Orocaecal Transit Research Articles

Adaptation and effects of ileal reservoir on ileo-proctostomy following total colectomy in dogs

We examined postoperative adaptation and effects of J-pouch reservoir on ileo-proctostomy following total colectomy in dogs. End to end (E-E; n = 5) or J-pouch (J-P; n = 5) anastomosis was performed after resection of total colon and the rectum 3 cm above the peritoneal reflexion. Gastrointestinal motility with strain gauge force transducers (SG) and transit time with barium meal under the fluoroscopy were recorded 6 months after total colectomy. Then, histological changes of seven specimens from totally resected ileum in J-P and E-E vs control (normal ileum; n = 5) were measured with hematoxylin-eosin and PYY immunohistochemical stains. Propagation rate of interdigestive migrating complex (IMC) from jejunum to ileum was significantly lower in J-P (64.8 +/- 13.2%) than in E-E (98.6 +/- 1.2%) (p < 0.001). Oro-neorectal transit time (ONTT) in E-E (138 +/- 10 min) was shorter (p < 0.05), but ONTT in J-P (189 +/- 26 min) was significantly longer (p < 0.01) than oro-caecal transit time (OCTT) in preoperative control (165 +/- 19 min; n = 10). There was no difference about length of villi among control, E-E and J-P, but length of crypts in J-P (0.59 +/- 0.08 mm) was longer than that in E-E (0.27 +/- 0.02 mm) and normal ileum (0.34 +/- 0.07 mm) (p < 0.01). PYY positive cells in J-P were more than in E-E and control at any site of ileum and total number of PYY positive cells in J-P (168 +/- 18) significantly increased than that in E-E (111 +/- 16) and control (103 +/- 14) (p < 0.05). Thus, increase of PYY positive cells in J-P inhibits gastrointestinal motility and transit. Delayed transit time and crypts elongation were intestinal adaptation that assists the absorption of luminal contents. Therefore, it suggested that J-pouch reservoir had advantage to ileo-proctostomy following total colectomy in dogs.

Small Intestinal Permeability and Orocaecal Transit Time in Elderly Patients with Cardiac Cachexia

Small Intestinal Permeability and Orocaecal Transit Time in Elderly Patients with Cardiac Cachexia

Decreased orocaecal transit time, as measured by the exhalation of hydrogen, in hyperthyroid cats

Orocaecal transit time was assessed in healthy cats and cats with hyperthyroidism by means of the breath hydrogen test using a standard liquid meal with lactulose. The median transit time in 10 healthy cats was 98 minutes (range 60 to 150 minutes) and 90 minutes (range 75 to 150 minutes) in a repeated assessment. The median transit time in 10 cats with hyperthyroidism was 53 minutes (range 45 to 150 minutes) which was significantly more rapid (P<0·05) than in the healthy cats.

Orocaecal transit time in patients with Crohn disease.

Orocaecal transit time (OCTT) using the lactulose hydrogen breath test was investigated in 16 patients (age 10-19.4 years) with active Crohn disease (CD). Disease activity was assessed by the paediatric CD activity index (PCDAI). OCTT was prolonged in all patients (mean 149.9 min, SD 32.7) relative to healthy age-matched controls (mean 56.9 min, SD 11.1). PCDAI was increased (median 48.8, range 32.5), indicating moderate to severe disease in all patients. A close correlation between OCTT and PCDAI (Spearman r = 0.90) was observed. Following nutritional therapy with a semi-elemental diet over a period of 6 weeks OCTT and PCDAI declined, OCTT becoming normal in 4 and PCDAI in 4/12 patients respectively. OCTT provides a sensitive, non-invasive method for the assessment and followup investigations in patients with CD.

Oro-caecal transit time in man assessed by the sulfasalazine/sulfapyridine test. Correlation between plasma-saliva appearance of sulfapyridine.

Oro-caecal transit time in man assessed by the sulfasalazine/sulfapyridine test. Correlation between plasma-saliva appearance of sulfapyridine.

Non-invasive assessment of gastrointestinal motility disorders in diabetic patients with and without cardiovascular signs of autonomic neuropathy.

