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Biomedical subjects

N W Read

Publications and source records attributed to N W Read.

At least 271 records · Page 15Linked to original sources
PubMed1982

Is the transit time of a meal through the small intestine related to the rate at which it leaves the stomach?

Using non-invasive techniques, we investigated how varying the size or composition of a meal altered the rate at which it passed through the stomach and small intestine in normal volunteers. Increasing the size of the meal by doubling the absorbable components delayed gastric emptying, did not significantly influence the time taken for the head of the meal to reach the caecum, but retarded the entry of the bulk of the meal residues into the caecum. Incorporating fat in the meal slowed gastric emptying, but did not significantly affect small bowel transit time. The addition of the unabsorbable disaccharide lactulose (in place of an equivalent amount of sucrose) accelerated small bowel transit time, but did not significantly influence gastric emptying. Thus, our results indicated that changes in small bowel transit time could occur independently of changes in gastric emptying in normal healthy subjects.

Adult↗
PubMed1982

Effect of prolonged exercise on the passage of a solid meal through the stomach and small intestine.

The effect of intermittent moderate exercise on the passage of a solid meal, labelled with radioactive Technetium sulphur colloid, through the stomach and small intestine was investigated by paired studies on seven healthy volunteers. Measurements of gastric radioactivity and breath hydrogen exertion were recorded every 10 minutes while subjects exercised in a controlled manner while seated on a bicycle ergometer. These were compared with values obtained during a separate experiment while the same subjects sat upright in a chair. Exercise significantly accelerated gastric emptying (control t 1/2 = 1.5 +/- 0.1 h; exercise t 1/2 = 1.2 +/- 0.1 h; p less than 0.02) but had no significant effect on small bowel transit time.

Adult↗
PubMed1982

Role of anorectal sensation in preserving continence.

The role of anal sensation in preserving continence was studied in nine healthy volunteers. Objective assessment of sphincter function by manometry and rectal saline infusion was carried out during topical anaesthesia of the anal canal using 5% lignocaine gel and during lubrication with the same amount of inert gel. Anaesthesia successfully abolished anal sensation and reduced both the amplitude and duration of the voluntary squeeze. Basal pressure was unaffected, but the rectal volume required to produce a sustained internal sphincter relaxation was increased. Saline continence was not impaired. Indeed, two subjects, who were previously unable to retain the full 1500 ml of rectally infused saline, did so when the anal canal was anaesthetised. Our findings suggest that anal sensation is not a critical factor in preserving continence. This implies that the incontinence experienced after anorectal surgery or neuropathy cannot be explained by lack of anal sensation alone.

Adult↗
PubMed1981

The action of loperamide in inhibiting prostaglandin-induced intestinal secretion in the rat.

1 The mechanisms by which loperamide inhibits the intestinal secretion induced by prostaglandin E2 were investigated in rat jejunum. 2 In vivo loperamide prevented prostaglandin-induced fluid secretion but did not reduce the associated rise in the transintestinal potential difference. 3 In intestinal sheets the electrical response to prostaglandin E2 was enhanced in the presence of loperamide. 4 The ionic basis of these changes was determined by measuring Na+ and Cl- fluxes across intestinal sheets. Loperamide did not reduce the prostaglandin-induced increase in net Cl- secretion, although it prevented the inhibition of mucosal-to-serosal Na+ movement. 5 Loperamide does not alter cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels by a direct action at the enterocyte, since in isolated enterocytes neither basal nor prostaglandin-stimulated cyclic AMP levels were affected by the drug.

Animals↗
PubMed1981

Electrochemical detector for breath hydrogen determination: measurement of small bowel transit time in normal subjects and patients with the irritable bowel syndrome.

