Intestinal Permeability In Patients Research Articles

Intestinal permeability in patients with acute myeloid leukemia.

Intestinal permeability was studied in patients with acute myeloid leukemia (AML) before, during and after chemotherapy. Intestinal permeability was determined by the lactulose (La)/mannitol (Ma) absorption test in 16 adult patients with de novo AML. The hydrogen breath test was used to disclose bacterial fermentation of the test substances in the small intestine. The permeability was found significantly increased (p<0.02) in the patients before induction chemotherapy treatment. During induction treatment and throughout the cytopenic period the intestinal permeability was constantly and significantly increased, compared with controls. In patients with abnormally increased permeability, no increase in hydrogen breath test result was noted. From our results it can be concluded that increased intestinal permeability is present in AML patients before commencing chemotherapy. Factors other than chemotherapy would seem to be more important regarding the occurrence of intestinal disturbances in these patients.

A double-blind placebo-controlled pilot study of glutamine therapy for abnormal intestinal permeability in patients with AIDS

Objectives: Up to 20% of patients with AIDS have abnormal intestinal permeability (IP). Glutamine seems to play an important role in preventing the increase in IP and loss of intestinal mucosal mass associated with total parenteral nutrition, and may be superior to glucose for oral rehydration in the setting of intestinal infection. This study was designed to see if supplemental glutamine could alter the abnormal IP of AIDS. Methods: Randomly chosen patients with AIDS from the Jacobi Medical Center human immunodeficiency virus (HIV) clinic underwent IP testing using lactulose and mannitol. Those with abnormal IP were enrolled. Duodenal biopsies were performed with a Crosby capsule and the patients were randomized in a double-blind fashion to receive placebo or glutamine (4 g/day or 8 g/day) for 28 days, after which intestinal permeability tests and duodenal biopsies were repeated. Intestinal morphology was graded by ratio of villus height to crypt depth, and by degree of inflammation. Results: All patients complied with the therapy and there were no dropouts or reported side effects. The results showed less worsening of IP with the 4 g/day dose, compared with placebo. At the 8 g/day dose, there was stabilization of IP and improved absorption of mannitol. Intestinal morphology and inflammation did not change in any group. Conclusions: These results, although not significant, suggest a trend towards improved IP and enhanced intestinal absorption with glutamine. Glutamine doses of at least 20 g/day may be necessary to improve IP. We recommend further studies at higher doses and for longer durations.

Small intestinal permeability in patients with Crohn's disease and their first-degree relatives

Small intestinal permeability in patients with Crohn's disease and their first-degree relatives

757 - Effect of chemotherapy with 5-fluorouracil on intestinal permeability of patients with advanced colon cancer

757 - Effect of chemotherapy with 5-fluorouracil on intestinal permeability of patients with advanced colon cancer

Colchicine enhances intestinal permeability in patients with familial Mediterranean fever.

Colchicine therapy is complicated by frequent gastrointestinal adverse effects. We compared intestinal permeability in 21 patients with familial Mediterranean fever on long-standing colchicine therapy (mean 5.8 years) and significant gastrointestinal complaints and 12 untreated patients and 14 healthy volunteers. The double probe (lactulose/mannitol) permeability test was performed using a hyperosmolar test solution (1580 mosmol) and the differential urinary recovery ratios were calculated. Familial Mediterranean fever patients on colchicine therapy had significantly higher lactulose/mannitol urinary excretion ratios (0.073) compared to untreated patients (0.035) and to healthy controls (0.021). Untreated familial Mediterranean fever patients had significantly greater urinary lactulose/mannitol recovery ratios than controls (P < 0.02). No correlation was found between the degree of enhanced permeability and the length of exposure to the drug or the severity of clinical symptoms. Intestinal permeability was significantly enhanced in patients with familial Mediterranean fever treated with colchicine.

