Prehepatic portal hypertension produces increased mast cell density in the small bowel and in mesenteric lymph nodes in the rat

BACKGROUND: Because most of the characteristics of the portal hypertensive enteropathy can be explained on the basis of increased levels of mast cell mediators, the purpose of the present paper was to study mast cell splanchnic infiltration. METHODS: Duodenum, jejunum, ileum and mesenteric lymph node complex infiltration by mast cells was assayed by a stereological technique in control rats (group I; n = 5) and in an experimental model of portal hypertension (the portal vein-stenosed rat, group II; n = 5) at 6 weeks after operation. RESULTS: Intestinal and mesenteric lymph node complex infiltration by mast cells increased in the animals with partial portal vein ligation. The mast cell density progressively increased distally along the small bowel. The mast cell increase in the mesenteric lymph node complex in portal vein-stenosed rats was greater than in the duodenum (P = 0.001), jejunum (P = 0.006) and ileum. CONCLUSION: The rise of mast cells density in the small bowel and mesenteric lymph node complex in rats with partial portal vein ligation suggests that these cells are involved in the etiopathogenesis of experimental portal prehepatic hypertensive enteropathy.     

Selective expansion of donor‐derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome

IPEX syndrome is a rare and fatal disorder caused by absence of regulatory T cells (Tregs) due to congenital mutations in the Forkhead box protein 3 gene. Here, we report a patient with IPEX syndrome treated with RIC followed by allogeneic BMT from an HLA‐matched sibling donor. We could achieve engraftment and regimen‐related toxicity was well tolerated. Although the patient was in mixed chimera and the ratio of donor cells in whole peripheral blood remained relatively low, selective and sustained expansion of Tregs determined as CD4+CD25+Foxp3+ cells was observed. Improvement in clinical symptoms was correlated with expansion of donor‐derived Tregs and disappearance of anti‐villin autoantibody, which was involved in the pathogenesis of gastrointestinal symptoms in IPEX syndrome. This clinical observation suggests that donor‐derived Tregs have selective growth advantage in patients with IPEX syndrome even in mixed chimera after allogeneic BMT and contribute to the control of clinical symptoms caused by the defect of Tregs.     

Low-dose aspirin-induced gastrointestinal diseases: past,present, and future

Meta-analyses of randomized, placebo-controlled trials of low-dose aspirin indicate that aspirin approximately doubles the risk of major GI bleeding compared with placebo. The risk in Japanese may possibly be higher compared to Western populations, although the evidence is still lacking and prospective studies are required. Prior GI events, older age, and use of other injurious medicines such as NSAIDs, anticoagulants, and corticosteroids seem to be factors associated with an increased risk for upper GI bleeding among aspirin users. Prospective studies are needed to identify specific risk factors for upper GI bleeding in Japanese patients taking low-dose aspirin. There are many potential gastroprotective drugs available in Japan, and studies are needed to assess the relative effectiveness of various strategies including PPI use for the prevention of aspirin-related upper GI ulcer complications and whether any of these other agents also provide protection against small bowel or colonic damage. Aspirin-induced enteropathy is now increasingly being recognized and is presumably not uncommon, and the availability of new imaging techniques for the small intestine and noninvasive tests such as fecal calprotectin should allow rapid progress in this important area.     

