Ian S. Menzies

Cardiopulmonary bypass impairs small intestinal transport and increases cut permeability

Gastrointestinal damage occurs in 0.6% to 2% of patients after cardiopulmonary bypass (CPB), and carries a mortality of 12% to 67%. The incidence of subclinical gastrointestinal damage may be much greater. We examined the effects of nonpulsatile, hypothermic CPB on intestinal absorption and permeability in 41 patients. Bowel mucosal saccharide transport and permeation were evaluated using 100 mL of an oral solution containing 3-O-methyl-D-glucose (0.2 g), D-xylose (0.5 g), L-rhamnose (1.0 g), and lactulose (5.0 g) to assess active carrier-mediated, passive carrier-mediated, transcellular, and paracellular transport, respectively, with a 5-hour urine analysis. Patients were studied before, immediately after, and 5 days after CPB. Immediately after CPB there was a decrease in urinary excretion of 3-O-methyl-D-glucose (from 34% +/- 2.2% to 5.2% +/- 0.7%; p < 0.0001), D-xylose (from 25.4% +/- 1.4% to 4.1% +/- 0.8%; p < 0.0001), and L-rhamnose (from 8.3% +/- 0.6% to 2.6% +/- 0.4%; p < 0.0001). The permeation of 3-O-methyl-D-glucose and D-xylose returned to normal levels 5 days after CPB, but that of L-rhamnose remained significantly below pre-CPB values at 6.6% +/- 0.5% (p = 0.004). However, the permeation of lactulose increased after CPB (from 0.35% +/- 0.04% to 0.59% +/- 0.1%; p = 0.018), and the lactulose/L-rhamnose gut permeability ratio increased markedly (from 0.045 +/- 0.04 to 0.36 +/- 0.08; normal = 0.06 to 0.08; p = 0.004). Patients who had a CPB time of 100 minutes or more had a greater increase in gut permeability (p = 0.049).(ABSTRACT TRUNCATED AT 250 WORDS)

Misoprostol reduces indomethacin-induced changes in human small intestinal permeability

This study examined whether indomethacin-induced increases in small intestinal permeability in man are prevented by concomitant administration of a prostaglandin analog (misoprostol). Twelve male volunteers were tested as baseline, following misoprostol alone (200 Μg, at −16, −12, −8.5, −4, −1.5, and +4 hr); following indomethacin alone (75 mg, at −8; 50 mg, −1 hr); and following coadministration of misoprostol and indomethacin as specified above. A 100-ml test solution containing 3-O-methyl glucose (0.2 g), D-xylose (0.5 g),l-rhamnose (1.0 g), and [51Cr]EDTA (100 ΜCi) was ingested at 8 AM, and a 5-hr collection made for marker analysis to assess active and passive carrier-mediated transport and trans- and intercellular permeation, respectively. Indomethacin increased the permeation of [51Cr]EDTA selectively, and this increase was significantly reduced by the coadministration of misoprostol. These changes were mirrored by changes in [51 Cr]EDTA-L-rhamnose urine excretion ratios, which indicates that paracellular permeability was specifically altered. This study supports the suggestion that NSAIDs alter intestinal permeability by a mechanism involving reduced prostaglandin synthesis and indicates that coadministration of misoprostol with NSAIDs may reduce the frequency and severity of NSAID-induced small intestinal inflammation.

The effect of intestinal hypoperfusion on intestinal absorption and permeability during cardiopulmonary bypass

BACKGROUND/AIMS Mean arterial pressure is reduced during hypothermic cardiopulmonary bypass. The aim of this study was to assess whether this was associated with intestinal hypoperfusion and whether it affected intestinal absorption and permeability. METHODS Twenty-six patients undergoing coronary artery bypass grafting underwent an intestinal absorption-permeability test involving ingestion of 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose. Ingestion took place 2 days before, within 3 hours, and 5 days after hypothermic cardiopulmonary bypass. Hemodynamic parameters and gastric mucosal laser Doppler blood flow were measured perioperatively in eight patients. RESULTS Hypothermic (28 degrees C), nonpulsatile cardiopulmonary bypass resulted in a 25% reduction in mean blood pressure, 10% reduction in cardiac index, and a 46% reduction in gastric mucosal laser Doppler blood flow. There was 85.4%, 85.5%, and 73.6% reduction (P < 0.01) in active (3-O-methyl-D-glucose) and passive (D-xylose) carrier-mediated transport and passive, nonmediated transcellular (L-rhamnose) transport in the immediate postoperative period, respectively. The differential urine excretion of lactulose/L-rhamnose increased sixfold. All parameters returned to control levels by the fifth postoperative day. CONCLUSIONS Cardiopulmonary bypass, while maintaining generally acceptable levels of hemodynamic performance, is associated with significant intestinal hypoperfusion and malabsorption of monosaccharides, which may have implications for enteral drug treatment in the immediate postoperative period.