Twenty six patients with insulin dependent diabetes mellitus underwent a gastric emptying test, a gall bladder contraction test, an orocaecal transit study, and a colon transit test. Eleven patients had signs of cardiovascular autonomic neuropathy, 15 patients were without signs of cardiovascular autonomic neuropathy. Mean gastric clearance of radioopaque markers ingested with a meal averaged 29.5 (2.3) markers per six hours in subjects without cardiovascular autonomic neuropathy compared with 17.8 (2.3) markers per six hours in patients with cardiovascular autonomic neuropathy (p < 0.02). Gall bladder emptying in response to graded CCK8 stimulation was impaired in five of 11 patients with cardiovascular autonomic neuropathy, whereas it was normal in the patients without cardiovascular autonomic neuropathy (p < 0.01). Oral caecal transit times were not significantly different in the two patient groups, whereas colonic transit was slower in the patients with cardiovascular autonomic neuropathy compared with the group without cardiovascular autonomic neuropathy (p < 0.02). There was no correlation between disturbed gastric clearance, impaired gall bladder contraction, and prolonged colonic transit time in the patients with cardiovascular autonomic neuropathy nor was there a correlation between any disturbed motor function and age or duration of diabetes. It is concluded that autonomic neuropathy can affect motor functions throughout the gastro-intestinal tract. Any disturbed motor function in the gut could therefore be one of the numerous expressions of diabetic neuropathy affecting the cardiovascular, the endocrine or the gastrointestinal system.

The influence of gastrointestinal transit on drug absorption in healthy volunteers.

1. The effect of variability of gastric emptying and oro-caecal transit on the absorption of a multicomponent solution of frusemide, atenolol, hydrochlorthiazide and salicylic acid has been studied in six healthy subjects. Each subject was studied on five separate occasions: three times under basal conditions, once following metoclopramide and once following codeine pretreatment in an attempt to speed and slow transit respectively. 2. Inter-subject variability of gastric emptying, oro-caecal transit and the rate and extent of drug absorption was considerable. 3. The absorption of salicylic acid appeared rate-limited by gastric emptying but the rate and extent of frusemide, atenolol and hydrochlorthiazide absorption were unrelated to measures of gastric emptying or oro-caecal transit. 4. Codeine phosphate caused a two-fold delay in oro-caecal transit but did not influence gastric emptying while metoclopramide had no significant effect on either function. 5. Metoclopramide and codeine had no significant effect on the rate or extent of absorption of any of the study drugs. 6. Within the limits of this experiment, oro-caecal transit time did not appear to be an important determinant of frusemide, atenolol, hydrochlorothiazide or salicylic acid absorption. Other factors must account for the observed variability in drug absorption.

Effects of a non-absorbable osmotic load on drug absorption in healthy volunteers.

1. We have studied the effects of a non-absorbable osmotic load on the absorption of a multicomponent solution of frusemide, atenolol, hydrochlorothiazide and salicylic acid in six healthy volunteers. 2. Each subject was studied on up to four separate occasions. The drugs were administered in one of four solutions: a) a mannitol/electrolyte solution, b) a double-strength mannitol/electrolyte solution, c) a glucose/electrolyte solution and d) water. Lactulose or sulphasalazine were added as oro-caecal transit markers. Lactulose was included in the mannitol- and glucose-based solutions, adding a further non-absorbable osmotic load, and sulphasalazine was added to the water, adding little osmotic load. 3. The absorption of atenolol and hydrochlorothiazide was two- to three-times less from all lactulose-containing solutions than from the sulphasalazine-containing solution. The absorption of frusemide and salicylic acid was similar from all four solutions. 4. The largest non-absorbable osmotic load impaired the absorption of atenolol and hydrochlorothiazide most and the incorporation of glucose only partly restored absorption. 5. These results suggest that transmucosal water movement is an important determinant of atenolol and hydrochlorothiazide absorption but is less relevant for the absorption of frusemide and salicylic acid. Furthermore, these data demonstrate a previously unrecognised interaction between a commonly prescribed laxative--lactulose, and atenolol and hydrochlorothiazide.

The effect of chilli on gastrointestinal transit.

The effects of chilli on gastrointestinal transit (gastric emptying, orocaecal transit, whole gut transit) were evaluated in eight healthy volunteers. In each subject, gastrointestinal transit of a standard test meal was measured on two separate days. On one of these occasions, 20 g of chilli powder was added to the meal. Gastric emptying was quantified with a radioisotopic technique, orocaecal transit by measurement of breath hydrogen concentrations and whole gut transit by counting the number of radio-opaque markers in the stool. The rate of gastric emptying was slower (P less than 0.05) and whole gut transit was faster (P less than 0.02) after the meal containing chilli, compared with the other meal. There was no significant difference in orocaecal transit. These results show that ingestion of chilli is associated with significant effects on gastric emptying and intestinal transit.

The effect of sleep on the gastrointestinal transit of pharmaceutical dosage forms

The gastrointestinal (GI) transit of pharmaceutical dosage forms was studied during sleep in eight, healthy, male volunteers. Each ingested five 7-mm radiolabelled tablets and a pressure-sensitive radiotelemetry capsule (RTC) following a light meal on two separate occasions, administered either at night (22:00) or in the morning (08:00). Transit of the tablets was monitored by gamma scintigraphy and the RTC detected contractile activity within the GI tract. Oro-caecal transit of the 7-mm tablets was longer for night-time dosing compared to morning administration, although the difference did not reach statistical significance. Gastric residence time and small intestinal (SI) transit time of the RTC were also extended after night time dosing. Total transit times of the RTC were similar following both morning and night-time administration. These results may be explained by alterations in the periodicity of the fasting migrating myoelectric complex (MMC) at night.

