Aetiology of acute gastroenteritis in adults requiring hospitalization in The Netherlands.

SUMMARY Infectious gastroenteritis causes a considerable burden of disease worldwide. Effective control should be targeted at diseases with the highest burden and costs. Therefore, an accurate understanding of the relative importance of the different microorganisms is needed. The objective of this study was to determine the incidence and aetiology of gastroenteritis in adults requiring hospital admission in The Netherlands. Five hospitals enrolled patients admitted with gastroenteritis for about 1 year during the period May 2008 to November 2009. Participants completed questionnaires and provided a faecal sample. The hospital completed a clinical questionnaire. In total, 44 adults hospitalized for gastroenteritis were included in the study. The cases had serious symptoms, with 31% subsequently developing kidney failure. One or more pathogens were found in 59% of cases. Overall, rotavirus (22%) was the most common infection. Co-infections were observed relatively often (22%). This study emphasizes that rotavirus can also cause serious illness in adults.

Sensitivity of a hyperosmolar or "low"-osmolar test solution for sugar absorption in recognizing small intestinal mucosal damage in coeliac disease.

Reliability of differential sugar absorption tests is hampered by a lack of standardization of the content and osmolarity of the test solutions. We evaluated the effect of osmolarity of the test solution of the sugar absorption test on the 5 hour urine excretion of orally administered lactulose and mannitol. A group of 28 controls and 14 coeliacs, with villous atrophy grade II to IV, ingested a hyperosmolar sugar absorption test solution and a "low"-osmolar solution, respectively. After an overnight fast, each subject ingested hyperosmolar sugar absorption test solution (2 g mannitol, 5 g lactulose and 40 g sucrose/100 ml (around 1,560 mmol/l)). After two days, this procedure was repeated with low-osmolar solution (2 g mannitol and 5 g lactulose/100 ml (around 375 mmol/l). The influence of the sequence of the tests on the results had previously been excluded. All urine from the 5 h-period following ingestion of the test solution was collected. To calculate the low-osmolar solution ratio, samples were analysed for lactulose and mannitol concentrations by gas chromatography The sensitivity of hyperosmolar SAT solution and low-osmolar solution for the detection of mucosal abnormalities in coeliacs was 64% and 43%, respectively. In conclusion, a hyperosmolar solution discriminates better between normal and damaged mucosa of the small bowel such as villous atrophy due to a relative increase in permeability for lactulose.

Cyclosporin in the treatment of adults with refractory coeliac disease--an open pilot study.

AIM: To evaluate the effect of cyclosporin treatment on clinical and histological parameters in adult patients with refractory coeliac disease. METHODS: Thirteen patients were treated with oral cyclosporin for 2 months, aiming at serum levels of 100-200 ng/mL. Seven extended medication intake up to a maximum of 12 months. Before and after treatment, clinical parameters were monitored and small intestinal biopsies taken. Ten of 13 patients were typed for HLA-DQA1 and -DQB1 alleles. RESULTS: Eight of 13 patients responded histologically to cyclosporin treatment. Normalization of villi was demonstrated in five patients, three after prolonged treatment. Eight patients reported a clinical response, of whom six had concomitant histological improvement. No serious side-effects of cyclosporin were noticed. Nine of 10 patients who were immunogenetically typed carried the coeliac disease associated serologic DQ2 markers, one carried neither DQ2 nor DQ8 markers. CONCLUSION: In our study group of 13 adult refractory coeliac disease patients, cyclosporin in therapeutic doses induced a histological improvement in eight patients (61%), in five of whom (38%) normalization of villi was demonstrated. Thus, we believe that cyclosporin is a therapeutic option in refractory coeliac disease, although we could not confirm earlier reports of unconditional successful treatment.

Clinical implications of the sugar absorption test: intestinal permeability test to assess mucosal barrier function.