Intestinal inflammation, ileal structure and function in HIV

Objectives:This study examines small intestinal absorption–permeability, intestinal inflammation and ileal structure and function in HIV-positive male homosexuals. Methods:Thirty HIV-seropositive male homosexuals at various stages of disease underwent intestinal absorption–permeability and 111indium leukocyte studies (for quantification of intestinal inflammation). Twenty-six men with AIDS had a dual radio-isotopic ileal function test (whole body retention of tauro 23-[75Se]-selena 25-homocholic acid and 58cobalt-labelled cyanocobalamine), and 17 underwent ileocolonoscopy with terminal ileal biopsy. Results:Well, HIV-infected, subjects had normal intestinal absorption–permeability, but both functions were impaired upon the development of AIDS. The median faecal excretion of 111 indium in well patients (0.66%) did not differ significantly (P > 0.5) from controls (0.46%), but subjects with AIDS who were well or who had diarrhoea had significant (P < 0.005) intestinal inflammation (1.33% and 2.18%, respectively). The median 7-day retention of tauro 23-[75Se]-selena 25-homocholic acid in well patients with AIDS (38.9%) did not differ significantly (P > 0.2) from controls (39.3%), whereas the absorption of 58cobalt-labelled cyanocobalamine was significantly (P < 0.05) lower than controls (32.1% and 59.4%). Patients with AIDS-diarrhoea had significant (P < 0.001) malabsorption of both the bile acid (7.7%) and vitamin B12 (8.9%) which was more severe than in Crohns ileitis (14.2% and 30.3%, respectively). Morphometric analyses of ileal biopsies were unremarkable in AIDS. Conclusions:These studies demonstrate a low-grade enteropathy in patients with AIDS, severe ileal malabsorption in patients with AIDS diarrhoea and relatively minor ileal morphologic changes. Malabsorption of bile acids may play a pathogenic role in patients with AIDS and diarrhoea.

Assessment of Intestinal Permeability and Absorption in Cirrhotic Patients with Ascites Using Combined Sugar Probes

Gastrointestinal dysfunction in patients with cirrhosis may contribute to complications such as malnutrition and spontaneous bacterial peritonitis. To determine whether cirrhotic patients with ascites have altered intestinal function, we compared intestinal permeability and absorption in patients with liver disease and normal subjects. Intestinal permeability and absorption were investigated in 66 cirrhotic patients (48 with ascites, 18 without ascites) and 74 healthy control subjects. Timed recovery of 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in urine following oral administration was measured in order to assess active and passive carrier-mediated, and nonmediated, absorptive capacity, as well as intestinal large-pore/small-pore (lactulose/rhamnose) permeability. Test sugars were measured by quantitative thin-layer chromatography and results are expressed as a percentage of test dose recovered in a 5-h urine collection. Sugar excretion ratios relating to small intestinal permeability (lactulose/rhamnose) and absorption (rhamnose/3-O-methyl-D-glucose) were calculated to avoid the effects of nonmucosal factors such as renal clearance, portal hypertension, and ascites on the recovery of sugar probes in urine. Compared with normal subjects, the mean lactulose/rhamnose permeability ratio in cirrhotic patients with ascites was significantly higher (0.058 vs. 0.037, P < 0.001) but not in cirrhotic patients without ascites (0.041 vs. 0.037). Cirrhotic patients with ascites had significantly lower mean recoveries of 3-O-methyl-D-glucose (23.0 vs. 49.1%; P < 0.001), D-xylose (18.8 vs. 34.5%; P < 0.001), L-rhamnose (4.0 vs. 9.1%; P < 0.001), and lactulose (0.202 vs. 0.337%; P < 0.001) than normal subjects. However, the mean rhamnose/3-O-methyl-D-glucose ratio was the same in cirrhotic patients with ascites as normal subjects (0.189 vs. 0.189), indicating that the reduction in probe recovery was due to nonmucosal factors. Compared with normal subjects, cirrhotic patients with ascites have abnormal intestinal permeability, measured by urinary lactulose/rhamnose excretion, and normal small intestinal absorption, assessed by the urinary rhamnose/3-O-methyl-D-glucose ratio. Low urine recovery of sugar probes found in cirrhotic patients appears to be the result of nonintestinal factors affecting clearance rather than reduced intestinal absorption.

Energy balance in asymptomatic HIV infection.

