Role of bile acids and bile acid binding agents in patients with collagenous colitis.

BACKGROUND: In a retrospective study bile acid malabsorption was observed in patients with collagenous colitis. AIMS: To study the occurrence of bile acid malabsorption and the effect of bile acid binders prospectively in patients with chronic diarrhoea and collagenous colitis. METHODS: Over 36 months all patients referred because of chronic diarrhoea completed a diagnostic programme, including gastroscopy with duodenal biopsy, colonoscopy with biopsies, and the (75)Se-homocholic acid taurine ((75)SeHCAT) test for bile acid malabsorption. Treatment with a bile acid binder (cholestyramine in 24, colestipol in three) was given, irrespective of the results of the (75)SeHCAT test. RESULTS: Collagenous colitis was found in 28 patients (six men, 22 women), 27 of whom had persistent symptoms and completed the programme. Four patients had had a previous cholecystectomy or a distal gastric resection. The (75)SeHCAT test was abnormal in 12/27 (44%) of the collagenous colitis patients with (75)SeHCAT values 0.5-9.7%, and normal in 15 patients (56%). Bile acid binding treatment was followed by a rapid, marked, or complete improvement in 21/27 (78%) of the collagenous colitis patients. Rapid improvement occurred in 11/12 (92%) of the patients with bile acid malabsorption compared with 10/15 (67%) of the patients with normal (75)SeHCAT tests. CONCLUSION: Bile acid malabsorption is common in patients with collagenous colitis and is probably an important pathophysiological factor. Because of a high response rate without serious side effects, bile acid binding treatment should be considered for collagenous colitis, particularly patients with bile acid malabsorption.

Oral budesonide versus prednisolone in patients with active extensive and left-sided ulcerative colitis.

BACKGROUND & AIMS: Systemic glucocorticosteroids (GCSs) have proven efficacy in active ulcerative colitis but cause undesired systemic side effects. Therefore, new GCSs with high topical activity and a high rate of metabolism may be of clinical value in this condition. The aim of this study was to explore the efficacy and safety of the topically acting GCS budesonide in an oral controlled-release formulation in extensive or left-sided, mild to moderately active ulcerative colitis. METHODS: A 9-week, randomized, double-blind, controlled trial was performed, and treatments with 10 mg budesonide or 40 mg prednisolone daily, both gradually tapered, were compared. Endoscopic improvement and effect on endogenous plasma cortisol were assessed. RESULTS: Thirty-four patients were administered budesonide, and 38 patients were administered prednisolone. Mean endoscopic scores improved significantly in both groups but without difference between the groups. Five patients in the budesonide group and 7 patients in the prednisolone group deteriorated and were withdrawn from the study. Morning plasma cortisol levels were suppressed in the prednisolone group (entry, 449 nmol/L; 2 weeks, 116 nmol/L; 4 weeks, 195 nmol/L) but were unchanged in the budesonide group. CONCLUSIONS: The GCS budesonide administered in an oral controlled-release formulation seems to give an overall treatment result in active ulcerative colitis approaching that of prednisolone but without suppression of plasma cortisol levels. This concept merits further evaluation.

Serum antibodies to gliadin in coeliac disease after gluten withdrawal.

Serum gliadin antibodies of the IgA and IgG classes were determined by the diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA) in 10 adult patients with villous atrophy of the small-intestinal mucosa. After introduction of a gluten-free diet a gradual decrease in serum gliadin antibody levels occurred, reaching statistical significance at 3 months of treatment for the IgA class (p less than 0.01) and at 6 months for the IgG class (p less than 0.05). A decrease of serum gliadin antibody levels after gluten withdrawal was related to an improvement of the intestinal mucosa and should thus be indicative of whether the patient is following the dietary recommendations. However, determination of gliadin antibody levels cannot replace small-intestinal biopsy, as there are a few patients in whom the antibody levels are not related to the morphology of the gut mucosa.

Intestinal fluid and electrolyte transport in man during reduced circulating blood volume.

