Search

Background: Giardia lamblia causes infection of the small intestine, which leads to malabsorption and chronic diarrhoea., Aim: To characterise the inherent pathomechanisms of G lamblia infection., Methods: Duodenal biopsy specimens from 13 patients with chronic giardiasis and from controls were obtained endoscopically. Short-circuit current (I(SC)) and mannitol fluxes were measured in miniaturised Ussing chambers. Epithelial and subepithelial resistances were determined by impedance spectroscopy. Mucosal morphometry was performed and tight junction proteins were characterised by immunoblotting. Apoptotic ratio was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling staining., Results: In giardiasis, mucosal surface area per unit serosa area was decreased to 75% (3%) of control, as a result of which epithelial resistance should increase. Instead, epithelial resistance of giardiasis biopsy specimens was decreased (19 (2) vs 25 (2) Omega cm(2); p<0.05) whereas mannitol flux was not significantly altered (140 (27) vs 105 (16) nmol/h/cm(2)). As structural correlate, reduced claudin 1 expression and increased epithelial apoptosis were detected. Furthermore, basal I(SC) increased from 191 (20) in control to 261 (12) microA/h/cm(2) in giardiasis. The bumetanide-sensitive portion of I(SC) in giardiasis was also increased (51 (5) vs 20 (9) microA/h/cm(2) in control; p<0.05). Finally, phlorizin-sensitive Na(+)-glucose symport was reduced in patients with giardiasis (121 (9) vs 83 (14) microA/h/cm(2))., Conclusions: G lamblia infection causes epithelial barrier dysfunction owing to down regulation of the tight junction protein claudin 1 and increased epithelial apoptoses. Na(+)-dependent d-glucose absorption is impaired and active electrogenic anion secretion is activated. Thus, the mechanisms of diarrhoea in human chronic giardiasis comprise leak flux, malabsorptive and secretory components.

Background: The common but incompletely understood entity of malabsorption of food bound cobalamin is generally presumed to arise from gastritis and/or achlorhydria., Aim: To conduct a systematic comparative examination of gastric histology and function., Subjects: Nineteen volunteers, either healthy or with low cobalamin levels, were prospectively studied without prior knowledge of their absorption or gastric status., Methods: All subjects underwent prospective assessment of food cobalamin absorption by the egg yolk cobalamin absorption test, endoscopy, histological grading of biopsies from six gastric sites, measurement of gastric secretory function, assay for serum gastrin and antiparietal cell antibodies, and direct tests for Helicobacter pylori infection., Results: The six subjects with severe malabsorption (group I) had worse histological scores overall and lower acid and pepsin secretion than the eight subjects with normal absorption (group III) or the five subjects with mild malabsorption (group II). However, histological findings, and acid and pepsin secretion overlapped considerably between individual subjects in group I and group III. Two distinct subgroups of three subjects each emerged within group I. One subgroup (IA) had severe gastric atrophy and achlorhydria. The other subgroup (IB) had little atrophy and only mild hypochlorhydria; the gastric findings were indistinguishable from those in many subjects with normal absorption. Absorption improved in the two subjects in subgroup IB and in one subject in group II who received antibiotics, along with evidence of clearing of H pylori. None of the subjects in group IA responded to antibiotics., Conclusions: Food cobalamin malabsorption arises in at least two different gastric settings, one of which involves neither gastric atrophy nor achlorhydria. Malabsorption can respond to antibiotics, but only in some patients. Food cobalamin malabsorption is not always synonymous with atrophic gastritis and achlorhydria, and hypochlorhydria does not always guarantee food cobalamin malabsorption.

This study describes small bowel push enteroscopy in routine clinical practice, using a purpose designed instrument (Olympus SIF-10). Fifty six patients had a total of 60 procedures over a two and a half year period. The median (range) depth of small intestine intubated was 45 (15-90) cm. Procedure time varied from 10-45 minutes. Most enteroscopies were performed during routine gastroscopy lists. The technique was comparatively easy for experienced endoscopists to learn. Forty two procedures were for diagnostic purposes. Eleven patients had gastrointestinal bleeding where the source was obscure, or where early investigations had suggested a small bowel source: a specific diagnosis was made in 45% of these cases. Of seven iron deficient anaemic patients using non-steroidal anti-inflammatory drugs (NSAIDs), only one had a lesion detected in the upper small bowel. Nine patients had abnormal small bowel barium studies. Small bowel abnormalities were seen in six cases and were definitively diagnostic in three of these; in three patients the barium study appearances were confirmed as artefact. Fifteen patients were investigated for abdominal symptoms suggesting small bowel obstruction or malabsorption: a diagnosis was made in five cases. Fifteen patients underwent enteroscopy for therapeutic purposes, including successful treatment of difficult enteral feeding problems by nasojejunal tubes or by cutaneous endoscopic jejunostomies, polypectomy for Peutz-Jeghers syndrome, and dilatation of strictures. Additionally, bleeding lesions detected in patients during investigation of anaemia were successfully treated at the time by YAG laser or bipolar diathermy. In conclusion, push enteroscopy is a practical and valuable clinical service, which should probably become available on a subregional basis.