A method is described for the measurement of hydrogen in expired air, using an electrochemical detector. The apparatus is simple to use and sensitive. Its application is illustrated by studies of small bowel transit time made by measuring the time between oral ingestion of the unabsorbable carbohydrate lactulose and a rise in the concentration of hydrogen in expired air. In 20 control subjects transit time was 93.0 +/- 6.6 minutes, while in 16 patients with diarrhoea due to the irritable bowel syndrome it was 54.1 +/- 6.3 minutes (P less than 0.001), suggesting an abnormality in small intestinal motility in these patients. Loperamide, a potent antidiarrhoeal agent, increased transit time in 12 of these patients from 56.3 +/- 6.7 to 100.0 +/- 10.2 minutes (P less than 0.001).

Adolescent↗
PubMed1980

Chronic diarrhea of unknown origin.

We studied 27 patients with severe chronic diarrhea for which extensive investigations carried out at other institutions had failed to reveal a diagnosis. They were studied by standard diagnostic methods as well as by careful fecal analysis and intestinal perfusion. If they were incontinent of feces, anal sphincter function tests were performed. Although many were suspected of having pancreatic cholera syndrome, this diagnosis could not be established in a single patient. The most common diagnosis that could be established was surreptitious ingestion of drugs (laxatives in 7 patients and diuretics in 2). Other specific diagnoses included ulcerative colitis in 2 patients, allergy to beef in 1, and bacterial overgrowth of the small intestine in 1. Thus, we were able to establish a specific diagnosis in 13 patients. Of the remaining 14 patients, 8 had findings suggestive of irritable bowel syndrome, and 2 others had anal sphincter dysfunction as the major cause of their disability. The other 4 undiagnosed patients had severe secretory (3 patients) or osmotic (1 patient) diarrhea. Follow-up interviews at 6 mo-6 yr failed to reveal evidence of a cause for diarrhea that had been overlooked during our studies. The diagnostic approach to patients with unexplained diarrhea is discussed. The importance of a search for surreptitious drug ingestion and accurate measurement of bowel movement frequency and stool weight is emphasized.

Adult↗
PubMed1980

Transit of a meal through the stomach, small intestine, and colon in normal subjects and its role in the pathogenesis of diarrhea.

A method for measuring the transit time of a meal, containing sausages, mashed potato, baked beans, and a pineapple custard dessert, through the gastrointestinal tract was evaluated in 14 healthy volunteers. Gastric emptying was determined by incorporating a radioactive marker in the meal and counting over the surface of the stomach using a crystal scintillation detector. Small intestinal transit time was determined by measuring breath hydrogen excretion and by estimating the radioactivity over the cecum. Finally, whole gut transit time was measured by incorporating radiopaque plastic markers or carmine red in the meal and estimating the appearance of these markers in the stool. Our results showed that measurements of small intestinal transit time were reproducible and in the majority of subjects the increase in hydrogen excretion occurred at the same time as the increase in radioactive counts over the surface of the cecum. The passage of the first marker in the stool coincided with the appearance of carmine red. There were no significant correlations between small intestinal transit time and whole gut transit time or the half time for gastric emptying. Incorporation of 10, 25, and 40 g lactulose into our standard meal in place of sucrose increased the rate of transit through the small intestine but did not significantly alter the rate of gastric emptying or the whole gut transit time. Total stool weight for 48 hr after ingestion of the meal was inversely related to whole gut transit time but not to small intestinal transit time suggesting that the tendency to develop diarrhea in response to a meal containing unabsorbable carbohydrate depends more on the lack of colonic accommodation than on the rate of small intestinal transit. Finally, there was no significant correlation between the measurements of small intestinal transit time after a drink of lactulose and the transit time of a meal in the same subjects.

Adult↗
PubMed1979

Effect of ouabain on Na,K-ATPase and electrolyte transport in the dog ileum in vivo.

It is currently believed that the rate and direction of sodium transport in the small intestine may be regulated by the activity of Na,K-ATPase in the basolateral cell membrane. We tested this hypothesis by selectively infusing ouabain, a known inhibitor of Na,K-ATPase, into the mesenteric artery supplying a perfused loop of ileum in 18 dogs. Before ouabain infusion there were significant correlations between the activity of Na,K-ATPase and net and lumen to plasma fluxes of sodium and chloride. After ouabain, there was no significant change in sodium and chloride transport, unidirectional fluxes or transmucosal potential difference, despite a 50% reduction in Na,K-ATPase activity. Furthermore, there was no significant correlation between Na,K-ATPase activity and sodium or chloride transport after ouabain. The only statistically significant effect of ouabain infusion was a reduction in the rate of bicarbonate secretion. Thus, the results of our experiments suggest that mucosal Na,K-ATPase is not a rate-limiting step in the absorption of sodium and chloride in the dog ileum, though it may be an important facilitative factor.