Decreased prevalence of celiac disease among Brazilian elderly

AIM: To evaluate the prevalence of celiac disease in a group of Brazilian individuals over 60 years of age and compare it with the previously known prevalence in a pediatric group living in the same geographical area.METHODS: The research protocol was approved by the Ethics Committee of the University of Brasilia School of Medicine, Brasilia, Brazil. Blood samples from 946 individuals (295 male and 651 female) aged 60 years or older were collected between May 2010 and July 2011. The study subjects’ mean and median ages were 68.1 and 67 years, respectively, ranging from 60 to 92 years. That age distribution closely corresponded to the age distribution of the Brazilian population according to the Brazilian 2010 census. The participants were consecutive and unselected outpatients undergoing blood tests at the University of Brasilia Hospital’s Clinical Pathology Laboratory. All sera were tested for immunoglobulin A anti-transglutaminase antibodies (IgA-tTG) by enzymelinked immunosorbent assay, and those that were positive were further tested for immunoglobulin A antiendomysium antibodies (IgA-EMA). Human leukocyte antigen (HLA) genotyping was performed for all individuals who exhibited positive serologic results for IgA-tTG and/or IgA-EMA.RESULTS: Out of the 946 studied patients, only one previously diagnosed case of biopsy-proven celiac disease was detected. For the remaining subjects, nine serum samples tested positive for IgA-tTG antibodies; however, none of them tested positive for IgA-EMA antibodies. The HLA genotyping of those nine subjects revealed that one was carrying DQA1*0501 and two were carrying DQB1*0201 alleles. These data showed that, among those 946 elderly individuals, the prevalence of celiac disease (CD) was 0.1% (95%CI: 0.00-0.59). The prevalence of CD for the elderly group was compared with that observed for the group of 2034 children younger than 15 years (age range, 1-14 years; mean age, 8 years) who took part in our previous CD prevalence screening study. All the children came from the s     

Idiopathic Bile Acid Diarrhoea Reconsidered

Two new cases of a rare entity provisionally coined ‘idiopathic bile acid diarrhoea’ are reported and compared with previous cases. The diarrhoeal syndrome has been identified as a cholegenic enteropathy. In the absence of conventional ileopathy the cause of the bile acid loss is obscure, but it is hypothesized that it may be due to a relative deficiency in ileal absorptive sites for bile acid anions. So far the diagnosis has partly been based on measurements of faecal bile acid losses. It is suggested that a carefully conducted therapeutic trial with cholestyramine may be almost equally helpful.     

Octreotide in Hennekam syndrome-associated intestinal lymphangiectasia

A number of disorders have been described to cause protein losing enteropathy (PLE) in children. Primary intestinal lymphangiectasia (PIL) is one mechanism leading to PLE. Few syndromes are associated with PIL; Hennekam syndrome (HS) is one of them. The principal treatment for PIL is a high protein, low fat diet with medium chain triglycerides supplementation. Supportive therapy includes albumin infusion. Few publications have supported the use of octreotide to diminish protein loss and minimize hypoalbuminemia seen in PIL. There are no publications on the treatment of PIL with octreotide in patients with HS. We report two children with HS and PLE in which we used octreotide to decrease intestinal protein loss. In one patient, octreotide increased serum albumin to an acceptable level without further need for albumin infusions. The other patient responded more dramatically with near normal serum albumin levels and cessation of albumin infusions. In achieving a good response to octreotide in both patients, we add to the publications supporting the use of octreotide in PIL and suggest that octreotide should be tried in patients with PIL secondary to HS. To the best of our knowledge, this is the first case report on the use of octreotide in HS-associated PIL.     

The interactive role of mucosal T lymphocytes in intestinal growth, development and enteropathy

Abstract Over the past 15–20 years, research has progressively focused on the mucosal T cell as the central factor in the initiation of physiological or pathological changes, first in the growth and maturation of the early (postnatal) intestine, and second in adult-type enteropathies resulting from sensitivity to either food or pathogen-derived antigens. T cell-mediated events may be measured, for example, in terms of specific immunopathologic patterns of change and injury, such as type 1 (lymphocyte infiltration), type 2 (crypt hyperplasia) and type 3 (flat-destructive), which can be recognized and quantitated microscopically; by determination of lymphocyte reactivity through secretion of interleukin-2 receptors (IL-2R) into plasma or expression by mucosal lymphocytes; by quantitation of lymphocyte subsets emigrating into inflamed tissues by immunoperoxidase-labelled monoclonal antibodies; or by the determination of T cell receptor polymorphisms. Alterations in intestinal growth, structure and function at weaning are likely to be T cell-mediated as they are analogous to the same type 1/2 lesions that reflect modulation of adult mucosal architecture in food and parasite-induced hypersensitivity reactions. Enteropathies associated with HIV infection and T cell deficiency display a milder degree of villous flattening and impaired crypt hyperplasia than that typical of gluten-sensitivity, suggesting a reversion to lesser degrees of mucosal pathology (type 1/2). Clearly more information will accrue; meanwhile the remarks in this brief survey should provide a firm basis whereby clinician and scientist can meet, and together recognize and further dissect the modulatory effect of T lymphocytes on mucosal structure and function.     