The effect on intestinal net transport of fluid and electrolytes of a reduced circulating blood volume was studied in the human jejunum with the triple lumen perfusion technique. The blood volume was reduced by changing the lower extremities from an elevated to a dependent position combined with a venous stasis. The tilting manoeuvre, probably resembling a bleeding of about 600-800 ml, significantly increased net absorption of fluid, sodium and chloride while glucose transport was unaffected. Concomitantly the blood flow decreased and vascular resistance increased in the forearm vascular bed. The results are consistent with the hypothesis that activity in the sympathetic nervous system initiated from unloading of the cardiopulmonary volume receptors enhances intestinal absorption of fluid and electrolytes. The results also indicate that the human intestines are an important target organ in the compensatory mechanisms activated during hypovolaemia due to - for example, haemorrhage.

Spontaneous remission of dermatitis herpetiformis: dietary and gastrointestinal studies.

Out of 98 patients with dermatitis herpetiformis (DH) living in Gothenburg, 14 were in spontaneous remission (29% of the patients without gluten free diet). Eight of these volunteered for dietary interviews and further studies. They do not seem to differ from symptomatic DH patients in the frequency of HLA-B8, achlorhydria or small-bowel enteropathy. Their estimated mean daily intake of gluten was below 12 g in six. The mean gluten intake of the eight patients in remission is significantly less than in a group of 34 patients with dapsone-requiring DH on non-restricted diet. Urinary iodine excretion was low in five, all previously instructed to restrict their iodine intake. Dietary factors could thus be suspected to be responsible for some spontaneous remissions in DH.

Serum antibodies to gliadin and small-intestinal morphology in dermatitis herpetiformis. A controlled clinical study of the effect of treatment with a gluten-free diet.

Serum gliadin antibodies of the IgA and IgG classes were determined by the diffusion-in-gel enzyme-linked immunosorbent assay in 41 patients with dermatitis herpetiformis before treatment with a gluten-free diet. Increased gliadin antibody levels were found more frequently in patients with subtotal villous atrophy (9 out of 17 patients, or 53%; p less than 0.05) than in patients with partial villous atrophy (2 out of 13 patients, or 15%) or normal villous appearance (2 out of 10 patients, or 20%). The gliadin antibody levels were negatively correlated with the urinary xylose excretion (r = -0.40, p less than 0.02 for the IgA class and r = -0.64, p less than 0.001 for the IgG class). Intestinal morphology improved and mean gliadin antibody levels of the IgA and IgG classes decreased during treatment with a gluten-free diet for 16-36 months (mean, 20 months) (p less than 0.005, n = 26), whereas no significant changes of the gliadin antibody levels or the small-intestinal morphology were observed in the other 15 patients, who continued on a non-restricted diet for 17-35 months (mean, 20 months). Thus, gliadin antibody levels in sera from patients with dermatitis herpetiformis seem to be correlated with the severity of the intestinal disease. However, all patients with villous atrophy are not detected by determination of serum gliadin antibodies.

Hydrogen (H2) breath test and gastric bacteria in acid-secreting subjects and in achlorhydric and postgastrectomy patients before and after antimicrobial treatment.

Sixteen patients with pentagastrin-fast achlorhydria and 12 patients who had undergone Billroth II gastrectomy (at least 3 years previously) were compared with 10 acid-secreting volunteers and 13 patients with endoscopically proven peptic disease. The concentration and type of gastric bacteria were analysed in achlorhydrics, Billroth II patients, and patients with peptic disease. A 6-h hydrogen (H2) breath test after a standardized meal was performed in all subjects. The mean concentration of gastric bacteria was significantly higher in achlorhydrics and Billroth II patients than in patients with peptic disease. End-expiratory H2 excretion was elevated in achlorhydrics and Billroth II patients to levels significantly exceeding those of acid-secreting volunteers and patients with peptic disease. In achlorhydrics, total bacterial concentration in gastric juice was correlated to H2 excretion between 60 and 180 min after the meal. Treatment of achlorhydric and postgastrectomy patients with trimethoprim/sulphamethoxazole lowered H2 breath concentrations in both groups and reduced symptoms in achlorhydrics. Elevated end-expiratory H2 levels after a test meal indicate upper gastrointestinal bacterial overgrowth in achlorhydrics and in postgastrectomy patients.

The rate of healing of duodenal ulcers during omeprazole treatment.

