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Biomedical subjects

D F Evans

Publications and source records attributed to D F Evans.

At least 73 records · Page 4Linked to original sources

A double-blind dose ranging study of BRL 24924 and metoclopramide on lower oesophageal sphincter pressure in healthy volunteers.

1. A double-blind placebo controlled dose ranging study of the effect of single oral doses of 1 and 2 mg BRL 24924 and 10 mg metoclopramide on lower oesophageal sphincter pressure has been performed in 20 healthy volunteers. 2. The 2 mg dose of BRL 24924 caused a statistically significant increase in mean lower oesophageal sphincter pressure (P less than 0.05) at 30-45 min post-dose (20.8 +/- 7.1 cm H2O BRL 24924; 16.4 +/- 5.7 cm H2O placebo). BRL 24924 1 mg and metoclopramide 10 mg failed to increase lower oesophageal sphincter pressure at any time. However, eight volunteers with a hypotensive resting lower oesophageal sphincter pressure (less than 15 cm H2O) showed a statistically significant rise in pressure at 120 min for both 1 mg, 2 mg (P less than 0.01; P less than 0.001) BRL 24924 and 10 mg metoclopramide (P less than 0.01). No other significant effect was detected on oesophageal manometry. 3. BRL 24924 (2 mg) has statistically significant effects on lower oesophageal sphincter pressure. However, further studies in patients with gastro-oesophageal reflux disease and oesophagitis are needed to evaluate its clinical efficacy, especially where a hypotensive lower oesophageal sphincter pressure predominates.

Adult↗

Gastrointestinal tract: dynamic MR studies with echo-planar imaging.

Gastrointestinal (GI) tract motility was depicted in four human volunteers with the high-speed echo-planar imaging technique: modulus blipped echo-planar single-pulse technique (MBEST). Data acquisition times of 64 and 128 msec obviate image degradation due to motion without the need for gut paralysis and allow imaging of the GI tract in real time. Peristaltic patterns of the gastric antrum and proximal small intestine were depicted for fasting and fed subjects and subjects in whom peristalsis had been pharmacologically stimulated. The potential for quantitative measurements of GI tract motion with this new technique was demonstrated.

Adult↗

Gastrointestinal transit of Sinemet CR in healthy volunteers.

The gastrointestinal transit and systemic absorption of Sinemet CR (50/200) and standard Sinemet (25/100) have been studied in fasting and "fed" healthy human subjects. Both formulations were labeled with a gamma-emitting radionuclide, and their gastric emptying, colon arrival, and in vivo dissolution profiles were monitored using gamma scintigraphy. The standard dosage forms were found to disperse soon after administration and to empty rapidly from both the fasting and the "fed" stomach. The erosion of the controlled-release (CR) system was independent of food. Dosing after a light breakfast altered the gastric emptying profile of the CR formulation and led to significant differences in the plasma levels of levodopa.

Antiparkinson Agents↗

An evaluation of applied potential tomography in the diagnosis of infantile hypertrophic pyloric stenosis.

In a study of gastric emptying on 28 children using applied potential tomography, we have shown that a group of children with delayed gastric emptying can be identified, including those with proven hypertrophic pyloric stenosis. The place of APT in the investigation of gastric emptying in children is discussed, and in particular its usefulness in early confirmation of HPS in equivocal cases.

Diagnosis, Differential↗

A double-blind placebo-controlled trial of BRL 24924 on lower oesophageal sphincter pressure and gastro-oesophageal reflux in healthy volunteers.

BRL 24924 is a new gastrointestinal prokinetic agent with properties similar to metoclopramide but with increased potency and devoid of side-effects associated with blockade of dopamine receptors in the central nervous system. A double-blind placebo-controlled trial of the effect of a single oral dose of 2.2 mg BRL 24924 on lower oesophageal sphincter pressure and gastro-oesophageal reflux has been performed in 20 healthy volunteers. BRL 24924 significantly increased mean lower oesophageal sphincter pressure (21.9 cmH2O BRL; 15.9 cmH2O placebo: P less than 0.017) but failed to alter either the frequency or the duration of gastro-oesophageal reflux after provocation following a test meal. BRL 24924 has significant effects on lower oesophageal sphincter pressure but no effect on provoked post-prandial reflux in healthy volunteers. Further studies in patients with gastro-oesophageal reflux and oesophagitis are needed to evaluate the clinical efficacy of this compound.

Adult↗

Measurement of gastrointestinal pH profiles in normal ambulant human subjects.

Gastrointestinal (GI) pH has been measured in 66 normal subjects using a pH sensitive radiotelemetry capsule passing freely through the gastrointestinal tract. Signals were recorded with a portable solid state receiver and recording system, enabling unconstrained measurements with normal ambulatory activities for up to 48 h during normal GI transit. Capsule position in the gut was monitored by surface location using a directional detector. Gastric pH was highly acidic (range 1.0-2.5) in all subjects. The mean pH in the proximal small intestine was 6.6 (0.5) for the first hour of intestinal recording. By comparison the mean pH in the terminal ileum was 7.5 (0.4) (p less than 0.001). In all subjects there was a sharp fall in pH to a mean of 6.4 (0.4) (p less than 0.001) as the capsule passed into the caecum. Values are means (SD). pH then rose progressively from the right to the left colon with a final mean value of 7.0 (0.7) (p less than 0.001).

