Eduardo Garcia Vilela

Influence of Saccharomyces boulardii on the intestinal permeability of patients with Crohn's disease in remission.

Objective. Crohns disease (CD) is characterized by a reduction in mucosal integrity that permits antigen penetration into the intestinal tissue. The administration of probiotics has been suggested to improve the barrier function of the mucosa. The objective of this study was to evaluate the influence of Saccharomyces boulardii on the intestinal permeability in CD. Material and methods. Thirty-four patients were randomized according to the Vienna classification for treatment with either placebo or Saccharomyces boulardii. Baseline medications (mesalamine, azathioprine, prednisone, metronidazole and/or thalidomide) were maintained. Intestinal permeability (lactulose/mannitol ratio) was evaluated immediately before the beginning of treatment and at the end of the first and third treatment month. Fifteen healthy volunteers were also submitted for the intestinal permeability test. Results. In volunteers, the lactulose/mannitol ratio was 0.005±0.0037, whereas this value was 0.021±0.01 in patients with CD (p=0.001). In the placebo group, there was an increase in lactulose/mannitol ratio by 0.004±0.010 (p=0.12) at the end of the third month. In the S. boulardii group, there was an improvement in intestinal permeability, with a decrease in the lactulose/mannitol ratio by 0.008±0.006 (p=0.0005) in the same period. Conclusions. Patients with CD in remission present alterations in the integrity of the intestinal mucosal barrier according to lactulose/mannitol ratio. S. boulardii added to baseline therapy improved intestinal permeability in these patients, even though complete normalization was not achieved.Objective. Crohns disease (CD) is characterized by a reduction in mucosal integrity that permits antigen penetration into the intestinal tissue. The administration of probiotics has been suggested to improve the barrier function of the mucosa. The objective of this study was to evaluate the influence of Saccharomyces boulardii on the intestinal permeability in CD. Material and methods. Thirty-four patients were randomized according to the Vienna classification for treatment with either placebo or Saccharomyces boulardii. Baseline medications (mesalamine, azathioprine, prednisone, metronidazole and/or thalidomide) were maintained. Intestinal permeability (lactulose/mannitol ratio) was evaluated immediately before the beginning of treatment and at the end of the first and third treatment month. Fifteen healthy volunteers were also submitted for the intestinal permeability test. Results. In volunteers, the lactulose/mannitol ratio was 0.005±0.0037, whereas this value was 0.021±0.01 in patients with CD (p=0....

Evaluation of inflammatory activity in Crohn’s disease and ulcerative colitis

Crohns disease and ulcerative colitis evolve with a relapsing and remitting course. Determination of inflammatory state is crucial for the assessment of disease activity and for tailoring therapy. However, no simple diagnostic test for monitoring intestinal inflammation is available. Noninvasive markers give only indirect assessments of disease activity. Histopathological or endoscopical examinations accurately assess inflammatory activity, but they are invasive, time consuming and expensive and therefore are unsuitable for routine use. Imaging procedures are not applicable for ulcerative colitis. The usefulness of ultrasound and Doppler imaging in assessing disease activity is still a matter of discussion for Crohns disease, and an increased interest in computed tomography enterograph (CTE) has been seen, mainly because it can delineate the extent and severity of bowel wall inflammation, besides detecting extraluminal findings. Until now, the available data concerning the accuracy of magnetic resonance enterography in detecting disease activity is less than CTE. Due to this, clinical activity indices are still commonly used for both diseases.

Gut permeability to lactulose and mannitol differs in treated Crohn's disease and celiac disease patients and healthy subjects

The gut barrier monitors and protects the gastrointestinal tract from challenges such as microorganisms, toxins and proteins that could act as antigens. There is evidence that gut barrier dysfunction may act as a primary disease mechanism in intestinal disorders. The aim of the present study was to evaluate the barrier function towards sugars after the appropriate treatment of celiac disease and Crohns disease patients and compare the results with those obtained with healthy subjects. Fifteen healthy volunteers, 22 celiac disease patients after 1 year of a gluten-free diet, and 31 Crohns disease patients in remission were submitted to an intestinal permeability test with 6.0 g lactulose and 3.0 g mannitol. Six-hour urinary lactulose excretion in Crohns disease patients was significantly higher than in both celiac disease patients (0.42 vs 0.15%) and healthy controls (0.42 vs 0.07%). Urinary lactulose excretion was significantly higher in celiac disease patients than in healthy controls (0.15 vs 0.07%). Urinary mannitol excretion in Crohns disease patients was the same as healthy controls (21 vs 21%) and these values were significantly higher than in celiac disease patients (10.9%). The lactulose/mannitol ratio was significantly higher in Crohns disease patients in comparison to celiac disease patients (0.021 vs 0.013) and healthy controls (0.021 vs 0.003) and this ratio was also significantly higher in celiac disease patients compared to healthy controls (0.013 vs 0.003). In spite of treatment, differences in sugar permeability were observed in both disease groups. These differences in the behavior of the sugar probes probably reflect different mechanisms for the alterations of intestinal permeability.