The effect of thyroxine on small intestinal motility in the elderly

To study the effects of thyroxine on orocaecal transit time in a group of elderly hypothyroid patients on long-term thyroxine replacement therapy. Measurement of the effect of withdrawal and subsequent replacement of thyroxine replacement therapy on orocaecal transit time. Fifteen elderly, previously hypothyroid patients on full replacement therapy with oral thyroxine were studied. There were 11 females and four males, aged 60-94 years (median 78 years) receiving initially 50-200 micrograms of oral thyroxine daily (median 100 micrograms). Serum TSH and FT4 were measured by radioimmunoassay and orocaecal transit time assessed using a lactulose hydrogen breath test. These tests were repeated 7 days after withdrawal of thyroxine replacement and again 7 days after subsequent reinstatement of therapy. On withdrawal of therapy, the median transit time increased from 75.0 to 135 minutes (P less than 0.01), the median TSH increased from 1.8 to 2.3 mU/l (P = NS) and the median FT4 decreased from 13.7 to 10.6 pmol/l (P less than 0.01). On reinstatement of therapy, the median transit time decreased to 95 minutes (P = NS), the median TSH decreased to 1.1 mU/l (P = NS) and the median FT4 increased to 14.1 pmol/l (P less than 0.01). These findings demonstrate the sensitivity of the small bowel to changes in thyroid hormone status and suggest that constipation arising as a result of this hypomotility may well be an early physical manifestation of hypothyroidism.

Dietary fibre effects on intestinal transit in man: involvement of their physicochemical and fermentative properties

In order to study the mechanism of the dietary fibre action on the intestinal transit in man, the chemical nature together with the physicochemical and in vitro fermentative properties of five fibres were evaluated and then related to the effects of the latter on the orocaecal transit time (OCTT) and the orofaecal transit time (OFTT) in healthy volunteers. The results showed that the fibre water-binding capacity might be involved in the OCTT and an increase was observed with a fibre-supplemented diet. The fibres, which were capable of decreasing the OFTT, could act by a mechanical effect if they were not fermented in vitro. However, the partly degradable fibres might also change the OFTT via their products of fermentation. A large production of propionic and butyric acids, in particular, could be responsible for the effects of some fibres on the intestinal transit.

Modulation of orocaecal transit time by hypnosis.

The ability of hypnosis to modulate the orocaecal transit time of 10 g lactulose was tested in six healthy volunteers. Orocaecal transit time was measured by the hydrogen breath test during three periods in random order. During the control period the subjects remained throughout the test in a semirecumbent position without moving. During the hypnotic relaxation period subjects were hypnotised before lactulose ingestion and were instructed to experience relaxation till the orocaecal transit time had elapsed. During the acceleration suggestion period subjects were hypnotised before lactulose ingestion and were repeatedly instructed to imagine the acceleration of lactulose through the intestine until transit time had elapsed. The mean orocaecal transit time was significantly longer during the hypnotic relaxation period (mean (SEM) 133 (8) min) than during the control period (93 (13) min). The mean orocaecal transit time during the acceleration suggestion period was 105 (26) minutes and was not significantly different from the mean transit time during the control period. The individual values during the acceleration suggestion period were scattered. We conclude that lactulose orocaecal transit time is delayed during hypnotic relaxation.

Orocaecal transit time in Duchenne muscular dystrophy.

Smooth muscle degeneration may occur in Duchenne muscular dystrophy. We measured fasting orocaecal transit time in patients with advanced Duchenne muscular dystrophy and other muscular dystrophies and in healthy controls. No significant differences were found. In contrast to reports of gastric hypomotility in Duchenne muscular dystrophy, we found no evidence of impaired small intestinal motility.

Scintigraphic Determination of Gastrointestinal Transit Times: A Comparison with Breath Hydrogen and Radiologic Methods

A scintigraphic method for determination of gastrointestinal transit times was compared with the breath hydrogen test and a multiple-bolus, single-radiograph technique. A close temporal association was found between the caecal appearance of radioactivity and the onset of breath hydrogen excretion in eight healthy subjects. Neither mean small-intestinal nor mean orocaecal transit times of the radiolabelled marker were correlated with the magnitude of hydrogen peak, hydrogen peak time, or the area under hydrogen curve. No correlation was noted between whole-gut transit time of the radiolabelled marker and mean whole-gut transit time calculated from a 6-day administration of the radiopaque marker in 16 healthy subjects. The stool weight was inversely correlated with the mean colonic (r = -0.46, p = 0.009) and the mean whole-gut (r = -0.45, p = 0.011) transit times of the radiolabelled marker. In conclusion, inadequate delineation of the caecal region seems to be an unimportant drawback of the scintigraphic measurements, whereas day-to-day variation in gastrointestinal transit rates may influence the reliability of the assessments. Probably, quantitative transit data cannot be obtained from the breath hydrogen concentration profiles.