BACKGROUND: Functional integrity as an aspect of the mucosal barrier function of the small bowel can be estimated by the intestinal permeability for macromolecules. In the first part of this paper, an overview of intestinal permeability and its measurement is given. METHODS: In the second part of the paper our own experience with the Sugar Absorption Test using lactulose and mannitol to assess mucosal barrier function of gastric, small and large bowel, respectively, is described. RESULTS AND CONCLUSIONS: The Sugar Absorption Test is not recommended as a predictor of NSAID-related upper gastrointestinal damage nor as a marker of disease activity in inflammatory bowel diseases. The Sugar Absorption Test is very useful in screening for small intestinal disease, in assessing the response to treatment, and in predicting the prognosis, especially in coeliac disease. In our opinion, the D-xylose test is obsolete.

The value of the D-xylose test compared with the differential sugar absorption test in recognizing coeliac disease.

OBJECTIVE: To compare the value of the differential sugar absorption test (SAT) with the blood and urine D-xylose tests (DXTs and DXTu) in diagnosing coeliac disease (CD) the SAT and the standard DXTs and DXTu were performed in 14 coeliacs with abnormal small bowel histology and in 12 patients with aspecific gastrointestinal complaints. METHODS: In the SAT a solution of lactulose (L) and mannitol (M) was given to the fasting patient after which the L/M ratio was measured in 5 h urine by gas chromatography. In the DXTs and DXTu a solution of 25 g D-xylose was given to the fasting patient and blood was drawn at 0, 30 and 120 min and urine was collected for 5 h, respectively. RESULTS: To measure the power in diagnosing CD of the SAT, DXTs 30 min, DXTs 120 min and DXTu, the test results were plotted in ROC curves and the areas under the curves (AUCs) were calculated. The AUCs were 0.97, 0.77, 0.78 and 0.63, respectively. CONCLUSION: In our opinion, the DXTs and DXTu are no longer useful in the investigation of mucosal function of the small bowel.

Intestinal permeability in exocrine pancreatic insufficiency due to cystic fibrosis or chronic pancreatitis.

Disturbances of the intestinal integrity, reflected by an increased intestinal permeability, are reported in cystic fibrosis (CF). Controversy exists whether the increased intestinal permeability is due to CF itself or a consequence of the concomitant exocrine pancreatic insufficiency (PI). We measured intestinal permeability by the sugar absorption test in 32 PI patients: 20 CF-PI, 12 nonCF-PI with chronic pancreatitis, and 50 controls. In the sugar absorption test, the lactulose/mannitol ratio is measured in 5-h urine samples after oral ingestion of a solution of lactulose and mannitol, hyperosmolar by the addition of sucrose. The lactulose/mannitol ratio was increased in both CF-PI and nonCF-PI versus controls (p < 0.0001). In CF, the L/M ratio and permeability for lactulose and mannitol did not change by increasing pancreatic enzyme supplementation by 30-50% for 2 wk (p = 0.74, p = 0.97, p = 0.74, respectively) nor by decreasing the osmolarity of the test solution by 75% (p = 0.24, p = 0.10, p = 0.39, respectively). We conclude that an increased intestinal permeability in CF is probably a consequence of PI and is not related to the dose of pancreatic enzyme supplementation nor the osmolarity of the test solution. The increase is due to an increased permeability for lactulose which might point toward a defect in the tight junctions of the villi and/or crypts. The cause of the increased intestinal permeability in the presence of PI is still unclear. An increased intestinal permeability points toward an impaired functional integrity of the small bowel, which may contribute to gastrointestinal dysfunction in CF.

Follow-up of treated coeliac patients: sugar absorption test and intestinal biopsies compared.