Intestinal permeability and antigliadin antibody test for monitoring adult patients with celiac disease.

Celiac disease causes chronic inflammation of the intestinal mucosa and reduces surface absorption; after the withdrawal of gluten from the diet, there are clinical and histologic improvements. The intestinal permeability test and serologic tests are useful for confirming the diagnosis and monitoring patients. The goal of this study is to compare the antigliadin antibody (AGA) test with the intestinal permeability test for celiac patients on a gluten-free diet. The sample consisted of 22 celiac patients who were antigliadin immunoglobulin A–positive before treatment. After 12 months on a gluten-free diet, AGA testing was repeated and the intestinal permeability test was performed. A control group was composed of 11 healthy individuals. AGA remained positive in 40.9% of celiac patients, and the mean urinary lactulose excretion was 10.27%, that of mannitol was 10.18%, and the lactulose/mannitol ratio was 1.02. In the subgroup in which antigliadin became negative (59.1%), the value for lactulose was 3.79%, that for mannitol was 11.12%, the lactulose/mannitol ratio was 0.38, and the p value was less than 0.0001, 0.66, and less than 0.0001, respectively. When the two celiac subgroups were compared with the control group, the urinary lactulose excretion and the lactulose/mannitol ratio was less in the control group, whereas urinary mannitol excretion was greater. The p values were less than 0.0001 for the three variables, suggesting persistent lesions in mucosa of both subgroups, although to a lesser degree for those that became AGA negative. It is concluded that intestinal permeability allows a more precise clinical physiopathologic correlation than antigliadin and offers more information for the monitoring of these patients.

Efficacy of glutamine-supplemented parenteral nutrition on short-term survival following allo-SCT: a randomized study

Fifty-three patients with hematological malignancies who underwent Allo-SCT from HLA-identical siblings were randomly assigned to receive glutamine-enriched parenteral nutrition—PN (GlPN, n=27) or standard PN (PN, n=26), in isonitrogenous solutions. Deaths (D+100 and D+180), infections, acute GVHD, length of stay, time of neutropenia and intestinal permeability (IP) were studied. Ages, gender, diagnosis, disease status and treatment variables were equally distributed between groups. Survival on D+180 was increased in GlPN (74%) vs PN (46%), P=0.03 (log-rank), as on D+100 (P=0.05). Most deaths occurred before D+100, especially in PN (10/26, 39%) vs GlPN (4/27, 15%). GVHD was the most frequent cause of death (8/21, 38%), especially in PN (n=6, five before D+100). Other outcomes were not affected. IP was affected on admission, was not affected by glutamine enrichment, but consistently worsened throughout the study. Results showed that GlPN was efficacious in increasing short-term survival after Allo-SCT. Benefits of glutamine seem to be independent of mucosal protection, as IP was not affected by its use. A trend to a lower incidence of GVHD deaths may suggest an immunomodulatory role of glutamine.

Body composition and overweight of liver transplant recipients.

Background. Overweight is often used as a description after liver transplantation (LTx), but studies on body composition of patients submitted to LTx have only been devoted to early postoperative periods; there is little information regarding abdominal obesity after LTx. The aim of this study was to assess body composition, body mass index (BMI), and waist circumference and verify the prevalence and risk factors for excessive weight, obesity, and abdominal obesity in long-term survivors of LTx. Methods. Post-LTx patients with at least 1 year post-LTx were assessed for their body composition (by bioimpedance), BMI, and waist circumference. Demographic, socioeconomic, lifestyle, and clinical and dietetic variables were collected to assess risk factors using linear and logistic regression analyses. Results. We evaluated 143 patients (51±13 years; 59.4% male; median time since LTx: 4 years). The majority of patients had excessive weight, considering BMI, (58.1%). Considering body composition, 69.9% of patients were overweight and 37.8% obese. Some degree of abdominal obesity was seen in 88% of patients. Independent risk factors for overweight, obesity, and abdominal obesity after LTx included greater BMI before liver disease, weight gain since LTx, family history of overweight, smoking, working, being married, having less time since transplantation, a lower calcium intake, and less sleeping hours. Conclusions. The majority of patients are overweight or obese after LTx, and many of the associated risk factors are modifiable. Thus, patients, especially those who already have identified risk factors for overweight and obesity, undergoing LTx should be encouraged to engage in lifestyle changes early.