Animals↗
PubMed1979

Spontaneous secretion from the dog small intestine in vivo.

Forty loops of small intestine in the dog were perfused under control conditions with a balanced electrolyte solution. Most of the loops absorbed sodium and water, but 10 loops were in a state of spontaneous intestinal secretion. Compared to absorbing loops, spontaneously secreting loops exhibited reduced values for lumen-to-plasma fluxes of sodium and chloride and increased values for the plasma-to-lumen fluxes of these ions. Analysis of flux ratios suggested that sodium and chloride were actively scecreted during spontaneous intestinal secretion in the dog. Spontaneous secretion was similar to the secretion induced by CT or VIP, except that the latter were associated with a change in PD whereas the PD in the spontaneously secreting loops was the same as in the spontaneously absorbing loops.

Animals↗
PubMed1979

The role of intraluminal junction potentials in the generation of the gastric potential difference in man.

Using flowing isotonic NaCl or flowing molar KCl electrodes, the magnitude of liquid junction potentials between the electrode tip and gastric juice was measured directly, and calculated from electrolyte concentrations in gastric juice according to standard formulas. Gastric transepithelial potential difference was obtained by subtracting the junction potential from the measured gastric potential difference. Junction potentials by direct experiment correlated closely with calculated values. The magnitude of the junction potential was shown to depend on the level of gastric acidity as well as on the nature of the flowing intraluminal electrode. However, transepithelial potential difference was always the same with the two electrode solutions. It is impossible to measure junction potentials with an intraluminal KCl agar electrode, but they must exist because these electrodes did not accurately measure transepithelial potential difference when gastric acidity was high. Pentagastrin caused a transient decline in transepithelial potential difference; this was not observed in patients with pernicious anemia. We conclude that accurate measurement of transepithelial potential difference must include correction for liquid junction potentials, which are sizable when gastric acidity is high. This can best be done with a flowing intraluminal electrode.

Achlorhydria↗
PubMed1979

Epidemic gastritis with hypochlorhydria.

Seventeen of 37 healthy volunteers participating in studies of acid secretion and 1 patient with Zollinger-Ellison syndrome became rapidly and profoundly hypochlorhydric. A mild illness with epigastric pain occurred in 9 subjects, usually several days before detection of hypochlorhydria. Gastric mucosal biopsy specimens taken from subjects during hypochlorhydria revealed severe fundal and antral gastritis; however, even when acid secretion was severely depressed, parietal cells were abundant and appeared normal histologically. During hypochlorhydria, gastric permeability to hydrogen, sodium, and lithium was normal in 4 subjects. Serum gastrin concentrations were usually normal, whereas serum pepsinogen concentrations were invariably elevated. Serum parietal cell antibodies were not present. Acid secretion returned to near baseline levels in 14 of 17 subjects after a mean of 126 days (range 53--235); severity of gastritis diminished concurrently in 7 of 10 subjects on whom biopsies were serially performed. An infectious etiology is suspected, although serologic studies and bacterial and conventional viral cultures of stool and gastric juice have not identified a candidate agent.

Achlorhydria↗
PubMed1978

Effect of modified sham feeding on jejunal transport and pancreatic and biliary secretion in man.

Because previous evidence suggested that intestinal secretion was under parasympathetic control, we investigated the effect of modified sham feeding on the intestinal transport of water and electrolytes by jejunal perfusion using a triple lumen tube. By measuring the concentration of amylase, protein, and bile acids entering the intestinal test segment, we were also able to obtain data on the influence of sham feeding on pancreatic and biliary secretion. Gastric contents were aspirated throughout the experiment. Although we observed a clear-cut cephalic phase of gastric acid secretion, sham feeding had no effect on jejunal transport of water and electrolytes or on the rate at which bile acids, protein, or amylase were secreted into the duodenum.

