Search PubMedSearch

Biomedical subjects

B Creamer

Publications and source records attributed to B Creamer.

At least 19 recordsLinked to original sources

Simultaneous administration of lactulose and 51Cr-ethylenediaminetetraacetic acid. A test to distinguish colonic from small-intestinal permeability change.

In normal adults intestinal permeation of ingested 51Cr-ethylenediaminetetraacetic acid (EDTA) is greater than that of lactulose. This difference is abolished in patients with ileostomies, suggesting that it results from colonic permeation of 51Cr-EDTA, which, unlike lactulose, resists bacterial degradation. To investigate the effect of an increase in colonic permeability on absorption of the two molecules, lactulose (5 g) and 51Cr-EDTA (50 microCi) were given orally in isosmolar solution to 11 patients with colitis, and their 24-h urinary excretion measured. By comparison the effect of an increase in small-intestinal permeability induced by ingestion of a hyperosmolar solution (4240 mosm/l) was measured in 10 healthy adults. Hyperosmolar stress increased the 24-h urinary excretion of 51Cr-EDTA above the normal mean + 2 standard deviations (3.31%) in all 10 healthy subjects, and in all of these excretion of lactulose was also increased (greater than 1.06%). In contrast, although seven colitics had a urinary excretion of 51Cr-EDTA above the normal mean + 2 SD, in only two of these patients was recovery of lactulose increased. This suggests that simultaneous administration of lactulose and 51Cr-EDTA may enable permeability changes affecting the colon alone to be distinguished from those involving the small intestine.

Adult

Do non-steroidal anti-inflammatory drugs increase colonic permeability?

Urinary excretion of orally administered lactulose and 51 chromium labelled ethylenediamine tetra-acetate (51Cr-EDTA) was measured in 12 healthy adult subjects and in six patients with ileostomies to assess intestinal permeability. In normal subjects, 24 hour urinary recovery of 51Cr-EDTA was significantly greater than that of lactulose (mean (SEM) 2.27 (0.15) v 0.50 (0.08)% oral dose; p less than 0.001), but in ileostomy patients recovery of the two markers was the same. In normal subjects, therefore, the difference between the two markers may arise from bacterial break-down of lactulose but not of 51Cr-EDTA in the distal bowel, urinary excretion of lactulose representing small intestinal permeation and that of 51Cr-EDTA representing both small and large intestinal permeation. The markers were then given simultaneously to nine patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) for rheumatoid arthritis and osteoarthritis. The 24 hour urinary recovery of 51Cr-EDTA in the patients was significantly greater than normal (4.64 (1.20) v 2.27 (0.15)% oral dose; p less than 0.01), but that of lactulose was not significantly affected. Moreover, the increase in 51Cr-EDTA recovery was most noticeable in the later urine collections. Both of these findings suggest that NSAIDs may increase colonic permeability.

Adult

Acute colorectal ischaemia after anaphylactoid shock.

A 29 year old woman is reported with bloody diarrhoea three hours after developing anaphylactoid shock. Sigmoidoscopy, barium enema, and histology showed rectal and colonic ischaemia to the splenic flexure. Recovery was complete. There was no history of vascular disease but the patient was taking an oral contraceptive. Thirty one other cases of spontaneous ischaemic proctitis are reviewed.

Acute Disease

The effect of poorly absorbed solute on intestinal absorption.

To determine the effects of poorly absorbed solute on intestinal absorption, the urinary recovery of ingested lactulose, L-rhamnose, D-xylose, and 3-O-methyl-D-glucose was measured after simultaneous ingestion of various 'loads' of mannitol given in iso-osmolar solution. Mannitol reduced intestinal uptake of the poorly absorbed test sugars, lactulose and L-rhamnose; uptake of D-xylose and 3-O-methyl-D-glucose, which are absorbed by carrier-mediated transport largely from the jejunum, was less affected. The dose-response effect of mannitol on the absorption of L-rhamnose was approximately exponential; doses of 5, 10, and 20 g mannitol reduced the average urinary excretion of L-rhamnose by 34.7%, 51.7%, and 61.2%, respectively. In this respect, an osmotically equivalent load of lactulose, ingested as 'solute', was approximately twice as effective as mannitol in reducing L-rhamnose absorption, probably because lactulose is more poorly absorbed than mannitol (less than 1.0% versus 32-41%). Ingestion of other poorly absorbed solutes such as raffinose, sorbitol, xylitol, magnesium sulphate, and sodium sulphate also significantly depressed the absorption of L-rhamnose; in contrast, more efficiently absorbed solutes, such as sodium chloride, glucose, glycerol, and urea had little effect.

3-O-Methylglucose

Abnormal intestinal permeability to sugars in villous atrophy.

Intestinal permeability to a monosaccharide and a disaccharide was compared by simultaneous measurement of the urinary excretion of L-rhamnose and lactulose after oral ingestion of an hypertonic solution containing both sugars. Urine samples were analysed for sugar content by quantitative thin-layer or paper chromatography. Results in thirteen patients with untreated villous atrophy were compared with those in twelve healthy volunteers. Urinary L-rhamnose excretion was significantly decreased (-40%, p less than 0.02) in patients with villous atrophy, whereas lactulose excretion was paradoxically and significantly increased (+345%, p less than 0.01). The median value of the lactulose/L-rhamnose urinary excretion ratio was sevenfold higher in the patients with villous atrophy; there was no overlap of values for patients and volunteers (p less than 0.01). It is postulated that reduced L-rhamnose urinary excretion in untreated villous atrophy is due to a decreased absorptive area in the small bowel, whereas increased lactulose excretion indicates leakiness of the abnormal mucosa to larger polar molecules.