OBJECTIVE: To determine whether the sugar absorption test (SAT) during follow-up of patients with coeliac disease on a gluten-free diet (GFD) correlates with improvement of the villous architecture of the small intestine. METHODS: The SAT was performed in coeliacs at diagnosis and during follow-up with GFD. For the SAT, a solution of lactulose (L) and mannitol (M) was given to the fasting patient and the L-M ratio calculated in a 5-hour urine sample by gas chromatography: ratios > 0.089 are considered abnormal. The solution was made hyperosmolar by adding sucrose (1560 mmol/l). RESULTS: The L-M ratio was 2-3 times higher at diagnosis than either at 8 months to 2 years gluten free, or beyond 2 years gluten free, consecutively. The L-M ratio (mean, range) was significantly higher in cases of biopsies with (sub)total villous atrophy (VA) (0.388, 0.062-0.804, n = 28), partial VA (0.240, 0.062-0.841, n = 18) and villous irregularity (0.143, 0.017-0.322, n = 29) than in case of normalized histology after GFD (0.085, 0.021-0.230, n = 19). The rate of normalization of functional integrity was slower in adults than in children, demonstrated by a combination of histology and SAT. CONCLUSION: The SAT correlates well with the degree of VA. It is important for daily clinical practice that the simple and non-invasive SAT can be used as an indicator of intestinal damage, thus influencing need for and timing of intestinal biopsies.

Repeatability of the sugar-absorption test, using lactulose and mannitol, for measuring intestinal permeability for sugars.

Differential sugar-absorption tests for measuring intestinal permeability for sugars have been studied in a variety of gastrointestinal diseases. Their use in general practice has been hampered by a lack of data on reference values and repeatability of the test and the laboratory assay. In this study, we determined the reference values of the sugar-absorption test, using lactulose and mannitol as probe molecules, for children and adults. The repeatability of the test is good; linear relationship: slope, 0.825 [95% confidence interval (CI), 0.571, 1.152); intercept, 0.005 (95% CI, -0.004, 0.010). The repeatability of the laboratory assay for the sugar-absorption test is excellent; linear relationship: slope, 1.014 (95% CI, 0.870, 1.094); intercept, 0.002 (95% CI, -0.005, 0.010). The validation of the sugar-absorption test makes the test useful as a simple, noninvasive, reliable intestinal permeability test for sugars, which can be of use for clinical practice. Taking possible interfering factors into account, the sugar-absorption test can be used as a diagnostic test for enteropathy of different etiologies and evaluation of therapeutic interventions in both children and adults. Studies with the sugar-absorption test may clarify the role of intestinal permeability in the pathophysiology of a variety of gastrointestinal diseases.

[Measurement of selective intestinal permeability using a new, simple sugar absorption test]. / Meting van de selectieve darmpermeabiliteit met een nieuwe, eenvoudige suikerabsorptietest.

OBJECTIVE: To study the clinical value of the sugar absorption test (SAT) as a function test of the selective permeability of the small intestine in various intestinal diseases. DESIGN: Inventory of the results of the SAT in a number of patient groups and controls. SETTING: Beatrix Children's Hospital, Groningen and Rijnstate Hospital, Arnhem. METHODS: The SAT was performed in 51 controls (25 children, 26 adults) and in a number of diseases: (suspected) allergy to cow's milk albumin (30 children), (suspected) coeliac disease (86 children and 35 adults), Crohn's disease (25 patients) with ulcerative colitis (9), and pancreatic insufficiency (31) due to cystic fibrosis or chronic pancreatitis. For the SAT, the fasting patient is given a solution of mannitol (M) and lactulose (L) following which the L/M ratio, as an indicator of the selective intestinal permeability, is determined in 5-hour urine by means of gas chromatography. RESULTS: In cow's milk protein allergy, the L/M ratio showed a statistically significant increase in clinically positive cow's milk provocation results, unlike that in clinically negative results. After pretreatment with cromoglycate this difference decreased to non-significant values. The L/M ratio was increased in active coeliac disease (with villous atrophy), first-degree relatives of coeliac disease patients, Crohn's disease, clinically active ulcerative colitis and pancreatic insufficiency. The L/M ratio was not increased in inactive coeliac disease (with normal villi), suspicion of coeliac disease because of short stature, dystrophy and/or aspecific gastrointestinal symptoms with normal villi, and in clinically inactive ulcerative colitis. CONCLUSION: The selective intestinal permeability can be determined by means of the SAT. This could be an important tool for diagnosis and evaluation of therapy in gastrointestinal disorders.

Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease.

The functional integrity of the small bowel is impaired in coeliac disease. Intestinal permeability, as measured by the sugar absorption test probably reflects this phenomenon. In the sugar absorption test a solution of lactulose and mannitol was given to the fasting patient and the lactulose/mannitol ratio measured in urine collected over a period of five hours. The sugar absorption test was performed in nine patients with coeliac disease with an abnormal jejunum on histological examination, 10 relatives of patients with coeliac disease with aspecific symptoms but no villous atrophy, six patients with aspecific gastrointestinal symptoms but no villous atrophy, and 22 healthy controls to determine whether functional integrity is different in these groups. The lactulose/mannitol ratio (mean (SEM) is significantly higher in both coeliac disease (0.243 (0.034), p < 0.0001)) and relatives of patients with coeliac disease (0.158 (0.040), p < 0.005)) v both healthy controls (0.043 (0.006)) and patients with aspecific gastrointestinal symptoms (0.040 (0.011)). The lactulose/mannitol ratio in relatives of coeliac disease patients was significantly lower than in the coeliac disease patient group (p = 0.04). The lactulose/mannitol ratio was the same in healthy controls and patients with aspecific gastrointestinal symptoms. It is concluded that the sugar absorption test is a sensitive test that distinguishes between patients with coeliac disease and healthy controls. The explanation for the increased permeability in relatives of patients with coeliac disease is uncertain. Increased intestinal permeability may be related to constitutional factors in people susceptible to coeliac disease and may detect latent coeliac disease. The sugar absorption test may therefore be helpful in family studies of coeliac disease.

Coeliac disease. Diagnostic and therapeutic pitfalls.

Gluten-free diet (GFD) as the standard treatment for coeliac disease (CD) was discovered by Dicke. In 1989 Holmes attributed a protective role to GFD with regard to the development of malignancy in untreated CD. Gluten sensitivity is in general an asymptomatic condition. The identification of subclinical cases is becoming a major topic of current interest. Defining high-risk groups for coeliac disease is mandatory. The evaluation of small-intestine biopsies (SIB), however, is much more complicated, as was suggested in the past. Recognition of the Corazza sign and rediscovery of the endoscopic guided capsule may well be of help. Screening patients with a high-risk of CD with a minimal number of tests prior to SIB makes more and more sense. Therefore intestinal permeability tests might be helpful. GFD appears simple, but in practice it represents a challenge to patients, dietitians and physicians. Management of coeliac disease seems much more complicated, as was thought in the early 1980s.

Intestinal permeability in pediatric gastroenterology.

The role of the physiologic barrier function of the small bowel and its possible role in health and disease has attracted much attention over the past decade. The intestinal mucosal barrier for luminal macromolecules and microorganism is the result of non-immunologic and immunologic defense mechanisms. The non-immunologic mechanisms consist of intraluminal factors such as gastric acid, proteolytic activity, and motility and of mucosal surface factors like mucin and the microvillous membrane. The immunologic mechanisms include secretary IgA and cell-mediated immunity. Both types of mechanism are not completely mature at birth. Maturation of this barrier is not finished before the 2nd year of life. One of the aspects of the mucosal barrier function can be estimated by the intestinal permeability (IP) for macromolecules. We use the differential sugar absorption test (SAT), in which the ratio of urinary excretion of a relatively large molecule, lactulose, is compared with that of a relatively small molecule, mannitol, after oral ingestion. Although the small intestine is permeable to certain macromolecules in normal developmental conditions, an increased IP could be involved in the pathophysiology of several diseases, including infectious diarrhea, food allergy, celiac disease, and Crohn's disease. It can be concluded that IP, as measured with the SAT, reflects the state of the mucosal barrier and is altered in several gastrointestinal diseases. The SAT is a non-invasive IP test that can be of diagnostic help to demonstrate alterations in the small-mucosal barrier function and may be useful to evaluate therapeutic interventions.(ABSTRACT TRUNCATED AT 250 WORDS)