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Biomedical subjects

N W Read

Publications and source records attributed to N W Read.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

Effect of hysterectomy on anorectal and urethrovesical physiology.

To investigate whether vaginal or total abdominal hysterectomy is associated with changes in anorectal and urethrovesical physiology, 26 women were studied before operation and six weeks and six months afterwards. The results showed a postoperative increase in both rectal and vesical sensitivity (p less than 0.01). Similar results were observed irrespective of the type of hysterectomy. No significant changes in rectal or bladder compliance were noted, and anal pressure and urethral pressure and length were unchanged after surgery. Whole gut transit was not affected by hysterectomy. Urinary symptoms occurred de novo in 6/26 women and gastrointestinal symptoms in 2/26 women. These results show that significant changes in rectal and vesical sensitivity occur after hysterectomy for benign disease. These persist for at least six months postoperatively but are not always associated with development of urinary or gastrointestinal symptoms.

Adult

Utility of a combined test of anorectal manometry, electromyography, and sensation in determining the mechanism of 'idiopathic' faecal incontinence.

Combined tests of anorectal manometry, sphincter electromyography and rectal sensation were carried out in 302 patients with faecal incontinence (235 women, 67 men). The results obtained were compared with 65 normal subjects (35 women, 30 men). A mechanism for incontinence was identified in all and the majority of patients had more than one abnormality. Two hundred and seventy eight patients (92%) had a weak external anal sphincter, 185 of these (67%, mostly women) also showed abnormal perineal descent, and 14 women showed clinical evidence of sphincter damage as a result of obstetric trauma. Ten per cent of patients with impaired external anal sphincter contraction showed associated evidence of spinal disease (impaired rectal sensation plus attenuated or enhanced reflex external anal sphincter activity). Unlike the other groups, the 'spinal' group contained equal numbers of men and women. Ninety seven patients (32%) had evidence of a weak internal anal sphincter. The external sphincter was also very weak and 92% of these patients also had perineal descent. Eighty two patients (27%) showed an unstable internal sphincter, characterised by prolonged 'spontaneous' anal relaxation under resting conditions and an abnormal reduction in anal pressure after conscious contraction of the sphincter or an increase in intraabdominal pressure. One hundred and forty two patients (47%) had a hypersensitive rectum associated with enhanced anorectal responses to rectal distension. All these patients had an abnormally weak external sphincter, suggesting that the hypersensitive or 'irritable' rectum should not be regarded as a cause of faecal incontinence unless accompanied by external sphincter weakness. Twenty four patients (8%) showed a normal basal and squeeze pressures and impaired rectal sensation; six showed giant rectal contractions during rectal distension. The results show that idiopathic faecal incontinence is not caused by a single abnormality, and it is suggested that combined anorectal manometry, electromyography, and sensory testing is a useful technique to identify the causes of faecal incontinence and provide a basis for appropriate treatment.

Adolescent

Relation between hysterectomy and the irritable bowel: a prospective study.

Some women with irritable bowel syndrome date the onset of symptoms to previous hysterectomy. To assess prospectively the incidence of gastrointestinal symptomatology arising de novo after hysterectomy, and to study the effect of surgery on pre-existing symptoms, 205 women completed a symptom questionnaire before and six weeks and six months after surgery. Beforehand, symptoms suggestive of irritable bowel syndrome occurred in 22% of patients. At six months after operation, 60% of these had improved or were symptom free while 20% had increased symptomatology. New gastrointestinal symptoms were present more than once per week in 10% of previously asymptomatic women. Constipation predominant irritable bowel syndrome was the commonest symptom complex seen de novo, occurring more than once per week in 5% of the group. No relation was found between new symptomatology and the type of hysterectomy, oophorectomy, or the administration of perioperative antibiotics. This study suggests that many women with pre-existing gastrointestinal symptomatology improve after hysterectomy. However, symptoms suggestive of irritable bowel syndrome do arise de novo in 10%. As hysterectomy is common, gastroenterologists can expect to see women presenting with post-hysterectomy problems.

Adult

Effect of short-chain fatty acids on contractile activity and fluid flow in rat colon in vitro.

The effect of short-chain fatty acids (SCFAs) on the contractile activity and fluid output of the large bowel of the rat was studied using an isolated segment of cecum and colon, mounted in vitro. The rate of contractile activity per minute in the proximal, mid, and distal regions of the colon was depressed by luminal infusion of associated SCFAs either as a mixture (acetic, propionic, and butyric) or individually (100 mM/pH = 4.1, in each case). Dose responses were observed for the individual fatty acids, with the 100 mM solutions eliciting a more prominent reduction in colonic motor activity than that induced by 10 mM. Neither the Na salt of the fatty acids nor an acidified Krebs solution (pH = 4.1) inhibited contractile activity or fluid output. No reduction in the rate of contractile activity was observed in the cecum with any test solutions, except 100 mM butyric acid. The data suggest that SCFAs inhibit smooth muscle contractility and resultant fluid transit.

Animals

Further evaluation of the afferent nervous pathways from the rectum.