Effect of erythromycin on the oro-caecal transit time in man

Erythromycins often cause gastrointestinal side-effects due to an increase in motility or to change in the intestinal bacterial flora. In order to evaluate the effect of erythromycin on gastrointestinal motility. 11 healthy volunteers were given placebo, erythromycin stearate (ES) 1000 mg or a therapeutically equivalent single dose of erythromycin acistrate (EA.2'-acetyl erythromycin stearate) 800 mg in a double-blind trial. The oro-caecal transit time was measured using the hydrogen breath test with lactulose as the substrate. The transit time was estimated from the H2-peak (ppm) in end-expiratory breath by two methods, t1 representing the "front" and t2 the "bulk" of lactulose reaching the colon. t1 was 51 min in the placebo group, 38 min in the EA and 31 min in the ES group (p less than 0.05, ES vs placebo). t2 was 74 min, 64 min, and 46 min, respectively (p less than 0.05, ES vs placebo). The difference between EA and ES was also significant. Six subjects in the ES group but none in the EA group recorded adverse gastrointestinal effects attributable to medication. It was concluded that erythromycin shortens the oro-caecal transit time in man and that EA effects the transit time slightly less than ES.

Effect of the microbial lactase (EC 3.2.1.23) activity in yoghurt on the intestinal absorption of lactose: An in vivo study in lactase-deficient humans

Breath hydrogen excretion was measured in eight lactase (EC 3.2.1.108)-deficient volunteers ingesting 18 g lactose in the form of milk, yoghurt and heated yoghurt. Total excess hydrogen excretion (area under curve) was significantly lower after yoghurt and heated yoghurt, than after milk: 103 (SE 29), 191 (SE 32), and 439 (SE 69) respectively (P less than 0.001). The oro-caecal transit time of fermentable components from yoghurt and heated yoghurt (mainly lactose) was longer than that from milk: 165 (SE 17), 206 (SE 19), v. 103 (SE 19) min (P less than 0.01). An intestinal perfusion technique was used in the same subjects after ingestion on two consecutive days of 18 g lactose in yoghurt and heated yoghurt. Significantly less lactose was recovered from the terminal ileum after yoghurt than after heated yoghurt meals: 1740 (SE 260) v. 2825 (SE 461) mg (P less than 0.05), and approximately one-fifth of the lactase activity contained in yoghurt reached the terminal ileum. These findings indicate that more than 90% of the lactose in yoghurt is digested in the small intestine of lactase-deficient subjects and suggest that both the lactase activity contained in the viable starter culture and a slow oro-caecal transit time are responsible for this excellent absorption.

Small intestinal permeability and orocaecal transit time in cystic fibrosis.

Cellobiose and mannitol were used as probe molecules to measure intestinal permeability in 36 children with cystic fibrosis, and 25 age matched controls. Orocaecal transit was also evaluated for each subject using the lactulose/hydrogen breath test. There was a fourfold increase in permeability to disaccharide (cellobiose) in patients with cystic fibrosis, but permeability to the monosaccharide (mannitol) was similar to controls. The orocaecal transit time of lactulose was prolonged in patients with cystic fibrosis, but was unrelated to the percentage excretion of cellobiose or mannitol in cystic fibrosis patients or control subjects.

GI transit of potential bioadhesive systems in the rat

The oral availability of a drug may be limited by the residence time of the dose in the upper GI tract. Among the methods proposed to delay the transit of oral pharmaceutical formulations is the use of bioadhesion. The GI transit of four potential bioadhesive polymers, presented in a number of different formulations, was investigated in the rat. Formulations were dosed orally, and GI transit was assessed by killing animals at various intervals and sectioning the GI tract. Significant differences in oro-caecal transit were obtained with certain formulations, with 4% and 5% solutions of Carbopol 934 showing delays of 25% in transit to the ileo-caecal junction.

GI transit of potential bioadhesive formulations in man: A scintigraphic study

It is known that the oral availability of certain drugs can be limited by the residence time of the dose in the upper GI tract. Among the methods proposed to delay the transit of oral pharmaceutical formulations is the use of bioadhesion. In this work, the gastric emptying and small intestinal transit of some potentially adhesive formulations were studied in man by gamma scintigraphy. Two different capsule formulations were investigated, in combination with two potentially bioadhesive polymers and a non-adhesive control. Small differences in oro-caecal transit were seen with certain combinations, but no dramatic effects on GI transit were observed.