Tuberculosis in liver transplant recipients: a single Brazilian center experience.

Background. Tuberculosis (TB) is an important opportunistic infection in transplant recipients worldwide. The frequency of Mycobacterium tuberculosis disease varies among different regions, but the incidence of TB in adult liver transplant (LT) recipients is largely unknown. The estimated frequency ranges from 0.7% to 2.3%, with mortality rate up to 30%. However, these data are based on individual case reports or series with small samples. In LT recipients, therapy is generally associated with significant hepatotoxicity and interactions with immunosuppressive drugs. Methods. This retrospective analysis included 319 patients who underwent LT at University Hospital, Federal University of Minas Gerais, Brazil, between September 1994 and July 2007 and survived more than 1 month. Among these, TB was diagnosed in five patients. No patients received chemoprophylaxis before or after LT. Results. All five patients were women, mean age 39.6±16.5 years. Two patients had disseminated TB, two pulmonary involvement, and one extrapulmonary disease. Cultures were positive in four patients. Overall, four patients received isoniazid, rifampin, and pyrazinamide for 6 to 12 months, with good tolerance, but one patient presented recurrence. Another patient presented raised hepatic enzymes levels after initiating therapy. All patients are alive and well. Conclusions. In this series, the TB frequency after liver transplantation was 1.57%, with no confirmed hepatotoxicity with conventional treatment and an excellent survival rate (100%).

Beneficial Effect of Synbiotic Supplementation on Hepatic Steatosis and Anthropometric Parameters, But Not on Gut Permeability in a Population with Nonalcoholic Steatohepatitis

Nonalcoholic fatty liver disease is the most prevalent chronic liver disease in Western countries; it can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocarcinoma. The importance of gut-liver-adipose tissue axis has become evident and treatments targeting gut microbiota may improve inflammatory and metabolic parameters in NASH patients. In a randomized, controlled clinical trial, involving 50 biopsy-proven NASH patients, we investigated the effects of synbiotic supplementation on metabolic parameters, hepatic steatosis, intestinal permeability, small intestinal bacterial overgrowth (SIBO) and lipopolysaccharide (LPS) serum levels. Patients were separated into two groups receiving Lactobacillus reuteri with guar gum and inulin for three months and healthy balanced nutritional counseling versus nutritional counseling alone. Before and after the intervention we assessed steatosis by magnetic resonance imaging, intestinal permeability by lactulose/mannitol urinary excretion and SIBO by glucose breath testing. NASH patients presented high gut permeability, but low prevalence of SIBO. After the intervention, only the synbiotic group presented a reduction in steatosis, lost weight, diminished BMI and waist circumference measurement. Synbiotic did not improve intestinal permeability or LPS levels. We concluded that synbiotic supplementation associated with nutritional counseling seems superior to nutritional counseling alone for NASH treatment as it attenuates steatosis and may help to achieve weight loss.

Prospective evaluation of metabolic syndrome and its components among long‐term liver recipients

Survival after liver transplantation (LTx) has increased. Metabolic syndrome (MS) is widely reported in patients in the early years after LTx; few studies have researched this condition in relatively long‐term liver recipients. To describe, prospectively, the prevalence of MS, its components and its associated factors in relatively long‐term liver recipients.

Whipple's disease. Report of five cases with different clinical features

Whipples disease (WD) is a rare systemic disease of infectious etiology which involves the small intestine but can virtually affect any organ. We present here five cases (four males and one female) ranging in age from 20 to 59 years. All patients had intestinal involvement associated or not with clinical manifestations linked to this organ. Vegetation in the tricuspid valve was observed in one patient, suggesting endocarditis caused by Tropheryma whippelii, with disappearance of the echocardiographic alterations after treatment. In one of the male patients the initial clinical manifestation was serologically negative spondylitis, with no diarrhea occurring at any time during follow-up. Ocular involvement associated with intestinal malabsorption and significant weight loss were observed in one case. In the other two cases, diarrhea was the major clinical manifestation. All patients were diagnosed by histological examination of the jejunal mucosa and, when indicated, of extraintestinal tissues by light and electron microscopy. After antibiotic treatment, full remission of symptoms occurred in all cases. A control examination of the intestinal mucosa performed after twelve months of treatment with sulfamethoxazole-trimethoprim revealed the disappearance of T. whippelii in four patients. The remaining patient was lost to follow-up.