To evaluate the visceral afferents from the rectum, we recorded cerebral evoked potentials (EPs) in 26 healthy subjects after electrical stimulation of the rectum, pudendal nerve, and posterior tibialis nerve. We found two distinctly different EPs after rectal stimulation, with differences in latencies and pattern. In 13 subjects (group 1), the EP after rectal stimulation had multiple prominent peaks with early onset latencies ranging from 22 to 29 ms (mean 26 ms). In 13 subjects (group 2), the EP after rectal stimulation had a trifid configuration due to a very prominent negative peak between 97 and 108 ms (mean 101 ms) and longer onset latencies ranging from 50 to 61 ms (mean 55 ms). Latencies after pudendal nerve and posterior tibialis nerve stimulation were similar in the two groups. On further study, we found that both types of afferent pathways are present in the distal colon, since both types of EPs were found in the same subjects either in the rectum or in the rectum and sigmoid. We speculate that the early onset EP is a visceral pathway using the same afferents as the pudendal nerve because the early onset EP after rectal stimulation appears similar in number of peaks and interpeak latencies to EPs recorded after pudendal nerve stimulation, and the late onset EP is a visceral pathway using afferents along the pelvic nerve. Early onset EPs were also recorded after sigmoid stimulation, suggesting that both kinds of EPs are visceral afferents.

Adult

Applied potential tomography. Noninvasive method for measuring gastric emptying of a solid test meal.

Applied potential tomography (APT) is a new noninvasive, nonradioactive method of measuring gastric emptying, which generates profiles of emptying of liquids that are similar to those obtained simultaneously by scintigraphy and dye dilution. This study validates the ability of APT to measure emptying of a solid beefburger test meal from the stomach by comparing the results obtained with those obtained simultaneously by scintigraphy. When acid secretion was inhibited, there was a significant correlation between the two methods for the time taken for half the meal to empty from the stomach and the amount of meal emptied at different time intervals. Furthermore, the profiles of gastric emptying obtained by APT resembled those obtained by scintigraphy in most studies. If acid secretion was not inhibited, there was no correlation between values obtained by the two methods.

Adult

Is rectosigmoid response to food modulated by proximal colon stimulation?

Rectosigmoid motor activity and postprandial breath hydrogen levels were monitored in eight healthy males under basal conditions and for 3 1/2 hr after a meal (beefburger and breadroll and ice cream incorporating 20 g lactulose). Within minutes of ingestion there was a significant increase in motility index (P less than 0.05) and also an initial temporary rise in breath hydrogen. A late increase in motor activity occurred in seven of eight subjects 123 +/- 19 min after the meal and was temporally related to the beginning of a second, much larger rise in breath hydrogen (r = 0.99; P less than 0.01). The close association between the timing of the rises in breath hydrogen and rectosigmoid motor activity would support the possibility that the latter may be generated by chemical or mechanical stimulation of the proximal colon.

Adult

Disturbed gastroduodenal motility in patients with active and healed duodenal ulceration.

Disordered gastroduodenal motility may promote duodenal ulceration by allowing prolonged acid contact with the duodenal mucosa. Using a multilumen perfused catheter incorporating 3 pH microelectrodes, antral and duodenal pH and antropyloroduodenal pressure activity were recorded in 36 subjects (10 with healed duodenal ulceration, 11 with active duodenal ulceration, and 15 healthy volunteers) during fasting and after a radiolabeled solid test meal. Correct pH probe/catheter position was continuously verified by recording transmucosal potential difference across the pylorus. Patients with active and healed duodenal ulcer had similarly disordered gastroduodenal motility. The chief abnormalities consisted of an increase in postprandial duodenal retroperistalsis (healed duodenal ulceration, 12 +/- 1 events per hour; active duodenal ulceration, 12 +/- 1; control, 6 +/- 1; mean +/- SEM: healed and active duodenal ulceration vs. control, P = 0.004 and P = 0.03, respectively), a reduction in pressure waves sweeping aborally through the duodenum after the meal (healed duodenal ulceration, 22 +/- 4 events per hour; active duodenal ulceration, 23 +/- 3; control, 34 +/- 4: healed and active duodenal ulceration vs. control, P = 0.04 and P less than 0.05, respectively), and an increased incidence of atypical, complex forms of coordinated duodenal motor activity throughout the study (postprandial data; healed duodenal ulceration, 8 +/- 1 events per hour; active duodenal ulceration, 10 +/- 1; control, 4 +/- 1: healed and active duodenal ulceration vs. control, P = 0.02 and P less than 0.02, respectively). In addition, gastric emptying of the solid test meal was significantly delayed in healed, but not active, duodenal ulceration [half-emptying time, healed duodenal ulceration 185 minutes (117-235); active duodenal ulceration 102 minutes (80-200); control 107 minutes (78-130): healed duodenal ulceration vs. control, P less than 0.009]. Duodenal bulb pH was similar in controls and patients with active duodenal ulceration; however, bulb pH was less than 4 for a significantly greater period of time in healed duodenal ulceration compared with active ulcer patients, particularly after the meal. In conclusion, duodenal ulcer disease is associated with disturbed gastroduodenal motility, even when the ulcer is quiescent and when intraduodenal acidity is low. In healed duodenal ulceration, disturbed motility may promote ulcer relapse by impairing acid clearance from the bulb. However, in active ulceration other factors such as mucosal bicarbonate secretion may have a more influential role in determining intraduodenal pH.

Adult