms were still present at six months. FINDINGS: At the time of their initial illness, patients who subsequently developed IBS symptoms had higher scores for anxiety, depression, somatisation, and neurotic trait than those who returned to normal bowel function. The psychometric scores had not changed when remeasured three months after the acute illness. Lactose malabsorption was not an important factor. INTERPRETATION: These results support the hypothesis that psychological factors are important in IBS.

Acute Disease↗

The effect of short-term dietary supplementation with glucose on gastric emptying of glucose and fructose and oral glucose tolerance in normal subjects.

Recent observations indicate that gastric emptying may be influenced by patterns of previous nutrient intake. The aims of this study were to determine the effects of a high glucose diet on gastric emptying of glucose and fructose, and the impact of any changes in gastric emptying on plasma concentrations of glucose, insulin and gastric inhibitory polypeptide in response to glucose and fructose loads. Gastric emptying of glucose and fructose (both 75 g dissolved in 350 ml water) were measured in seven normal volunteers on separate days while each was on a "standard' diet and an identical diet supplemented with 440 g/day of glucose for 4-7 days. Venous blood samples for measurement of plasma glucose, insulin and gastric inhibitory polypeptide levels were taken immediately before and for 180 min after ingestion of glucose and fructose loads. Dietary glucose supplementation accelerated gastric emptying of glucose (50% emptying time 82 +/- 8 vs 106 +/- 10 min, p = 0.004) and fructose (73 +/- 9 vs 106 +/- 9 min, p = 0.001). After ingestion of glucose, plasma concentrations of insulin (p < 0.05) and gastric inhibitory polypeptide (p < 0.05) were higher during the glucose-supplemented diet. In contrast, plasma glucose concentrations at 60 min and 75 min were lower (p < 0.05) on the glucose-supplemented diet. We conclude that short-term supplementation of the diet with glucose accelerates gastric emptying of glucose and fructose, presumably as a result of reduced feedback inhibition of gastric emptying from small intestinal luminal receptors. More rapid gastric emptying of glucose has a significant impact on glucose tolerance.

Adult↗

Influences of fat, energy, and time of day on mood and performance.

Paired studies testing the effects of lower energy high-fat, low-CHO meals (3181 kJ, fat:CHO energy ratio 54:41) and higher energy low-fat, high-CHO meals (3599 kJ, fat:CHO energy ratio 7:88) were conducted in 18 healthy males. The meals were eaten at 1030 h by group A (nine subjects) and 1230 h by group B (nine subjects). Subjective lassitude increased following ingestion of all four meals, but there was little change in performance. In addition, group A, but not group B, felt significantly less vigorous, imaginative, and antagonistic, and significantly more dreamy, feeble, and fatigued after the lower energy high-fat, low-CHO meal than after the higher energy low-fat, high-CHO meal. These results suggest that in the morning, fat exerts a greater depression on alertness and mood than carbohydrate irrespective of a reduction in energy content, but this effect varies according to the time at which food is eaten, and is less evident at lunch time.

Adult↗

Cholecystokinin-A receptors modulate gastric sensory and motor responses to gastric distension and duodenal lipid.

BACKGROUND & AIMS: The combination of duodenal lipid and gastric distention induces meal-like fullness followed by nausea in healthy subjects. The aim of this study was to assess the role of cholecystokinin (CCK) A receptors in these changes using a CCK-A antagonist loxiglumide. METHODS: Twelve healthy subjects were studied on four occasions, during which either 0.9% saline or 20% Intralipid was infused intraduodenally on two occasions each (1 mL/min) while the proximal stomach was distended with air (100 mL/min). During each duodenal infusion, subjects received intravenous loxiglumide (10 mg.kg-1.h-1) on 1 day and placebo on the other. Intragastric pressure changes were recorded, and the subjects reported gastric sensations (fullness, nausea). RESULTS: Loxiglumide did not influence gastric motility or sensitivity during duodenal saline infusion. Duodenal lipid reduced gastric tonic and phasic pressure activity during distensions and induced meal-like fullness and nausea; sensations were reported at similar volumes but lower intragastric pressures (P < 0.001 vs. saline). Loxiglumide partially restored gastric tonic and phasic activity during lipid infusion, reduced the occurrence of meal-like fullness and nausea, and increased the pressures at which sensations were reported (P < 0.001 vs. placebo). CONCLUSIONS: CCK-A receptors are involved in the induction of meal-like fullness and nausea associated with intraduodenal lipid and gastric distention.