EXTRAINTESTINAL CONSIDERATIONS IN INFLAMMATORY BOWEL DISEASE

If one reviews the literature with zeal, it is increasingly apparent that few organs escape recruitment when IBD is chronic or progressive. Insights into mucosal pathophysiology have helped with understanding the more frequent extraintestinal manifestations, but the mechanisms attendant to the development of less common events (e.g. acute pancreatitis, concurrent gluten sensitive enteropathy, or active pulmonary disease) remain either poorly studied or obscure. It is particularly interesting, however, to read reports of abnormal pulmonary function, generally of the obstructive type, correlated to measurements of abnormal intestinal permeability in patients with either active pulmonary sarcoid or pulmonary involvement in Crohn's disease. It has been further speculated that similarities in the mucosal immune system of the lung and intestine are responsible for evidence of bronchial hyperreactivity in patients with active IBD. Finally, it is important to recognize that extensions of the inflammatory process are not restricted to the development of organ-based events but may be responsible for some of the most frequent systemic abnormalities detected in IBD patients. It is now also well confirmed that the cytokine environment in IBD can support activated coagulation and, in some clinical situations, overt vascular thrombosis. The cerebrovascular complications of IBD are well recognized and range from peripheral venous thrombosis to central stroke syndromes and pseudotumor cerebri. Reports of focal white matter lesions in the brains of patients with IBD or an increased incidence of polyneuropathy may be other clinical examples of regional microvascular clotting. Microvascular injury appears to be more ubiquitously present, with reports ranging from a speculated primary causative role (e.g., granulomatous vasculitis in the mesenteric circulation) to the utility of nailbed vasospasm, in Crohn's disease, as a clinical marker for disease activity. It is also reported that IL-6 suppression of erythropoietin production is a major feature of the chronic anemia seen in active IBD. Moreover, the capacity of peripheral monocytes from active IBD patients to secrete TNF and IL-8 is reported predictive for the degree of therapeutic response from recombinant erythropoietin. These collected observations constitute another excellent example of the symmetry between basic science and clinical utility. It is from the context of applied basic science that many future therapies will arise. Empiricism will lose much of its appeal as clinical observations will be increasingly translated into cellular language. Already in animal models, elemental diets diminish IL-6-related acute inflammatory injury, and reductions in dietary lipid alter the antigenicity of bacteria. Provocatively, in humans, unconfirmed reports have even associated diet therapy with the resolution of uveitis and pyoderma gangrenosum. It is likely that efforts will also be made to induce oral tolerance if specific triggering proteins are discovered or to alter bowel flora if such an arcane area of investigation becomes resurgent.

Evaluation of intestinal permeability in patients with inflammatory bowel disease using lactulose and measuring antibodies to lipid A.

This study looked at the intestinal permeability and the immune response to enteric bacterial antigens in patients with inflammatory bowel disease (IBD). They were evaluated by using a lactulose tolerance test and measuring blood anti-lipid A antibody concentrations, respectively. The lactulose tolerance tests were performed 22 times in 14 patients with Crohn's disease (CD), 19 times in 12 patients with ulcerative colitis (UC), and 12 times in 12 healthy controls. Blood lactulose concentrations were measured after oral administration every two hours for eight hours, also blood C reactive protein concentrations and anti-lipid A antibody concentrations were measured just before lactulose administration. Blood lactulose concentrations were significantly higher in patients with CD than in the controls from two to eight hours after administration, while in UC they were significantly higher than in the controls from six to eight hours. Maximum blood lactulose concentrations in each tolerance test in patients with the active phase significantly exceeded those in the inactive phase of either CD or UC. A significant correlation was also seen between the maximum blood lactulose concentrations and the C reactive protein concentrations. Blood anti-lipid A antibody concentrations in patients with CD were significantly higher than in the controls as well as in patients with UC in immunoglobulin (Ig) A class and IgG class. In UC they were significantly higher than in the controls in IgA class. But, they were not related to the severity of the disease of either CD or UC, and not correlated significantly with the maximum blood lactulose concentrations in either CD or UC. The intestinal permeability and the immune response to enteric bacterial antigens in patients with inactive CD were significantly increased over those in the controls as well as in patients with inactive UC. These findings suggest that an increase of the intestinal permeability and that of producing antibodies to enteric bacterial antigens are both important for the pathogenesis of IBD, and that the characteristics of CD and UC differ.