Results of transcatheter Fontan fenestration to treat protein losing enteropathy.

Transcatheter fenestration to create an interatrial communication has been used to treat patients with protein losing enteropathy (PLE) after Fontan operation. No systematic data have been reported assessing the results of this procedure. Our institutional database was queried to identify patients after Fontan operation who had transcatheter fenestration to treat PLE. Clinical notes, laboratory data, echocardiograms, and cardiac catheterization data were reviewed. From 1995 to 2005, 16 transcatheter fenestration procedures were performed in seven patients. Median age at fenestration was 18 years (range 13-41 years). Median duration of follow-up was 3.6 years (range 0.2-10.4 years). Techniques for fenestration included blade/balloon septostomy, stent placement, Amplatzer-fenestrated ASD device, and balloon dilation of previous stent. Size of the fenestration created was 5.2 +/- 1.1 mm. Systemic venous pressure remained unchanged after fenestration. Cardiac index increased significantly. Reduction of ascites and edema was noted after 9 of the 16 procedures. Ten of 16 (63%) of fenestrations spontaneously occluded. Three patients are free of ascites although recurrence of PLE occurred in all. One patient with a patent fenestration continues to have ascites. Two patients had Fontan takedown. One patient had conversion to a fenestrated extracardiac conduit Fontan and died postoperatively. The results of transcatheter Fontan fenestration are often disappointing. Maintaining fenestration patency is difficult. Even after "successful" fenestration, resolution of PLE may be incomplete and recurrences have occurred in all. Early consideration should be given to Fontan takedown or cardiac transplant in severely symptomatic patients with PLE who do not respond to fenestration. Transcatheter fenestration may be a bridge to a definitive procedure.     

Selective inhibition of COX-2 in humans is associated with less gastrointestinal injury: a comparison of nimesulide and naproxen

BACKGROUND: Selective inhibitors of cyclooxygenase (COX)-2 may provoke less gastric damage and platelet inhibition than conventional non-steroidal anti-inflammatory drugs. AIMS: We compared the biochemical and gastrointestinal effects of nimesulide, a potent and selective COX-2 inhibitor, with naproxen which exhibits no selectivity. SUBJECTS: Thirty six healthy volunteers were randomised to nimesulide 100 mg or naproxen 500 mg twice daily for two weeks in a double blind, crossover study with a washout between treatments. METHODS: Gastrointestinal side effects were assessed by endoscopy, and by estimation of small intestinal absorption-permeability and inflammation. Comparisons were made between variables at the end of each treatment phase. RESULTS: Nimesulide caused significantly less gastric injury using the modified Lanza score (p<0.001) as well as reduced duodenum injury (p=0.039). Nimesulide had lower visual analogue scores (VAS) for haemorrhage and erosive lesions in the stomach (p<0.001) and for mucosal injection in the duodenum (p=0.039). Naproxen increased excretion of calprotectin, a marker of intestinal inflammation (5.5 (1.2) to 12.1 (2.1) mg/l) while nimesulide had no effect (treatment difference p=0.03). Naproxen abolished platelet aggregation to arachidonic acid and suppressed serum thromboxane B(2) (TXB(2)) by 98%, indices of COX-1 activity. In contrast, nimesulide had no significant effect on platelet aggregation, although it reduced serum TXB(2) by 29%. Production of prostaglandin E(2) and prostacyclin by gastric biopsies, also COX-1 dependent, was inhibited by naproxen, but not by nimesulide. COX-2 activity, determined as endotoxin induced prostaglandin E(2) formation in plasma, was markedly suppressed by both treatments. INTERPRETATION: Nimesulide has preferential selectivity for COX-2 over COX-1 in vivo at full therapeutic doses and induces less gastrointestinal damage than that seen with naproxen in the short term.