Jüri Johannes Rumessen

Functional Bowel Disease: Malabsorption and Abdominal Distress After Ingestion of Fructose, Sorbitol, and Fructose-Sorbitol Mixtures

Twenty-five patients with functional bowel disease were given fructose, sorbitol, fructose-sorbitol mixtures, and sucrose. The occurrence of malabsorption was evaluated by means of hydrogen breath tests and the gastrointestinal symptoms, if any, were recorded. One patient could not be evaluated because of lack of H2 production. Based on a cut-off level of 10 ppm rise of H2 concentration, malabsorption was apparent in 13 patients, in 7 of which the calculated absorption capacities were below 15 g. In contrast, in patients given 50 g of sucrose, malabsorption could not be detected. Ingestion of fructose caused marked abdominal distress in patients with demonstrable malabsorption. Ingestion of sucrose in these patients gave less pronounced symptoms of abdominal distress. Malabsorption of a 5-g dose of sorbitol could be detected in 8 of 13 patients. Mixtures of 25 g of fructose and 5 g of sorbitol caused significantly increased abdominal distress, and more than additive malabsorption was found in several cases. The present study shows that pronounced gastrointestinal distress may be provoked by malabsorption of small amounts of fructose, sorbitol, and fructose-sorbitol mixtures in patients with functional bowel disease. The findings may have direct influence on the dietary guidance given to a major group of patients with functional bowel disease and may make it possible to define separate entities in this disease complex.

Ultrastructure of interstitial cells of Cajal associated with deep muscular plexus of human small intestine

Evidence showing that interstitial cells of Cajal have important regulatory functions in the gut musculature is accumulating. In the current study, the ultrastructure of the deep muscular plexus and associated interstial cells of Cajal in human small intestine were studied to provide a reference for identification and further physiological or pathological studies. The deep muscular plexus was sandwiched between a thin inner layer of smooth muscle (one to five cells thick) and the bulk of the circular muscle. Interstitial cells of Cajal in this region very much resembled smooth muscle cells (with a continuous basal lamina, caveolae, intermediate filaments, dense bodies, dense bands, and a well-developed subsurface smooth endoplasmic reticulum), but the arrangement of organelles was clearly different, and cisternae of granular endoplasmic reticulum were abundant. Interstitial cells of Cajal were distinguished from fibroblasts or macrophages in the region. They ramified in the inner zone of the outer division of circular muscle, penetrated the inner-most circular layer, and were also found at the submucosal border. They were in close, synapselike contact with nerve terminals of the deep muscular plexus, and only few gap junctions with other interstitial cells of Cajal or with the musculature were observed. Compared with interstitial cells of Cajal from other mammals, those associated with the deep muscular plexus in the human small intestine more closely resemble smooth muscle cells, and their organization appears more diffuse; however, the ultrastructure and organization of interstitial cells of Cajal is compatible with modulatory actions on the circular muscle also in humans.

Fructose and Related Food Carbohydrates: Sources, Intake, Absorption, and Clinical Implications

It is possible to point out subjects consuming considerable quantities of fructose and sorbitol, and the intake seems to be increasing both from added and natural sources. Studies of the absorption of fructose in animals are inconsistent, and the mechanisms of fructose uptake seem to vary in accordance with the species. In most species fructose absorption takes place by a specific carrier (facilitated transport), but it may be active in the rat. In vitro studies of human intestine are very scarce; there is no evidence of active intestinal fructose transport in the human intestine. By means of hydrogen breath tests, a very low absorption capacity for fructose given as the free monosaccharide has been found in humans. Fructose given as sucrose or in equimolar combinations with glucose is well absorbed, and only fructose in excess of glucose is malabsorbed. On this basis it is hypothesized that two different uptake mechanisms for fructose are present in the human intestine. One of these may be a disaccharidase-related uptake system. Sorbitol ingestion may aggravate malabsorption of fructose given as the monosaccharide; it is not known whether a specific mechanism is involved. In children and adults with functional bowel distress the absorption capacities for fructose may not differ from those of healthy individuals, but malabsorption of fructose and/or sorbitol may be the cause of or aggravate abdominal symptoms. Fructose polymers (fructans) are also subject to increasing nutritional interest. Fructans are not absorbed in the small intestine but are strongly fermented in the large bowel. Fructans may be of potential benefit for large-bowel function and blood glucose regulation.