Intestinal permeability in patients with Crohn's disease.

Intestinal permeability in patients with Crohn's disease.

Intestinal permeability in patients with Crohn's disease and ulcerative colitis and their first degree relatives.

Increased intestinal permeability in patients with Crohn's disease and their first degree relatives has been proposed as an aetiological factor. The nine hour overnight urinary excretion of polyethyleneglycol-400 (PEG-400) and three inert sugars (lactulose, l-rhamnose, and mannitol) was used to test the permeation in 47 patients with Crohn's disease of whom 18 had at least one first degree relative with inflammatory bowel disease (2BD) and 52 patients with ulcerative colitis of whom 16 had at least one first degree relative with IBD. A total of 17 first degree relatives with IBD and 56 healthy first degree relatives were included. Thirty one healthy subjects not related to patients with IBD served as controls. No significant differences in PEG-400 permeation were found between the groups of patients, relatives, and controls, or between diseased and healthy relatives. The permeability to lactulose, rhamnose, and mannitol similarly did not differ between the three groups. This study challenges the previously reported findings of increased PEG-400 permeation in patients with Crohn's disease and in their healthy and diseased first degree relatives. There was no increase in permeability in a similar group of ulcerative colitis patients and their families.

Serologic and histologic markers of coeliac disease (CD) and intestinal permeability in patients with primary biliary cirrhosis (PBC)

Serologic and histologic markers of coeliac disease (CD) and intestinal permeability in patients with primary biliary cirrhosis (PBC)

Intestinal permeability is increased after major vascular surgery

Purpose: In experimental animals increased intestinal permeability has been demonstrated after ischemia and reperfusion injury. In this study we determined intestinal permeability in patients after elective or emergency aortic aneurysm repair the latter patients were in severe shock on hospital admission.Methods: A dual sugar absorption test, with lactulose and mannitol as markers, was used to measure intestinal permeability on the second day between 24 and 30 hours after hospital admission.Results: The lactulose/mannitol excretion ration was 0.012 ± 0.005 in seven healthy control subjects, 0.118 ± 0.116 in seven patients having elective operation, and 0.098 ± 0.093 in eight patients having emergency operation, indicating a significant increase of intestinal permeability in both patient groups (p < 0.01). No significant difference was found in intestinal permeability between patients of the elective and emergency groups.Conclusions: A significant increase in intestinal permeability commonly occurs in patients after elective and emergency major vascular surgery. It is suggested that this is mainly due to reperfusion injury rather than the ischemic period of the intestine itself.

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.

Intestinal permeability in patients with Crohn's disease and their first degree relatives.

It has been reported that intestinal permeability to polyethylene glycol 400 is increased in patients with Crohn's disease and their apparently unaffected first degree relatives. Because of the implications that these findings have for the aetiology of Crohn's disease these studies were repeated. Patients with Crohn's disease (n = 28) and 32 first degree relatives from 11 families underwent a polyethylene glycol 400 (PEG400) intestinal permeability test and a hyperosmotic (1500 mosmol/l) absorption/permeability test using 3-0-methyl-D-glucose, D-xylose, L-rhamnose, lactulose, and 51chromium labelled ethylenediamine-tetraacetate. The five hour urine excretion of polyethylene glycol 400 did not differ significantly between controls (n = 25) and first degree relatives, 25.5 (3.3)% v 24.6% (4)% (mean(SD)) p greater than 0.1, respectively. Patients with small bowel involvement excreted significantly less (p less than 0.01) polyethylene glycol 400 (16.3 (4.6)% than controls while those with Crohn's colitis did not (26.4 (3.9)% p greater than 0.1). The permeation of the monosaccharides in patients with Crohn's disease and their first degree relatives did not differ from normal subjects. The permeation of lactulose and 51chromium ethylenediaminetetraacetate was not significantly altered in first degree relatives but was significantly increased in the patients, as was the lactulose/L-rhamnose urine excretion ratio which is a specific measure of small intestinal permeability. These studies show normal absorption and permeability in first degree relatives of patients with Crohn's disease. A genetically determined abnormality of intestinal permeability is not likely to be an important aetiological factor in Crohn's disease.