We have studied the rate of healing of duodenal ulcers in 44 patients treated with omeprazole, 40 mg once daily for 4 weeks, with or without an 80-mg loading dose on day 1. Fourteen patients (32%) had healed by the end of the 1st week's treatment and a further 27 after a further week (giving a cumulative total of 93%). All patients (100%) had healed by the end of the treatment period. There was no significant difference in healing rate between the two treatment groups. Ulcer symptoms were relieved rapidly, and the drug was well tolerated.

Upper gastrointestinal and mental symptoms in the irritable bowel syndrome.

Gastrointestinal and mental symptoms were assessed in 101 outpatients with the irritable bowel syndrome (IBS). A normal female population was used for comparison of mental symptoms. By definition all patients had abdominal pains and/or change of bowel habits (constipation or diarrhoea, or both) but no demonstrable organic disease. Upper gastrointestinal symptoms without peptic ulcer disease were reported by 87% of the patients. Mental symptoms were reported by almost all patients. Symptoms of anxiety, fatiguability, hostile feelings, sadness, and sleep disturbances were seen significantly more often among IBS women than in the controls. We conclude that patients with IBS frequently have upper gastrointestinal and mental symptoms that should be taken into account in the therapeutic management and evaluation of new modes of treatment.

Symptom profiles in chronic peptic ulcer disease. A detailed study of abdominal and mental symptoms.

Abdominal and mental symptoms were assessed in 103 outpatients with chronic peptic ulcer disease. Patients with present symptoms and a history of duodenal or prepyloric ulcer were included if they had no other disorder requiring treatment. A normal female population was used for comparison of mental symptoms. Besides the cardinal ulcer or acid-related symptoms, there was a high rate of indigestion and bowel dysfunction symptoms, usually associated with the irritable bowel syndrome. Mental symptoms were reported by almost all patients. Symptoms of anxiety, depression, and neurasthenia were seen significantly more often among the female patients than in the normal women. We conclude that a wide range of both abdominal and mental symptoms should be taken into account in the therapeutic management of peptic ulcer disease, in evaluation of clinical trials, and in studies of the natural history.

Gastric morphology and function in dermatitis herpetiformis and in coeliac disease.

Gastric acid secretory capacity was evaluated in 116 patients with dermatitis herpetiformis by means of the pentagastrin test. Endoscopic gastric mucosal biopsy specimens were obtained from both the body and the antrum in 90 of them. Forty-eight patients (41%) had a maximal acid output less than 10 mmol/h, and 30 of them (26%) were achlorhydric. The frequency of achlorhydria increased with age, and 27 out of 58 patients (47%) more than 50 years old were achlorhydric. Antrum-sparing chronic atrophic gastritis was present in 92% of the achlorhydric patients, and hypergastrinaemia and serum parietal cell antibodies were found in most of them. The prevalence of chronic gastritis of the body and of the antrum increased with age. There was no correlation between atrophic gastritis or achlorhydria and small-intestinal villous atrophy, the results of the D-xylose test, and blood folate and serum zinc determinations. The transferrin saturation index was lower in patients with achlorhydria. The frequency of achlorhydria was significantly higher in patients with dermatitis herpetiformis than in 69 patients with coeliac disease.

Influence of gluten-free diet on the gastric condition in dermatitis herpetiformis.

Achlorhydric atrophic gastritis occurs in approximately 25% of patients with dermatitis herpetiformis (DH). The effect of gluten withdrawal on the gastric condition was studied in 35 patients, with a control group of 20 patients continuing their habitual diet. Gastrointestinal examinations were performed initially and repeated after about 1 3/4 years. Adherence to the diet was confirmed by dietary interviews, improvement of malabsorption test results and intestinal villous structure, and decreased dapsone requirement. Neither the non-restricted diet nor the gluten-free diet had any effect on gastric morphology, the ability to secrete gastric acid, serum gastrin levels, or the frequency or titres of circulating parietal cell antibodies. The findings indicate that gluten is not responsible for the perpetuation of the gastric affection in DH, in contrast to the enteropathy.

Influence of the amount of dietary gluten on gastrointestinal morphology and function in dermatitis herpetiformis.