Adult↗
PubMed1978

Intestinal secretion induced by vasoactive intestinal polypeptide. A comparison with cholera toxin in the canine jejunum in vivo.

The effect of vasoactive intestinal polypeptide (VIP) on intestinal water and electrolyte transport and transmucosal potential difference was investigated in the dog jejunum in vivo and compared to secretion induced by cholera toxin. Isolated jejunal loops were perfused with a plasma-like electrolyte solution. VIP (0.08 mug/kg per min) was administered directly into the superior mesenteric artery by continuous infusion over 1 h. From a dye dilution method, it was estimated that a mean plasma VIP concentration of 12,460 pg/ml reached the loops. VIP caused secretion of water and electrolytes; for example, chloride: control, 8 mueq/cm per h absorption; VIP, 92 mueq/cm per h secretion. A marked increase in transmucosal potential difference (control, -1.0 mV; VIP, -5.9 mV, lumen negative) occurred within 1 min after starting VIP infusion. Analysis of unidirectional fluxes showed increased plasma-to-lumen flux of sodium and chloride and decreased lumen-to-plasma flux of sodium. Chloride and bicarbonate were actively secreted against an electrochemical gradient. Although sodium secretion occurred down an electrochemical gradient, flux ratio analysis suggested a component of active sodium secretion. VIP caused a slight increase in protein output into the loops; light microscopy revealed capillary dilatation and closed intercellular spaces. The effect of VIP was readily reversible. Except for the delayed onset of secretion, the effect of cholera toxin was qualitatively similar to VIP; however, capillary dilatation and increased protein output were not noted with cholera toxin.

Animals↗
PubMed1977

Dermatitis herpetiformis: effect of gluten-free diet on skin IgA and jejunal structure and function.

To clarify the controversy about the effectiveness of a gluten-free diet in dermatitis herpetiformis, 10 highly motivated patients were investigated. The indices used to assess improvement included deposition of sub-epidermal IgA in unaffected skin, counts of intraepithelial lymphocytes, deposition of IgA in jejunal villi, and electrical tests of glucose absorption. In every patient subepidermal IgA concentrations fell after gluten withdrawal. In all but one patient the dose of dapsone necessary to control symptoms was reduced. Indeed, six patients stopped taking the drug completely within a year. In nine patients biopsy specimens were taken from the jejunum; seven showed abnormalities in jejunal morphology, eight had increased numbers of intraepithelial lymphocytes, and five had increased numbers of IgA-reactive cells in the lamina propria. Two of these three indices improved after gluten withdrawal, which confirmed that all nine patients were adhering to their diet. Routine screening for malabsorption proved to be unsatisfactory for showing the mild jejunal disease found in patients with dermatitis herpetiformis. The electrical test of glucose absorption showed subnormal results in all eight patients tested, however, and in six the results improved after gluten withdrawal.

Adult↗
PubMed1977

Unstirred layer and kinetics of electrogenic glucose absorption in the human jejunum in situ.

Using an electrical technique we estimated the thickness of the unstirred layer in the human jejunum during kinetic studies of electrogenic glucose absorption. The unstirred layer in seven healthy volunteers (632 +/- 24 mum: mean +/- SEM) was significantly thicker than in 10 patients with active coeliac disease (442 +/- 23 mum) but not significantly different in seven patients who had responded to treatment by gluten withdrawal (585 +/- 49 mum). There were similar differences in the values of ;Apparent Km' for electrogenic glucose absorption between healthy control subjects (36 +/- 6 mM) active coeliac patients (11 +/- 1 mM) and treated coeliac patients (31 +/- 5 mM). The changes in PDmax however, showed a different pattern. The PDmax in the active coeliac group (6.8 +/- 0.7 mV) was lower than in controls (7.6 +/- 0.6 mV) but not significantly so, while the PDmax in the treated coeliac group (10.6 +/- 0.9 mV) was significantly higher than in both the active coeliac and control groups. It should be noted that both operational kinetic parameters obtained in the present study are much lower than those obtained previously (Read et al., 1976b) because of the use of siphonage. Analysis of the results using a computer simulation indicates that the reduction in Apparent Km in active coeliac disease can be caused by the interaction of the decreased maximal absorption rate for glucose (Jmax) with the attenuated unstirred layer. In these circumstances it is not necessary to postulate any change in the affinity of the transport mechanism for glucose (;Real Km'). It is remarkable that the disease process produces an Apparent Km which is much closer to the Real Km than that found in health.