Intestinale Permeabilität bei Patienten mit erworbenem Immundefekt — Syndrom (AIDS)

Intestinal permeability has been assessed as a parameter of the small intestinal barrier function in 33 patients with AIDS (WR 6), in 25 healthy volunteers, 32 patients with Crohn's disease, 18 patients with ulcerative colitis and in 12 patients with untreated coeliac disease. Permeability was measured by means of the 5 hour urinary excretion of lactulose and rhamnose after administration of these sugars (1 g rhamnose, 10 g lactulose) which allowed to calculate the urinary lactulose/rhamnose--ratio (L/R-r) as an index of intestinal permeability. Compared to the controls (L/R-r = 0.014 +/- 0.010) patients with AIDS had significantly increased lactulose/rhamnose--ratios (0.189 +/- 0.164; p less than 0.01) indicating abnormal permeation both of lactulose and rhamnose. This alteration of intestinal permeability was more pronounced than the significant increase of the L/R-r in the patients with either Crohn's disease or coeliac disease. However, intestinal permeability was not altered in the patients with ulcerative colitis. Among the patients with AIDS, the most abnormal permeability ratios were observed in two subjects with intestinal cryptosporidiosis. This investigation demonstrates by means of the "double sugar ratio", that intestinal permeability in patients with AIDS is highly abnormal, the impairment being even more abnormal than in patients with other small intestinal disease.

Intestinal permeability in patients with psoriasis

A possible relationship between intestinal structure and function in the pathogenesis of psoriasis has recently brought about considerable interest. The purpose of this study was to evaluate the intestinal permeability in psoriatic patients by comparing it with healthy controls. 15 psoriatic patients and 15 healthy volunteers entered the study. Intestinal permeability was evaluated using the 51Cr-labeled EDTA absorption test. The 24-h urine excretion of 51Cr-EDTA from psoriatic patients was 2.46 ± 0.81%. These results differed significantly from controls (1.95 ± 0.36%; P < 0.05). The difference in intestinal permeability between psoriatic patients and controls could be due to alterations in the small intestinal epithelium of psoriatics.

Intestinal permeability in patients with yersinia triggered reactive arthritis.

The passive intestinal permeability of patients with yersinia triggered reactive arthritis was studied using different sized polyethylene glycols (PEGs) contained in a mixture of PEG 400 and PEG 1000. The investigation was carried out at least one year after the onset of yersinia infection, and patients had neither acute gastrointestinal nor joint symptoms. The control groups included patients with uncomplicated yersiniosis as well as healthy subjects who were either HLA-B27 positive or negative. An altered intestinal barrier function to PEG molecules was detected in patients with a history of yersinia infection compared with healthy controls. No significant differences in the permeability were found between patients with or without reactive arthritis, nor was there any association of increased permeability with HLA-B27. The passive permeability of the intestinal mucosa to the larger molecules was increased for an unexpectedly long time after the acute yersinia infection, probably contributing to the perpetuation of joint symptoms in subjects susceptible to a chronic joint disease.

Intestinal mast cells and neutrophil chemotactic activity of serum following a single challenge with gluten in celiac children on a gluten-free diet.

The number of one subtype of mast cells (formalin fixation, toluidine blue staining), cells of the lamina propria, and intraepithelial lymphocytes were counted in the intestinal biopsy specimens of 14 children with treated celiac disease following a single challenge with gluten. The serum neutrophil chemotactic activity was measured at 0, 1, 3, 5, and 24 h after challenge. There was no significant change in the number of intraepithelial lymphocytes, but the biopsy samples obtained at 5 h showed a marked increase in the inflammatory cells of the lamina propria and a significant decrease in the number of mast cells. A pronounced decrease was present at 3-5 h in the number of eosinophil cells in the blood. The neutrophil chemotactic activity of sera showed a significant increment in 10 of 14 patients. The intestinal permeability of patients became abnormal, as detected by the increased absorption of lactulose. These findings suggest that degranulation of mast cells may be involved in the pathogenesis of the small intestinal mucosal injury in children with celiac disease.