The individual daily intake of gluten was calculated in 45 patients with dermatitis herpetiformis (DH) on the basis of a depth interview about food habits. Gastric and small intestinal morphology and function were studied concurrently. Mean daily gluten intake was estimated to be 15 g, a figure which corresponds well to the average gluten intake in Sweden. There was a significant correlation between the degree of morphological mucosal changes of the small intestine and the quantity of gluten ingested. All patients with jejunal villous atrophy consumed more than 10 g gluten daily and all but one patient with normal jejunal villous structure had a gluten intake of less than 10 g/d. The findings suggest a dose-dependent effect of gluten on the intestinal mucosa. Conversely, the daily gluten intake was not correlated to gastric morphology, gastric acid secretion, serum gastrin levels or serum parietal cell antibodies. Patients with reduced ability to secrete gastric acid did not differ from the remaining patients in this respect. Whereas the coeliac-like enteropathy in DH seems to be caused by ingested gluten, the frequently occurring achlorhydric atrophic gastritis must be assumed to be of different immunopathogenesis.

Conventional malabsorption tests: do they detect the adult patient with villous atrophy?

A total number of 134 patients with subtotal or partial villous atrophy, of whom 49 had dermatitis herpetiformis, were investigated with blood folate assay and xylose and lactose absorption tests. Faecal fat excretion was determined in 71 patients without dermatitis herpetiformis (coeliac group). A comparison was made between three patient groups, the patients with dermatitis herpetiformis and the coeliac patients studied in 1970-74 and 1975-79, respectively. From clinical and biochemical analyses of these patients we conclude that although a combination of the four malabsorption tests used here still detect a majority of coeliac patients, small intestinal biopsy may reveal villous atrophy also in patients without any laboratory evidence for malabsorption by these commonly used tests. In dermatitis herpetiformis, however, the sensitivity of the tests used was low; these malabsorption tests therefore have little diagnostic value in this category of patients.

Secretin release in coeliac disease. Plasma secretin concentration and bicarbonate output to the duodenum after intraduodenal acid infusion in coeliac patients before and after treatment.

Infusion of 40 ml 0.1 mol/l HCl into the duodenum in eight untreated coeliac patients was followed by an increase of the plasma immunoreactive secretin (IRS) concentration from 1.6 +/- 0.2 pmol/l to a peak level of 2.4 +/- 0.3 pmol/l (p less than 0.05). After treatment with a gluten-free diet, the same patients showed an increase from 1.4 +/- 0.3 pmol/l to a peak level of 5.5 +/- 0.9 pmol/l after intraduodenal acid infusion, which was significantly higher than before treatment (p less than 0.01). In control subjects, intraduodenal acid infusion was followed by an increase from 1.4 +/- 0.2 pmol/l to 6.7 +/- 1.1 pmol/l, which was significantly higher than in untreated coeliac disease (p less than 0.01) but did not differ from what was found in treated coeliac patients. Significant differences in pH, volume, or bicarbonate content of the duodenal aspirates or the basal IRS levels were not found.

Evaluation of gliadin antibodies for detection of coeliac disease.

To evaluate assay of gliadin antibodies of different immunoglobulin classes as a test for detection of coeliac disease, we analysed sera from 36 adult patients and 8 children with coeliac disease, 62 patients with other gastrointestinal diseases, and 124 blood donors with diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA). Depending on the choice of reference levels for gliadin antibodies of the IgA and IgG classes, respectively, we found a diagnostic sensitivity for coeliac disease of 93-86% and a diagnostic specificity of 95-100%. Determination of gliadin antibodies by DIG-ELISA can thus be used as a test for detection of coeliac disease and selection of patients for small-intestinal biopsy.

Quantitation of immunoglobulin-producing cells in small intestinal mucosa of patients with IgA nephropathy.

The numbers and proportions of immunocytes producing IgA, IgM, or IgG were found to be normal in the proximal small intestinal mucosa of patients with IgA nephropathy. There was no indication of any quantitative aberration in the mucosal humoral immune system at this secretory tissue site.

Chronic inflammatory bowel disease in patients with coeliac disease.

Six patients with coeliac disease and inflammatory bowel disease are described. Of special interest were two patients with coeliac disease and dermatitis herpetiformis and ulcerative colitis, one of whom also had sclerosing cholangitis. Three patients had both coeliac disease and ulcerative colitis, and one of them also had sclerosing cholangitis. In one patient with coeliac disease Crohn's disease of the small bowel was diagnosed. There seems to be association between coeliac disease without dermatitis herpetiformis, and ulcerative colitis. The possible combination of coeliac disease and inflammatory bowel disease deserves more attention than it has hitherto received.