Cell kinetics in the proximal jejunal epithelium were studied by the methods of Cairnie et al. and Wright et al. Seventeen children with untreated malabsorption syndrome and cow's milk protein intolerance (CMI) and 12 of these on a cow's milk free diet were compared with 47 children with untreated coeliac disease, with 15 of these on a gluten free diet, and with 15 controls. The total number of cells in the crypts of the patients with CMI was 1.8 times (P less than 0.001) and in patients with coeliac disease 2.4 times (P less than 0.001) that seen in the controls. During the elimination diet the total number of cells in the crypts returned to the level seen in the controls. The mitotic indices, both crude and corrected, were significantly higher (P less than 0.001) in untreated patients with CMI and those with coeliac disease than in the controls. During dietary treatment the indices fell, but not quite to the level of the controls. These small differences between the two groups may be due to the difference in the causative agents or to the different ages of the patients.

A child is reported with unequivocal gluten and cow's milk protein-induced enteropathy. This is believed to be the first reported case of this association.

Jejunal brush border glucose transport was studied in a patient with glucose-galactose malabsorption and in controls, using jejunal brush border membrane vesicles (BBMV) prepared from conventional jejunal biopsies. Whereas BBMV from controls showed a seven-fold enhancement of D-glucose uptake in the presence of an inwardly directed sodium gradient compared with its absence, no such enhancement was seen in the patient's vesicles. In BBMV from the patient, initial D-glucose uptake under sodium gradient conditions was only 10% of the mean control value. In contrast, sodium/proton exchange in BBMV from the patient was intact. These data provide the first unequivocal evidence that the jejunal brush border membrane is the site of a specific defect in sodium dependent glucose transport in glucose-galactose malabsorption. Measurement of glucose uptake by BBMV may well be the optimal diagnostic technique in this disorder.

Intestinal biopsies from 146 patients with adult coeliac disease and 13 patients with intestinal villous atrophy of different aetiology were assessed for the presence of subepithelial collagen and compared with a group of 20 control subjects. Subepithelial collagen was a common and non-specific finding observed in intestinal biopsies from patients suffering from adult coeliac disease (36%) and tropical sprue. In adult coeliac disease the described subepithelial changes usually regress following treatment, though marked subepithelial collagen deposition may indicate a poor prognosis. The study showed that the presence of marked subepithelial collagen in a flat jejunal biopsy does not define a separate clinical entity.

The mean small intestinal intraepithelial lymphocyte count in seven children with untreated cow's milk protein intolerance (CMPI) on a milk-containing diet was significantly higher than 22 control children also having a milk-containing diet. Ten milk-intolerant children on a milk-free diet had a mean intraepithelial lymphocyte count which was significantly lower than the level in the 22 control children on a milk-containing diet. When these 10 children were challenged with cow's milk they relapsed clinically, and in every case the intraepithelial lymphocyte count rose, although it remained within normal limits. Nineteen children on milk-free diets who had recovered from CMPI had a mean lymphocyte count which was also significantly lower than controls on normal diets, suggesting that when milk is remo-ed from the diet the lymphocyte count is low regardless of whether the child is milk sensitive or not. The reaction of intraepithelial lymphocytes to milk in CMPI is markedly different from their response to gluten in coeliac disease.

Four consecutive patients with systemic mastocytosis were studied. One patient had a malabsorption syndrome with only minor histological changes of the intestinal mucosa. Another patient with ulcer diathesis had a gastric secretory pattern resembling Zollinger-Ellison syndrome. Serum gastrin and histamine levels were consistently normal in all patients. Endoscopy of stomach and colon disclosed urticaria-like papulae either spontaneously or after topical provocation in all patients. No increase of mast cells was found in multiple mucosal biopsies. A markedly increased gastric tissue content of histamine was found, however, in the three patients studied. The findings suggest that urticaria-like lesions associated with a high tissue content of histamine may be more important that hyperhistaminaemia in causing the various gastrointestinal symptoms.

The activities of jejunal mucosal peptide hydrolases for glycylglycine, glycyl-L-leucine and L-leucylglycine, were assayed in 37 patients. Eight patients, four of whom had Crohn's disease, were found to have a marked reduction in the activity of glycylglycine dipeptidase and, to a lesser extent, of the other two hydrolases. Although absorption of glycine in the two groups was similar, there was malabsorption of glycylglycine in the patients with reduced dipeptidases as shown by a flat absorption curve. The importance of peptide hydrolases of small-intestinal mucosa in the final digestion of proteins, and the implications of peptidase deficiency in disease states is discussed. It is concluded that significant peptidase deficiency may occur even when the mucosa is otherwise histologically completely normal, similar to some states of disaccharidase deficiency described in recent years.