Objectives:Body weight is regulated by the balance between energy intake and energy expenditure, but the influence of HIV infection on energy balance has not been fully examined. The main objectives of this study were (1) to assess the effect of HIV on energy balance, (2) to examine the relationship of parameters of immunodeficiency to energy balance, and (3) to examine the interrelationship of different components of energy balance in asymptomatic HIV-seropositive men. Design:A cross-sectional study of nutrition and metabolism in asymptomatic HIV-seropositive men. Methods:Components of energy balance were examined in 104 asymptomatic HIV-seropositive men (CD4 count 4–482×106/l) and 57 age-matched HIV-seronegative male controls. Energy and protein intake were measured using 5-day diaries, and small bowel absorption and permeability was assessed using four sugar probes. Resting energy expenditure was calculated from indirect calorimetry and nitrogen loss estimated from 24 h urine collection. Four methods were used to assess the effect of HIV infection on body composition (anthropometry, dual energy X-ray absorptiometry, bioelectrical impedance and 24 h urine creatinine). Results:Resting energy expenditure per kilogram of fat-free mass was raised (P < 0.0001), fat mass was decreased (P = 0.001), fat-free mass was increased (P = 0.05), energy intake was higher (P = 0.05), absorption of L-rhamnose (P = 0.01) and 3-O-methyl-D-glucose was decreased (P = 0.003), and small bowel permeability was increased (P < 0.0001) in HIV-seropositive men compared with HIV-seronegative controls. HIV-seropositive subjects with a CD4 count less than 100×106/l had decreased absorption of L-rhamnose (P < 0.05), D-xylose (P < 0.05) and 3-O-methyl-D-glucose (P < 0.05) compared with HIV-seropositive subjects at higher CD4 counts, and had a similar resting energy expenditure to HIV-seronegative controls. Protein intake, carbohydrate, fat and protein oxidation, 24 h nitrogen excretion and appendicular muscle mass were similar in HIV-seropositive men and controls. Conclusion:HIV infection exerts a direct effect on parameters of energy balance that varies with the severity of immunosuppression.

Intestinal permeability in Crohn's disease and its relation to disease activity and relapse following treatment with an elemental diet

Objective To assess the relationship between clinical disease activity, intestinal permeability and intestinal inflammation in patients with small intestinal Crohns disease. Methods Twenty-nine patients with small intestinal Crohns disease were assessed clinically and underwent permeability studies with iso-, hyper- and hypo-osmolar test solutions and indium-111 leucocyte studies, which involved faecal collections over 4 days, to quantify intestinal inflammation. Thirteen patients were re-studied following treatment with an elemental diet and followed-up to assess whether any of the parameters could predict early relapse following this treatment. Results There was a noticeable lack of correlation between clinical disease activity, increased intestinal permeability and intestinal inflammation. Although all the patients improved significantly during treatment with an elemental diet, there was no significant correlation between the degree of improvement assessed by the three techniques. However, increased intestinal permeability at the end of treatment predicted early relapse. Conclusions Most patients with active small intestinal Crohns disease have increased intestinal permeability and increased faecal excretion of indium-111 neutrophils. Neither correlated significantly with clinical disease activity. All appear suitable to assess response to treatment. Increased intestinal permeability following treatment with an elemental diet may identify patients who are prone to early relapse.

Intestinal Permeability: The Basics

Twenty years ago it became possible, with the introduction of nonmetabolized sugars as test substances, to assess intestinal permeability reliably and noninvasively in humans1. Acceptance of the technique was initially slow, mainly because of the confusion that the use of polyethylene glycol (PEG 400) brought with it2,3, but in the past few years there has been a proliferation of published studies, from a wide range of research workers, using these tests to assess various aspects of gastrointestinal diseases. Tests of intestinal permeability may relate to at least five purposes; these are: 1. Diagnostic screening for intestinal disease. 2. Confirming diagnosis; indication of therapeutic response and prognosis. 3. Evaluation of drug-related, dietary and environmental factors upon the intestine. 4. The effect of various physiological factors on intestinal barrier function; for instance, related to diet (e.g. level of food intake and osmolar content), level of nutrition and state of blood flow. 5. To assess the importance of the intestinal barrier function in the etiology, pathophysiology and pathogenesis of intestinal and systemic disease.

Lower gastrointestinal bleed in a patient with typhoid fever

malignancy. The lesion was identified on the greater curvature of stomach and was locally excised with a margin of normal tissue. There was no communication with the lumen of the stomach. Histological examination revealed characteristic features of GDC (2). The cyst wall was composed of the epithelial layer, lamina propria, and inner muscle layer. The epithelial layer comprised ciliated, pseudostratified columnar epithelium and gastric foveolar epithelium without evidence of malignancy. Immunohistochemical analysis revealed CA19-9 staining–positive cells in the epithelium. The patient had an uneventful recovery and remains well 6 months after operation. GDC is extremely rare in the adult population (1), and it is often difficult to discriminate it from malignant cystic tumors. It is usually diagnosed by surgery because of unspecified symptoms and rarity (3). Our patient remained asymptomatic until adulthood although he had the large GDC. In addition to its size, the fluid analysis revealed markedly elevated concentration of CA19-9. GDC is always benign in the pediatric population (4). However, malignant transformation has been described in a few adult cases (5). Surgical removal should be considered for even an asymptomatic GDC once it is diagnosed.