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Biomedical subjects

I Cobden

Publications and source records attributed to I Cobden.

52 records · Page 3Linked to original sources

The acute effects of ethanol on acetanilide disposition in normal subjects, and in patients with liver disease.

1 The effects of single doses (25 g and 50 g) oral ethanol on the disposition of acetanilide (50 mg/kg metabolic active mass) has been studied in normal subjects, and in patients with chronic non-alcoholic liver disease. 2 In normal subjects, ethanol produced a dose-dependent increase in acetanilide half-life, and a decrease in acetenilide clearance. There was a significant correlation (rs = 0.71, P less than 0.01) between the 90 min blood ethanol concentration and the reduction in acetanilide clearance. 3 In patients with liver disease, ethanol produced a similar proportional change in acetanilide half-life and clearance, but these were less consistent. Moreover, liver disease itself was associated with an increase in acetenilide half-life, and a reduction in clearance. 4 It is concluded that single oral doses of ethanol, comparable to those consumed during social drinking, may inhibit some forms of microsomal oxidation and thus have important clinical implications.

Acetanilides↗

Simultaneous culture of saliva and jejunal aspirate in the investigation of small bowel bacterial overgrowth.

Both saliva and jejunal aspirate were cultured from 22 patients with suspected small bowel bacterial overgrowth and from eight controls. Large numbers of organisms (greater than 10(6)/ml) were recovered from the jejunal aspirate of 16 subjects, in five of whom the same organisms were present in similar relative proportions in the saliva, suggesting contamination of the sample with saliva, while in 11 the jejunal organisms differed from those in saliva. In eight of these the jejunal flora was a typical 'faecal' flora usually associated with small bowel bacterial overgrowth but, in three, the jejunal floral was superficially similar to that of saliva. Distinct subpopulations of bacteria, typically Gram-positive non-sporing rods, were, however, evident in the jejunum of these patients, and were also recovered, in smaller numbers, from the jejunum of controls, suggesting that they form a distinct jejunal microflora. Culture of saliva in addition to jejunal aspirate may be useful in the recognition of contamination of the proximal small bowel with saliva, and in the diagnosis of small bowel bacterial overgrowth.

Bacteria↗

Intestinal permeability in coeliac disease: the response to gluten withdrawal and single-dose gluten challenge.

Intestinal permeability has been studied in 21 patients with coeliac disease in relapse and after gluten withdrawal using an oral test of intestinal permeability based on the simultaneous oral administration of two probe molecules. The increased absorption of the larger molecule (cellobiose) and the decreased absorption of the smaller (mannitol) found in untreated coeliac disease both returned to normal within five months of starting treatment, the abnormality in cellobiose absorption correcting more rapidly than that of mannitol. After exposure to a single oral dose of gluten, the intestinal permeability of six patients with treated coeliac disease became transiently abnormal with an increased absorption of cellobiose, returning to normal within one week. The possible structural and functional implications of these findings are discussed. The cellobiose/mannitol ratio appears to be of value in assessing the response to gluten withdrawal in coeliac disease, and also in monitoring patients who are already established on a gluten free diet by detecting dietary lapses and 'non-responding coeliac disease'. It may also offer an alternative to jejunal biopsy in patients subjected to gluten challenge.

Adolescent↗

Passive permeability in experimental intestinal damage in rats.

1. Experiments were performed to study the absorption of two simultaneously administered polar probes of different molecular size from closed intestinal loops in rats subjected to various mucosal structural lesions. 2. Absorption of mannitol (molecular radius approximately 0.40 nm) was significantly decreased in rats with villous atrophy and crypt hypoplasia induced by the cytostatic agent methotrexate. The absorption of lactulose (radius approximately 0.54 nm) was also decreased, in contrast to the increased absorption which was found in an earlier study when villous atrophy with crypt hyperplasia was induced by infection by a nematode. The effect of local damage to villous tips, produced by the intraluminal presence of a detergent, was to increase significantly the absorption of lactulose. 3. In conjunction with the findings of earlier studies, these results support the hypothesis that there are at least two routes for the permeation of polar molecules. Small molecules such as mannitol probably pass through numerous cellular pores with a maximum radius lying between 0.40 and 0.54 nm and absorption is closely related to mucosal surface area. Larger molecules such as lactulose are probably restricted to less numerous extracellular pathways and absorption may be related to cell shedding or other areas of mucosal damage.

Animals↗

Pancreatic exocrine function in systemic sclerosis.

Lundh tests of pancreatic exocrine function were performed on twenty unselected patients with systemic sclerosis. Three patients had very low levels of tryptic activity in their intestinal juice and only nine had results which were unequivocally normal. Eight patients had biochemical steatorrhoea, but in six this was associated with intestinal bacterial overgrowth and a seventh had primary biliary cirrhosis. The remaining patient had no cause for steatorrhoea other than the marked pancreatic insufficiency which had been demonstrated. Although pancreatic damage may contribute to malabsorption in systemic sclerosis, it appears to be less important than other factors such as intestinal bacterial overgrowth.