Interstitial cells of Cajal in human small intestine. Ultrastructural identification and organization between the main smooth muscle layers.

Previous morphological and electrophysiological studies have supported the hypothesis that interstitial cells of Cajal have important regulatory (pacemaker) functions in the gut. In the current study, interstitial cells of Cajal associated with Auerbachs plexus in human small intestine were studied. Freshly resected intestine was examined by light and electron microscopy. The interstitial cells of Cajal resembled modified smooth muscle cells. They had caveolae and dense bodies, an incomplete basal lamina, a very well-developed smooth endoplasmic reticulum, and abundant intermediate (10 nm) filaments. Myosin filaments were not seen. Fibroblast-like cells were distinguished by their lack of caveolae and dense bodies, the relative scarcity of smooth cisternae and intermediate filaments, and the abundant granular endoplasmic reticulum. Interstitial cells of Cajal were arranged in networks of bundles containing processes of two to seven cells with fibroblastlike cells interspersed in the bundles. The bundles were innervated by nerve elements of Auerbachs plexus and extended into both layers of smooth muscle, between muscle cells, and into septa. The bundles were closely associated with elastin fibers. The organization shown in this study strongly supports the concept of interstitial cells of Cajal as important regulatory cells also in the human small intestine. The characteristic cytology and organization of interstitial cells of Cajal may provide a basis for future morphological, electrophysiological, and pathological studies of these cells in human small intestine.

Pacemaker cells in the gastrointestinal tract: interstitial cells of Cajal.

Interstitial cells of Cajal (ICC) were described a century ago as primitive neurons in the intestines. Through the years, ICC have been mistaken for neurons, glial cells, fibroblasts, smooth muscle cells, and macrophages. We identified ICC in the musculature of mouse small intestine by their characteristic morphology and topography, and we analysed the relation between ICC, autonomic nerves, and smooth muscle. Subsequent morphological and electrophysiological evidence has strongly supported our hypotheses that some ICC populations are gut pacemakers and may hold other fundamental regulatory functions (coordinative, mechanoreceptive, mediating nervous input). Recognition of common principles of ICC organization (confinement to specific locations in relation to smooth muscle layers; formation of extensive cellular networks through tight coupling of overlapping thin processes; innervation patterns; characteristic patterns of contact with smooth muscle cells) and ultrastructure (myoid features: basal lamina, caveolae, rich in sER and mitochondria, often prominent filament bundles and dense bands/bodies) has allowed the identification of ICC in the GI musculature of all species investigated. However, variation in organization and ultrastructure is significant, between both species and regions of the GI tract. Our studies of ICC in human intestine permit an extension of the above hypotheses to man and provide a basis for further studies of ICC pathology and pathophysiology. The latter may become a fruitful area of research in the coming decades.

Ultrastructure of interstitial cells of Cajal in circular muscle of human small intestine

BACKGROUND Interstitial cells of Cajal (ICC) may be important regulatory cells in gut muscle layers. This study examined ICC within the circular muscle of human small intestine. METHODS Surgically resected, uninvolved intestine was studied by light microscopy and electron microscopy. RESULTS Muscle lamellae were separated by main septa in continuity with submucosa. Smooth muscle cells ran radially in the septa. Two types of ICC were distinguished. One ICC type had abundant intermediate filaments and smooth cisternae and a discontinuous basal lamina. This ICC type was present in the septa and in the outer third of the circular lamellae. The other ICC type had a complete basal lamina and conspicuous caveolae. This ICC type was observed only in the inner third of the circular lamellae. Both ICC types were close to nerves, but only the latter type formed gap junctions with one another and with muscle cells. Junctions between the two ICC types were not observed. CONCLUSIONS The arrangement suggests that ICC and radially oriented muscle cells participate in electrical and mechanical coordination of the circular muscle layer of human small intestine.