Adult↗

Disturbances in anorectal function in patients with diabetes mellitus and faecal incontinence.

OBJECTIVE: The pathophysiology of faecal incontinence in diabetes mellitus is poorly understood. The study was designed to document the anorectal dysfunctions in diabetic patients with faecal incontinence. METHODS: Multiport anorectal manometry and electromyography were done in 11 diabetic patients with faecal incontinence and in 20 healthy controls. RESULTS: Basal and squeeze pressures were reduced (P < 0.05) in the diabetic patients compared with the control subjects. During basal recording six patients showed regular oscillations in anal electrical activity and pressure with an amplitude of 10-40 (median: 25) cmH2O and a frequency of 6-10 (median: 8) min-1. Nine patients also exhibited spontaneous transient anal relaxations with an amplitude of 15-50 (median: 40) cmH2O and a duration of 15-720 (median: 60)s, and in six of them leakage occurred as the anal pressure fell below the rectal pressure. None of the control subjects showed oscillation or spontaneous relaxations. In patients there was a greater tendency for repetitive rectal contractions in response to rectal distension and reduced rectal compliance (P < 0.01). During rectal distension four patients showed no anal relaxation, and in the remainder relaxation occurred at an abnormally high threshold. However, the residual pressures were lower (P < 0.05) than in control subjects and often fell below rectal pressure, whereupon leakage occurred. There was no significant difference in the distension thresholds for rectal sensation between patients and control subjects, but in 9/11 patients the perception of rectal sensation was delayed by more than 2s (P < 0.05). CONCLUSION: These results indicate that aetiology of faecal incontinence in diabetic patients is multifactorial and, suggest for the first time, that instability of the internal sphincter probably plays a major role.

Adult↗

Appetite regulation by carbohydrate: role of blood glucose and gastrointestinal hormones.

To investigate the mechanisms by which intestinal carbohydrate affects eating behavior, seven fasted, healthy male volunteers received intraduodenal infusions of glucose or saline over a 90-min period while blood glucose levels were matched by use of intravenous glucose and saline infusions. A second study examined the effect of intraduodenal glucose on eating behavior when the gastrointestinal hormone response was inhibited by intravenous octreotide. Intravenous glucose infusion did not affect hunger or satiety. In contrast, intraduodenal infusion of glucose suppressed hunger, increased fullness and satiety ratings, reduced energy intake, and resulted in higher plasma insulin responses compared with the intravenous glucose infusion. Octreotide abolished the plasma insulin response to intraduodenal glucose and reversed the changes in ratings and eating behavior. This study has shown that the effects of intestinal glucose on appetite are not mediated via an increase in blood glucose but are likely to reflect small intestinal stimulation of release of either insulin or intestinal incretins.

Adult↗

Role of cholecystokinin as a regulator of solid and liquid gastric emptying in humans.

The role of endogenous cholecystokinin (CCK) in the regulation of gastric emptying remains controversial. We therefore studied the effect of the CCK-A receptor antagonist loxiglumide on gastric emptying of a high-caloric solid-liquid meal in humans. Gastric emptying was assessed in eight volunteers using intravenous loxiglumide or placebo in a randomized double-blind order. Subjects were studied by a dual-headed gamma camera after ingestion of a pancake (570 kcal) labeled with 99mTc-sulfur colloid and 500 ml 10% glucose containing 111In-diethylenetriamine pentaacetic acid. Plasma CCK was measured by a specific radioimmunoassay. Loxiglumide markedly accelerated gastric emptying of both phases of the meal. The lag period was shortened by 26% (P < 0.03); the area under the emptying curve and half-emptying time of solid emptying were lowered by 19 and 24% (P < 0.02) and of liquid emptying by 18 and 24% (P < 0.04), respectively. Plasma CCK levels were higher during infusion of loxiglumide compared with placebo (P < 0.02). These data demonstrate that post-prandially released CCK is a major regulator of gastric emptying of physiological meals containing both solid and liquid components.

Adult↗

Ondansetron reduces nausea induced by gastroduodenal stimulation without changing gastric motility.