Intestinal permeability in patients with Crohn's disease and their healthy relatives

The healthy relatives of patients with Crohn's disease were previously found to have increased intestinal permeability to polyethylene glycol 400. To determine whether the abnormal permeability is uniquely detectable by polyethylene glycol 400, we studied the intestinal permeability of three new probes (lactulose, rhamnose, and mannitol) in 25 patients with Crohn's disease, 41 of their healthy relatives, and 29 normal controls without a family history of inflammatory bowel disease. Patients with Crohn's disease had increased lactulose permeability when compared with relatives or controls. Lactulose absorption by patients with Crohn's disease was 0.41% ± 0.07% (mean ± SE), whereas that of their relatives and unrelated controls was 0.28% ± 0.03% and 0.26% ± 0.03%, respectively. There was no significant difference between the relatives and controls, but both groups differed from the patients (p < 0.05 and p < 0.025, respectively). The patients' lactulose/rhamnose ratio was 70.5% ± 9.2% vs. 37.2% ± 3.3% in relatives and 40.6% ± 5.7% in unrelated controls (p < 0.0005 and p < 0.0025, respectively). The two intermediate-sized probes, rhamnose and mannitol, did not detect permeability differences among the three groups. The inability of lactulose, rhamnose, or mannitol to detect permeability abnormalities in healthy relatives of patients with Crohn's disease suggests that these probes penetrate the intestinal barrier by routes or mechanisms that are different from those of polyethylene glycol 400. Lactulose, in particular, detects permeability changes in patients with intestinal inflammation, and polyethylene glycol 400 is able to detect permeability changes in the healthy relatives of our patients. These data indicate that permeability may be abnormal as a secondary result of inflammation, or as a result of a primary genetic abnormality.

Intestinal Mast Cells and Neutrophil Chemotactic Activity of Serum Following a Single Challenge with Gluten in Celiac Children on a Gluten‐Free Diet

The number of one subtype of mast cells (formalin fixation, toluidine blue staining), cells of the lamina propria, and intraepithelial lymphocytes were counted in the intestinal biopsy specimens of 14 children with treated celiac disease following a single challenge with gluten. The serum neutrophil chemotactic activity was measured at 0, I, 3, 5, and 24 h after challenge. There was no significant change in the number of intraepithelial lymphocytes, but the biopsy samples obtained at 5 h showed a marked increase in the inflammatory cells of the lamina propria and a significant decrease in the number of mast cells. A pronounced decrease was present at 3–5 h in the number of eosinophil cells in the blood. The neutrophil chemotactic activity of sera showed a significant increment in 10 of 14 patients. The intestinal permeability of patients became abnormal, as detected by the increased absorption of lactulose. These findings suggest that degranulation of mast cells may be involved in the pathogenesis of the small intestinal mucosal injury in children with celiac disease.

Intestinal permeability in Crohn's disease.

Crohn's disease may present insidiously, especially in childhood, and diagnosis may be delayed. In addition, the clinical assessment of the extent of disease activity may be inaccurate. Using mannitol and lactulose as probe molecules we have carried out a cross sectional study of intestinal permeability in patients with active Crohn's disease (n = 17) and control subjects (n = 31). Activity was assessed by an activity index score. The lactulose:mannitol urinary excretion ratio was significantly increased in Crohn's disease. Overall sensitivity was 82%, and 92% when activity was moderate or severe. When permeability was compared with the activity index there was a significant correlation among patients. In five patients studied longitudinally a significant correlation was also present. Measurement of intestinal permeability is non-invasive, and may be useful both as a screening test in patients with non-specific symptoms, and for the assessment of the extent of disease activity in patients with Crohn's disease.