A randomised double-blind placebo-controlled trial with Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis BB-12 for maintenance of remission in ulcerative colitis

BACKGROUND AND AIMS To investigate the clinical effect of treatment with Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis BB-12 (Probio-Tec AB-25) to maintain remission in patients with ulcerative colitis. METHODS Patients with left-sided ulcerative colitis in remission - including proctitis and at least one relapse within the last year were randomised (2:1) in a double-blind placebo-controlled study to Probio-Tec AB-25 or placebo for 52 weeks. The patients were evaluated clinically, endoscopically and histologically at entry and if relapsing. No other medication for ulcerative colitis than the study drug was allowed during the study. Primary endpoint was maintenance of clinical remission, secondary endpoints comparisons of days to relapse, and safety and tolerability of the study drug. The concentrations of the probiotic bacterial strains in stool were analysed in a subset of patients. RESULTS Thirty-two patients were randomised. Twenty patients received Probio-Tec AB-25 and twelve patients received placebo. Five patients (25%) in the Probio-Tec AB-25 group and one patient (8%) in the placebo group maintained remission after 1 year of treatment (p=0.37). The median time to relapse was 125.5days (range 11-391 days) in the probiotic group and 104 days (range 28-369 days) in the placebo group respectively, (p=0.683). Probio-Tec AB-25 was overall well tolerated. CONCLUSIONS In this small randomised placebo-controlled trial no significant clinical benefit of Probio-Tec AB-25 could be demonstrated in comparison with placebo for maintaining remission in patients with left-sided ulcerative colitis. A difference may be achieved in larger studies, but the clinical significance of this would be questionable. This study was registered in ClinicalTrial.gov (NCT00268164).

Bile Acid Malabsorption in Patients with Chronic Diarrhoea: Clinical Value of SeHCAT Test

Background: Bile acid malabsorption (BAM), a cause of chronic diarrhoea, can be diagnosed by the SeHCAT test. The purpose of this study was to evaluate the usefulness of SeHCAT testing by assessing the extent of BAM and describing the clinical characteristics in a group of patients with chronic diarrhoea. Clinical outcome after treatment with cholestyramine was also evaluated. Methods: During a 5-year period (1997-2001) the SeHCAT test was performed in 135 patients in whom a primary programme for diagnostic evaluation of chronic diarrhoea had not revealed a cause. File data from 133 patients could be evaluated. Results: In 44% of patients, bile acid absorption was normal with SeHCAT retention S 15%. Impaired SeHCAT retention was found in 56%. All patients with ileocaecal resections had retention values <10%. Patients with microscopic colitis presented with BAM in 39%. Only one patient with idiopathic BAM presented with steatorrhoea as opposed to 11 patients with type 1 and 3 BAM. Patients with idiopathic BAM and/or SeHCAT retention values <5% had the best response to treatment with cholestyramine. Conclusions: The SeHCAT test is of value in evaluation of patients with chronic diarrhoea as a second-line investigation with a high diagnostic yield. The only a priori parameter to predict BAM was the existence of ileocaecal resections. The result of the SeHCAT test seems to predict the benefit of treatment with cholestyramine.BACKGROUND Bile acid malabsorption (BAM), a cause of chronic diarrhoea, can be diagnosed by the SeHCAT test. The purpose of this study was to evaluate the usefulness of SeHCAT testing by assessing the extent of BAM and describing the clinical characteristics in a group of patients with chronic diarrhoea. Clinical outcome after treatment with cholestyramine was also evaluated. METHODS During a 5-year period (1997-2001) the SeHCAT test was performed in 135 patients in whom a primary programme for diagnostic evaluation of chronic diarrhoea had not revealed a cause. File data from 133 patients could be evaluated. RESULTS In 44% of patients, bile acid absorption was normal with SeHCAT retention > or = 15%. Impaired SeHCAT retention was found in 56%. All patients with ileocaecal resections had retention values < 10%. Patients with microscopic colitis presented with BAM in 39%. Only one patient with idiopathic BAM presented with steatorrhoea as opposed to 11 patients with type 1 and 3 BAM. Patients with idiopathic BAM and/or SeHCAT retention values < 5% had the best response to treatment with cholestyramine. CONCLUSIONS The SeHCAT test is of value in evaluation of patients with chronic diarrhoea as a second-line investigation with a high diagnostic yield. The only a priori parameter to predict BAM was the existence of ileocaecal resections. The result of the SeHCAT test seems to predict the benefit of treatment with cholestyramine.