The involvement of 5-hydroxytryptamine3 (5-HT3) receptors in gastric motor and sensory responses to distension and duodenal lipid was investigated. Subjects were studied on four occasions during which isotonic saline or 20% Intralipid (2 kcal/ml) was infused intraduodenally (1 ml/min) while the proximal stomach was distended with air (100 ml/min). Subjects received either 8 mg ondansetron (5-HT3 antagonist) or placebo orally in random order. Intragastric pressure was recorded continuously, and subjects reported gastric sensations. Gastric motor and sensory responses to distension during duodenal saline were similar with placebo and ondansetron. Intraduodenal lipid decreased gastric tonic and phasic pressure activity, and this was not influenced by ondansetron. Lipid also induced meal-like fullness followed by nausea during distensions. Ondansetron reduced nausea and did not affect meal-like fullness but increased volumes and pressures at which sensations were reported. Intestinal 5-HT3 receptors are involved in induction of nausea but not of meal-like fullness by intraduodenal lipid and gastric distension. 5-HT3 receptor antagonism reduces gastric sensitivity to distension during intraduodenal lipid infusion.

Adult↗

The effect on hunger and satiety of slowing the absorption of glucose: relationship with gastric emptying and postprandial blood glucose and insulin responses.

To investigate the relative potency of short-term control mechanisms for carbohydrate satiety, ten fasted, healthy male volunteers consumed a 250-ml, 30% glucose drink with and without the addition of guar gum (2%). Gastric emptying, hunger and fullness ratings and blood glucose and insulin levels were monitored over the following 3 h and energy intake was recorded from a test meal given 3.5 h after the drinks. The addition of the guar gum to the glucose drink lowered both postprandial glucose and insulin levels over the following 2 h. This was associated with a reduction in the ratings for hunger and desire to eat and an increase in ratings for fullness and satiety, but energy intake from the test meal was unchanged. There was no difference between values for the half time for gastric emptying for the two drinks. The short-term increase in satiety and decrease in hunger seen when glucose absorption was slowed with guar gum is unlikely to be explained by the reduction in postprandial glycaemia or differences in gastric emptying, and instead may implicate increased contact of the carbohydrate with receptors in the small intestine and consequent enhanced release of putative satiety peptides.

Adult↗

Functional bowel disorders. A multicenter comparison of health status and development of illness severity index.

In a multicenter study of patients with painful functional bowel disorders (FBD), we compared the demographic, health status, and diagnostic features of patients with FBD and developed a functional bowel disorder severity index (FBDSI) for research and clinical care. Two hundred seventy patients with FBD in the United States, England, and Canada were surveyed on symptoms and health status, and their physicians made a diagnosis and rated illness severity as mild, moderate, or severe. Comparisons of 22 demographic and clinical variables were made by study site in addition to physicians' severity ratings. To develop the FBDSI, multiple regression analysis used the demographic and clinical variables to predict the physician's rating of severity. We found that most health status measures of patients with FBD across study sites are comparable and the derived and validated FBDSI scoring system uses three easy to obtain variables: FBDSI = [current pain by visual analog scale (0-100)] + [diagnosis of chronic functional abdominal pain (0 if absent and 106 if present)] + [number of physicians visits over previous six months x 11]. The FBDSI can be used to select patients for research protocols and/or follow their clinical outcome or response to treatments over time.

Abdominal Pain↗

Nutrient-specific modulation of gastric mechanosensitivity in patients with functional dyspepsia.

Intraduodenal lipid infusion induces symptoms and increases sensitivity to gastric distension in patients with functional dyspepsia. To test whether these effects are specific for lipid, we compared the effects of intraduodenal infusions of either lipid or glucose on symptoms and gastric sensory and motor responses to gastric distension. Eighteen dyspeptic patients and nine controls were studied. The stomach was distended with a flaccid bag during isocaloric infusions (1 kcal/ml) of saline and either 10% Intralipid (nine patients) or 26.7% glucose (nine patients) into the duodenum. Dyspeptic symptoms and sensory thresholds for epigastric fullness and discomfort were assessed. Gastric pressure profiles during distensions were similar during lipid and glucose infusions in patients and controls, but both were significantly lower than during saline infusion. Lower volumes were required to induce fullness and discomfort in the patients compared with the controls. In the controls, the threshold volumes required to induce fullness and discomfort were greater during infusion of lipid and glucose than during saline infusion, but in the patients, the threshold volumes were increased during glucose infusion but further reduced during lipid infusion. Moreover, in the patients, nausea was more common during lipid than glucose infusion and did not occur during saline. The controls did not experience any symptoms during any infusion. In conclusion, intraduodenal lipid but not glucose sensitizes the stomach to distension in patients with functional dyspepsia but not in controls.