Adult

Osteomalacia after small-intestinal resection.

Histological examination of bone from 25 patients with small-intestinal resection showed that 9 (36%) had osteomalacia, which was severe in 5 and mild in 4. The serum-alkaline-phosphatase concentration was raised in all patients with severe osteomalacia, but serum calcium, phosphate, and alkaline-phosphatase concentrations were normal in the 4 patients with mild disease, 2 of whom had symptoms. Osteomalacia was diagnosed radiologically in only 3 patients. Osteomalacia appears to be commoner in patients with small-intestinal resection than has previously been thought, and bone biopsy is essential if all cases are detected. Although high-dose parenteral vitamin-D therapy is usually effective in the treatment of osteomalacia after small-intestinal resection, our findings showed that oral vitamin-D metabolites and their analogues may also be effective. This has important practical advantages.

Administration, Oral

Effect of hyperosmolar stimuli and coeliac disease on the permeability of the human gastrointestinal tract.

1. Oral loads have been used to assess the permeability of the human gastrointestinal tract, with lactulose (mol. wt. 342), raffinose (mol. wt. 504), stachyose (mol. wt. 666) and a fluoresceinlabelled dextran (mol. wt. 3000) as marker substances. Timed urinary recovery of these substances, which are not metabolized, was measured by quantitative paper chromatography and direct fluorimetry, and the results were used as an indication of passive intestinal permeability. 2. Results in healthy adults showed that permeability to these markers was dependent on molecular size, even after correction for aqueous diffusion differences, such that a profile of restricted permeability could be described for this range of markers. Interpretation in terms of conventional pore theory suggested the presence of more than one population of pores. 3. Ingestion of solutions made hyperosmotic by inclusion of glycerol resulted in a large increase in permeability, in a pattern that suggested an increase in either the size or frequency of a range of smaller pores. 4. A similar increase in permeability and alteration in the profile of restriction was found in patients with coeliac disease. 5. The possible location of such pores in the gastrointestinal mucosa is discussed in relation to the cell membrane, the intercellular junction, and the sites of cell exfoliation.

Celiac Disease

Asthma and extrinsic allergic alveolitis due to Merulius lacrymans.

A teacher with breathlessness of insidious onset developed acute symptoms on return home following his discharge from hospital. His flat was found to have extensive dry rot (Merulius lacrymans). Precipitins and specific IgE and IgG antibody against M. lacrymans were present and intracutaneous testing gave a typical dual skin reaction. Pulmonary physiology demonstrated airflow obstruction with a low DLCO and KCO, and a chest X-ray showed diffuse micronodular shadowing, maximal in the mid-zones. Inhalation challenge testing provoked a combined asthmatic reaction without a change in DLCO. Rapid clinical recovery and more gradual radiographic and physiological improvement followed cessation of exposure to the antigen.

Adult

Plasma levels and intestinal absorption of 25-hydroxyvitamin D in patients with small bowel resection.

Plasma levels of 25-hydroxyvitamin D (25-OHD) were found to be significantly reduced in a group of patients with small bowel resection when compared with normal controls. Plasma levels of 25-OHD after an oral dose of 25-hydroxyvitamin D3 (25-ohd3) were also reduced in the patient group. Dietary intake of vitamin D tended to be low in many patients, but seasonal variation of plasma 25-OHD levels indicated normal exposure to sunlight in most of the patients studied. It is suggested that these studies provide some evidence for malabsorption of 25-OHD after small bowel resection, which, it is postulated, may be due to interruption of the enterohepatic circulation of bile acids and of 25-OHD. These factors may contribute towards the low plasma levels of 25-OHD found in the patient group.

Adult

The exsorption characteristics of various sugars.

Various sugars were administered intravenously to rabbits and the rate of exsorption from plasma to intestinal lumen was measured. The exsorption rates of lactulose, mannose, and xylose were directly related to their plasma concentration but varied according to their molecular weight. Wglucose and galactose did not appear in the intestinal lumen until very high plasma concentrations were reached. The mucosal barrier which prevented glucose and galactose exsorption was abolished when luminal phlorizin M times 10-minus 2 or another actively absorbed sugar was placed in the lumen. 2:4 Dinitrophenol M times 10-minus 3 and the absence of the sodium ion did not impair the ffficiency of the barrier. When the plasma glucose concentration was raised to very high levels, glucose began to appear in the lumen; further increases in the glucose concentration then produced a rapid exsorption of glucose.

Animals

Hyperphagia in intestinal disease.

Six patients with hyperphagia (ingestion of 5-11 000 Kcals/day) associated with severe malabsorption and steatorrhoea are described. The cause of the malabsorption was coeliac disease in three patients, Crohn's disease with ileal resection in two, and carcinoma of the pancreas in one patient. There was no evidence of neurological or endocrine disease (apart from mild diabetes mellitus in the patient with carcinoma of the pancreas) but three patients suffered from severe depression. This association may be commoner than previously realized and be revealed in patients with steatorrhoea of unexplained severity by careful dietary assessment. Its detection has therapeutic implications since restriction of caloric and fat intake decreased steatorrhoea without weight loss in several of the patients described.

Adult