Metabolic and inflammatory faecal markers in collagenous colitis.

Objectives To evaluate the excretion of the inflammatory and metabolic faecal markers calprotectin, lactoferrin, and short-chain fatty acids in symptomatic and quiescent collagenous colitis. Methods Faecal samples from 21 patients with active collagenous colitis, 12 patients retested in remission, and 13 controls were analysed. Calprotectin was determined using an enzyme-linked immunosorbent assay. Lactoferrin was estimated by a latex agglutination test. Short-chain fatty acids were determined by steam distillation followed by gas–liquid chromatography. Results Calprotectin was increased in patients with active collagenous colitis [80 μg/g (6.25–1899)] (median and range) compared with patients with quiescent collagenous colitis [26 μg/g (6.25–340)], P=0.025 and controls [6.25 μg/g (6.25–99)], P=0.002. Eight patients (38%) with active collagenous colitis had normal levels of calprotectin. Lactoferrin was detected in one patient only. Concentrations of total short-chain fatty acids did not differ in patients with active collagenous colitis compared with quiescent collagenous colitis or controls (P=0.75), whereas concentrations of the branched-chain fatty acids were decreased in patients with active collagenous colitis versus controls (P<0.005). In-vitro incubations demonstrated increased ratios of acetate in patients with active and quiescent collagenous colitis compared with controls (P<0.05), with a corresponding decrease in branched-chain fatty acids ratios (P<0.05). Conclusion Faecal calprotectin was increased in collagenous colitis; however, increased excretion was not a universal finding limiting the use of calprotectin as an inflammatory marker in collagenous colitis. Faecal lactoferrin was almost undetectable. Luminal fermentative conditions are altered in collagenous colitis. Fermentative alterations could be secondary to changes in substrate availability and intestinal transit time.

Characterization of macrophage-like cells in the external layers of human small and large intestine

SummaryIn the external layers of human small and large intestine macrophage-like cells were characterized by immunohistochemical, histochemical and electronmicroscopical methods. Using immunohistochemistry and a number of monoclonal antibodies, the presence and distribution of phenotypic subpopulations of macrophages were evaluated. In all locations macrophage-like cells were identified with antibody EBM11, which recognizes CD68 antigen, C3bi which recognizes CD11b, and partly with an antibody which recognizes protein 150,95 (CD11c). Macrophage-like cells in the external muscle layer were HLA-DR-positive (expressing the MHC class-II antigen), in contrast to macrophage-like cells in the subserosa and submucosa. Macrophage-like cells in the external muscle layer were mostly acid phosphatase-negative, and at the electron-microscopic level they were found to have features of macrophages: primary lysosomes, coated vesicles and pits. However, very few secondary lysosomes were present. Birbeck granules were not observed. It is concluded that in the external muscle layer of human small and large intestine numerous macrophages of a special type are present. It is discussed whether this cell type plays a role in gastrointestinal motility and/or has an immunological function.