Adult↗

Anorectal function in patients with complete spinal transection before and after sacral posterior rhizotomy.

BACKGROUND/AIMS: The implantation of spinal stimulators to facilitate defecation in patients with complete spinal transection involves division of the posterior sacral nerve roots. The aim of this study was to investigate the role of spinal reflexes in anorectal function. METHODS: Anorectal manometry and electromyography were performed in 14 patients with supraconal spinal cord transection (C6-T12) before and after complete sacral posterior rhizotomy and in 30 normal controls. RESULTS: Patients with spinal transection lost conscious control of the external anal sphincter. Reflex responses to intra-abdominal pressure and to rectal distention were eliminated after rhizotomy, indicating that they are spinal reflexes. Rhizotomy also eliminated giant rectal contractions induced by rectal distention in these patients. In contrast, the exaggerated sphincter relaxation induced by rectal distention was not influenced by rhizotomy. Discriminant rectal sensation was lost, but patients with thoracic cord lesions perceived a dull pelvic sensation during rectal distention even after rhizotomy. CONCLUSIONS: The exaggerated anorectal smooth muscle responses and absent conscious control of the anorectum may explain why patients with complete spinal transection experience uncontrollable reflex defecation, and the persistence of external anal sphincter contraction during straining may impair fecal expulsion. The elimination of these responses after posterior rhizotomy prevented reflex defecation while facilitating manual evacuation.

Adult↗

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

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

Adult↗

Adaptation to high-fat diets: effects on eating behaviour and plasma cholecystokinin.

Twelve male subjects took part in a study to investigate the effects of overfeeding a high-fat diet (19.17 MJ/d; 58% energy from fat) for 2 weeks on plasma cholecystokinin (CCK) levels, food intake, and subjective feelings of hunger and fullness. Before and after the diet, subjects completed a 2-week weighed dietary inventory, formal measurements of food intake from a pre-selected appetizing evening meal were carried out, and blood samples were taken after a standard breakfast for measurement of CCK. Hunger and fullness were rated on visual analogue scales before and after each of these meals and at evening meals during the diet period. Following the high-fat diet there was a small non-significant increase in food intake from the pre-selected meal (6919 (SE 615) kJ v. 6405 (SE 540) kJ; P = 0.1) and a significant increase in the average daily food consumption measured from the diaries (10.25 (SE 0.49) MJ/d v. 9.59 (SE 0.62) MJ/d; P = 0.05). Corresponding trends of increasing feelings of hunger and declining fullness also occurred over the study period. Plasma CCK responses to the standard breakfast were raised following the diet (1285 (SE 153) v. 897 (SE 78) pM min; 3 h integrated CCK production post v. pre diet; P < 0.01) with the major differences observed at 90 and 120 min following the meal. These results suggest that the increase in food intake may be related to a down-regulation in putative CCK receptors responsible for food intake. Elevated CCK levels might suggest a corresponding down-regulation in CCK receptors responsible for feedback inhibition of CCK release.

Adaptation, Physiological↗

Influences of dietary and intraduodenal lipid on alertness, mood, and sustained concentration.

The effects of intraduodenal and dietary lipid on alertness, mood and performance in a task requiring sustained attention were investigated in two studies. The first experiment compared the effect of duodenal infusion of either 100 g/l Intralipid (8.36 kJ/min) or isotonic saline (9 g NaCl/l) in paired studies carried out on two non-consecutive days on five male volunteers. Two consecutive 3 h infusions, one of lipid, the other saline, were given blind on each day using a crossover design. Analysis of variance indicated that lipid significantly reduced alertness (P < 0.05) and affected the speed and accuracy of performance in a sustained attention task (P < 0.05). A second experiment compared the effects on eight male volunteers of two isoenergetic lunches of similar appearance, taste and protein content but differing fat and carbohydrate (CHO) contents (fat energy:CHO, 64:18 v. 7:76). Alertness was lower (P < 0.05) and responses to stimuli in a sustained attention task were slower after the high-fat meal than after the low-fat meal (P < 0.05). In conclusion, infusion of lipid into the small intestine, and the substitution of fat for carbohydrate while keeping energy and protein constant in a lunch, both cause an enhanced postprandial decline in alertness and concentration. This may be related to the presence of lipid in the small intestine.

Adult↗