Adult↗

Ileal pH in cystic fibrosis.

In cystic fibrosis jejunal hyperacidity has an adverse effect on lipid digestion. It is not known whether hyperacidity extends to the ileum. We have studied pH through the whole length of the small bowel in 42 normal and 6 cystic fibrosis subjects by means of pH-sensitive radiotelemetry capsules. In cystic fibrosis subjects the time spent below pH 6.0 was significantly greater during the 1st h in the small bowel than in normal subjects. In the rest of the small bowel the pH remained above 6.0 in both groups. The recordings in the cystic fibrosis group did not show the clear distinction between ileum and colon which is seen in normal subjects. In cystic fibrosis low pH conditions are confined to the proximal small intestine. There is adequate time at optimal pH in the small bowel for dissolution of enzyme supplements and assimilation of nutrients.

Adult↗

The effect of insulin-induced hypoglycaemia on gastrointestinal motility in man.

The effect of insulin-induced hypoglycaemia on gastro-jejunal motility was studied in five, healthy, male subjects using tethered, pressure sensitive, radiotelemetry capsules. Thirty minutes after the intravenous injection of soluble insulin (0.15 unit/kg body weight), a significant reduction in blood glucose concentration (control: 5.26 +/- 0.19 SEM mmol/l; insulin: 1.48 +/- 0.44 mmol/l; P less than 0.001) was associated with a rise in heart rate (mean peak rise 29 +/- 8 beats/min, P less than 0.05), systolic arterial blood pressure (mean peak rise 28 +/- 4 mmHg, P less than 0.01) and plasma pancreatic polypeptide concentration (control: 20 +/- 7 pmol/l; insulin: 287 +/- 66 pmol/l; P less than 0.01). These events coincided with a short period of jejunal motor activity, which was not associated with gastric motor activity nor with raised plasma motilin concentrations. During the control study, there were no changes in blood glucose concentration, heart rate, arterial blood pressure or plasma pancreatic polypeptide concentrations, and there was no jejunal motor activity. The interval between successive gastric migrating motor complexes (MMC) was not significantly different in the insulin and control studies (control: median interval 110 min, range 108-148 min; insulin: median interval 124 min, range 115-125 min), suggesting that the fasting gastrojejunal MMC and jejunal motor activity arose independently. Insulin-induced hypoglycaemia is accompanied by jejunal motor activity, which may underlie the abdominal symptoms associated with hypoglycaemia.

Adult↗

Twenty four hour oesophageal acidity in achalasia before and after pneumatic dilatation.

Radiotelemetric ambulatory 24 hour oesophageal pH measurement was carried out in 17 patients with symptomatic manometrically proven achalasia before and after pneumatic dilatation. Before dilatation an abnormally high percentage acid exposure time was present but typical episodes of gastro-oesophageal reflux occurred in only one patient. In nine patients who had a oesophageal food residue these values were significantly greater than those found in the remaining patients without retained food. Analysis of oesophageal food residues revealed that the low pH was predominantly caused by lactic acid. These findings indicate that preoperative oesophageal pH studies do not offer a valid means of selection of patients in whom an antireflux procedure should be combined with cardiomyotomy. Repeat studies one week after pneumatic dilatation showed a fall in the acid exposure time in patients with initial food residue presumably resulting from improved oesophageal emptying after treatment. A significant rise in acid exposure time after dilatation was seen in those patients without initial food residue presumably resulting from gastro-oesophageal reflux after therapeutic disruption of the lower oesophageal sphincter. Troublesome symptoms of gastro-oesophageal reflux were, however, uncommon after bag dilatation.

Adolescent↗

Ambulatory esophageal pH monitoring in children as an indicator for surgery.

Twenty-four-hour esophageal pH monitoring was performed in 59 children with symptoms of gastroesophageal reflux using a miniature pH electrode and a portable recording system to establish the diagnosis. Significant reflux was seen in 26 (44%) of the patients and these were treated for six weeks with cimetidine, Gaviscon, and Nestargel. Five children who did not improve either symptomatically or on repeat pH monitoring while on treatment underwent antireflux surgery. The pretreatment reflux index in this group was 26.5 compared with a pretreatment reflux index of 11.2 in the 21 patients who improved on therapy (P less than 0.01). Esophageal pH monitoring has enabled selection of children for surgery and may be used as an early indicator of those who will not benefit from long-term medical therapy. Ambulatory and home monitoring techniques are more convenient and cost-effective and allow studies to be performed in the normal home environment.