Celiac Disease↗
PubMed1977

Relationship between changes in intraluminal pressure and transmural potential difference in the human and canine jejunum in vivo.

Recordings of transmural potential difference (PD) across the jejunum of conscious man in situ are characterised by spontaneous fluctuations of up to 10 mV. In 25 of 31 subjects (comprising seven normal controls and 24 patients under investigation for malabsorption, six of whom had coeliac disease) we observed a clear association between these fluctuations and changes in intraluminal pressure recorded at the same site. The most frequent PD changes were associated with type III pressure waves. These consisted predominantly of large waver (3-1 +/- 0-1 mV; mean +/- SEM, n = 317) which reached maximal amplitude approximately 45 seconds after the pressure peak and had a duration of 120 +/- 3 s, but also included less frequent spikes (0-5 +/- 0-1 mV; n = 110) concurrent with the pressure wave with a duration of 5 +/- 1 s. Although by recording at two sites in the jejunum 10 cm apart we were able to demonstrate that type III pressure waves appeared to be propagated aborally at a median rate of 60 cm per minute, the apparent rates of propagation of the corresponding PD waves were much more variable. The largest PD changes (7-8 +/- 0-4 mV; n = 19), lasting several minutes, were found in association with runs of type I waves (basic rhythm) superimposed on a type III wave. Both pressure and PD activities were suppressed by intramuscular propantheline bromide. Intraluminal pilocarpine caused a transient rise in PD not always accompanied by a change in pressure. Distention of the jejunum by rapid injection of a bolus of isotonic sodium chloride produced a delayed rise in the PD which could be prevented by prior administration of propantheline bromide. Experiments using Thirty-Vella loops of proximal jejunum in conscious dogs confirmed the effect of jejunal distension on the PD and also demonstrated that spontaneous retching is preceded by an increase in the PD. Consideration of these results in conjunction with data from other workers suggests the hypothesis that the larger spontaneous fluctuations in transmural PD in the jejunum of conscious man are caused by changes in electrogenic secretion associated with intestinal motility and mediated by cholinergic mechanisms. The possible association of increased secretory activity with motility may have functions of lubrication as well as diluting and mixing the chyme for easier digestion and absorption.

Animals↗
PubMed1977

Electrical assessment of functional lactase activity in conscious man.

Using an electrical technique for measuring transjejunal potential differences (PDs) in conscious man, we have estimated the electrogenic absorption of the hexoses liberated by hydrolysis of lactose which was infused into the jejunum of one normal control and 21 patients with diarrhoea. The results were compared with jejunal lactase levels determined from biopsy specimens taken from the recording site immediately after infusion. The PD evoked by 100 mM lactose was very significantly lower in patients with lactase levels below 4 units (lactase deficient) compared with subjects with normal lactase levels. There was also a significant correlation (r = 0.87, P less than 0.005) between the magnitude of the lactose potential (expressed as the ratio of the maximum glucose transfer potential) and the mucosal lactase level in the hypolactasic subjects but not in patients with normal lactase levels. Thus, in the subjects with lactase deficiency, the electrogenic transfer of hexose is clearly limited by the rate of lactose hydrolysis. Unlike other assessments of functional lactase activity, the electrical test provides a specific index of jejunal function and, moreover, can be adapted to investigate the possible disorders of small intestinal motility and secretion associated with hypolactasia.

Adolescent↗