Adolescent↗

Double-blind clinical, endoscopic and histological comparison of hydrotalcite/dimethicone suspension and magnesium hydroxide/aluminum hydroxide suspension in the treatment of symptomatic gastritis.

A double-blind, randomized trial was undertaken to compare the clinical, endoscopic and histological response to 6-weeks' treatment with hydrotalcite/dimethicone suspension or magnesium hydroxide/aluminum hydroxide suspension in 36 patients with symptomatic gastritis. Significantly more patients (P less than 0.05) showed symptomatic improvement in the antacid-treated group than in the hydrotalcite/dimethicone-treated group and more had a reduction in histological inflammatory scores (P less than 0.01), although there was little correlation between histology and symptoms. There was no evidence from this study that the bile acid binding and anti-foaming properties of hydrotalcite/dimethicone suspension were of any benefit in the treatment of patients with symptomatic gastritis.

Adult↗

Buccal mucosa immunofluorescence in coeliac disease and dermatitis herpetiformis.

The buccal mucosa in both coeliac disease and dermatitis herpetiformis behaves in the same manner as the skin with regard to immunofluorescence. The simple technique of buccal punch biopsy can be used to give further confirmation of the diagnosis of dermatitis herpetiformis and, especially in patients with an equivocal diagnosis, may prove easier than carrying out repeated skin biopsies.

Adolescent↗

Small intestinal structure and passive permeability in systemic sclerosis.

Seventeen patients with proven systemic sclerosis had a peroral jejunal biopsy performed. Four biopsies were regarded as showing abnormalities, which were mostly confined to the deeper structures, although in two there was a minimal degree of villous atrophy without epithelial cell changes. Passive intestinal permeability, as assessed by the cellobiose/mannitol test, was normal in all patients. In contrast, seven patients had a low xylose test result, which in five of them could be accounted for by impaired renal function, small intestinal bacterial contamination, or altered gastrointestinal transit. These results indicate that passive intestinal permeability is unaltered in systemic sclerosis, and that malabsorption, when it occurs, is caused by other factors.

Adolescent↗

Intestinal permeability and screening tests for coeliac disease.

In disease states of the small intestine--for example, gluten-sensitive enteropathy--there is an increased permeability to large molecules. This increased permeability extends to polar molecules of intermediate size such as disaccharides, whereas small polar molecules are malabsorbed. A recently-developed oral test, based on the simultaneous administration of two test substances, cellobiose (a disaccharide) and mannitol (a small polar molecule) has been used to investigate permeability in a variety of gastrointestinal diseases, the result of the test being expressed as the ratio (cellobiose/mannitol) of the five hour urinary recoveries of the two probe molecules. Results for patients with pancreatic insufficiency, intestinal bacterial overgrowth, primary hypolactasia, ileocolic or colonic Crohn's disease, and ulcerative colitis were comparable with those in normal controls, whereas in 23 out of 24 untreated coeliacs, and five out of eight patients with Crohn's disease involving the more proximal small bowel, the cellobiose/mannitol ratio was clearly abnormal. A study of its application as a screening procedure for coeliac disease showed that the test was both sensitive and accurate, with fewer false-positive and false-negative results than other recognised screening tests--namely, the xylose test, reticulin antibodies, and blood folate estimations.

Adult↗

Proximal stomach and antrum in stomach emptying.

In a series of measurements of liquid-phase gastric emptying using a radionuclide marker on 35 subjects, five were identified in whom the proximal stomach and antrum were clearly distinguishable. Three of these subjects were normal controls and two suffered from systemic sclerosis. In the three normal subjects, analysis of the movement of the liquid showed the expected movement from fundus to antrum and thence through the pylorus. In the two patients with systemic sclerosis, there was, in contrast, evidence of mass retropulsion of the contents of the antrum into the fundus. In such cases, the measurement of stomach emptying based on the assumption of a single-compartment system in likely to be misleading.

Gastric Emptying↗

Intestinal permeability in rats infected by Nippostrongylus brasiliensis.

Passive intestinal permeability has been investigated in rats infected by the nematode, Nippostrongylus brasiliensis, by the simultaneous administration of two probe molecules. Experiments using a closed intestinal loop show that there is a significantly increased absorption of lactulose and decreased absorption of mannitol in rats at the 10th to 11th day of infection. Experiments using serial oral administration techniques show that these changes start during the second week of the infection with a return towards normal values by the end of the third week. The results are similar to those found in human coeliac disease and add weight to previous studies which have stressed the similarity in the two disease processes.

Animals↗