Antacids↗

Attractive forces between uncharged hydrophobic surfaces: direct measurements in aqueous solution.

Long, double-chained alkylammonium acetate surfactants are soluble in water and, under suitable conditions, adsorb onto sheets of muscovite mica, forming an electrically neutral, hydrophobic surface. Attractive forces measured between such surfaces are 10 to 100 times stronger than expected from van der Waals theory over distances D up to about 10 nanometers. The forces decay exponentially [with a force proportional to exp(-D/1.4)] instead of following the power-law behavior of continuum theory. The results of these and earlier experiments indicate that the strength of these attractive forces depends critically on the degree of hydrophobicity of the surface and is due to the long-range influence of the surface on the structure of water. In addition, for very hydrophobic surfaces, the cavitation effects on pulling the surfaces apart are described.

Adsorption↗

The influence of tumour cell DNA abnormalities on survival in colorectal cancer.

The cellular DNA content was measured from paraffin-embedded material in 134 colorectal cancers from patients in whom the outcome was known. Seventy-two (55 per cent) were found to contain cells with abnormal DNA (DNA aneuploid). The presence of such a population of cells was not related to pathological stage or histological grade. However, only 14 (19 per cent) patients with DNA aneuploid tumours survived 5 years compared with 27 (43 per cent) of patients with diploid tumours (chi 2 = 8.0, P = 0.005). Stepwise logistic analysis showed cellular DNA content to be an important prognostic factor in colorectal cancer, independent of pathological stage and histological grade.

Aneuploidy↗

Reflux versus dysphagia: an objective evaluation of the Angelchik prosthesis.

Twenty-seven patients with proven longstanding gastro-oesophageal reflux underwent insertion of an Angelchik anti-reflux prosthesis. Preoperative studies included oesophageal manometry, endoscopy, acid reflux provocation test (ARPT) and 24 h oesophageal pH recording (24 h pH). Following operation mean lower oesophageal sphincter pressure was increased from 11 to 20 cmH2O. ARPT revealed significant pre-prandial reflux before operation in 16/24 compared with only 1/20 postoperatively; 24 h pH also showed an improvement in that 21/22 patients refluxed before operation compared with no significant reflux after. Dysphagia for solids of some degree was seen postoperatively in 26 patients and this was also demonstrated by delay in transit of a marsh-mallow swallow test. Severe dysphagia was seen in 4 patients and in 3 of these was related to rotation and displacement of the prosthesis necessitating removal.

Deglutition Disorders↗

A frequency-duration index (FDI) for the evaluation of ambulatory recordings of gastro-oesophageal reflux.

Oesophageal pH monitoring has been undertaken in 20 symptomatic patients and 20 normal subjects for periods of 24 hours at work and in the home using a pH sensitive radiotelemetry capsule and a portable receiving system. There was no correlation between symptoms and endoscopic findings in symptomatic patients. The number and duration of reflux episodes was greater in symptomatic patients than normal subjects during 24 hour ambulatory study (P less than 0.002). A frequency-duration index for the evaluation of recordings is described which was significantly greater in symptomatic patients than in normal subjects during both day (P less than 0.002) and night (P less than 0.008) periods of recording. Discrimination between the two groups was more clearly seen using the frequency-duration index compared to either the frequency of reflux episodes or the cumulative duration of acid reflux.

Adult↗

The action of porcine glucagon on the motility of the canine duodenum and jejunum.

1 Intravenous bolus doses of porcine glucagon of 0.001-0.05 mg kg-1 caused intense stimulation of the duodenum and jejunum of the dog. 2 Intravenous infusion of porcine glucagon at 0.025-0.05 mg kg-1 h-1 caused similar stimulation. In both cases the stimulation was phasic in nature. 3 Stimulation of the duodenum and jejunum following glucagon was accompanied by a decrease in frequency of the intestinal basic electrical rhythm (BER). No change was seen in the intervals between successive periods of phase III motor activity.

Animals↗

Ambulatory monitoring of oesophageal pH in reflux oesophagitis using a portable radiotelemetry system.

Gastro-oesophageal reflux has been assessed in 10 symptomatic patients and 10 asymptomatic normal subjects during a study period of 24 hours at work and in the home using a newly developed pH sensitive radiotelemetry capsule and a portable receiving system. Oesophageal pH was continuously monitored by the tethered radiotelemetry capsule and recorded with a portable receiver and a 24-hour cassette recorder, allowing the patient complete freedom of movement so that ambulatory studies could be undertaken during a normal working day. The number and duration of reflux episodes was greater in symptomatic patients than normal subjects during 24-hour studies at home (p less than 0.002). In both groups, reflux occurred more during the day than at night (p less than 0.01). Patients refluxed significantly more at home than when they were in hospital (p less than 0.01). Ambulatory outpatient oesophageal pH monitoring may be useful in the management of patients with atypical symptoms and may demonstrate significant reflux when inpatient investigations and endoscopy findings show minimal abnormality.

Adult↗