Classification of intestinal lymphangiectasia with protein-losing enteropathy: white villi type and non-white villi type.

BACKGROUND/AIMS: We classified intestinal lymphangiectasia (IL) into two categories, the white and non-white villi types, and evaluated their clinical characteristics and therapeutic responses. METHODS: Of the 988 patients who underwent double-balloon enteroscopy, 14 consecutive patients (7 men and 7 women, median age at onset 34 years) were enrolled with immunohistochemically confirmed IL with protein-losing enteropathy. RESULTS: Enteroscopically the white villi type (n = 8) showed white plaques and white-tipped villi were scattered in the small bowel, while non-white villi type (n = 6) showed that apparently normal but under more detailed observation, low and round villi with a normal color were diffused. The serum albumin levels and fecal α1-antitrypsin clearance before treatment were significantly worse in the non-white villi type (p = 0.017 and 0.039, respectively), whereas the serum immunoglobulin A and M levels were significantly lower in the white villi type (p = 0.010 and 0.046, respectively). At gastroscopy, a non-cirrhotic snakeskin appearance was significantly observed in the non-white villi type (p = 0.015). The corticosteroid response was better in the non-white villi type (p = 0.015). CONCLUSION: Two distinct subgroups were found in IL. This classification was useful in pathophysiological clustering and in predicting the therapeutic response.

TNF-alpha modulates iNOS expression in an experimental rat model of indomethacin-induced jejunoileitis.

Multiple mucosal immune factors, such as TNF-alpha and IL-1beta, are thought to be key mediators involved in inflammatory bowel disease. We evaluated the role of the pro-inflammatory cytokine TNF-alpha on nitric oxide synthase (NOS) expression in indomethacin-induced jejunoileitis in rats. Jejunoileitis was induced in rats with subcutaneous injections of indomethacin (7.5 mg/kg) 24 h apart for two consecutive days, and animals were randomized into four groups. Group 1 received only indomethacin. Group 2 was treated with a daily dose of phosphodiesterase (PDE) inhibitor (theophylline or pentoxifylline) by oral gavage for 2 days before and 4 days after indomethacin. Group 3 received a single dose of anti-TNF-alpha monoclonal antibody (TNF-Ab, IP) 30 min before indomethacin. Group 4 was treated with 1 h hyperbaric oxygenation (HBO(2)) for 5 days after indomethacin. Rats were sacrificed at 12 h or 4 days after final indomethacin injection. PDE inhibitor, TNF-Ab, or HBO(2) treatment significantly decreased indomethacin-induced ulceration, myeloperoxidase activity, and disease activity index. Although indomethacin significantly increased serum TNF-alpha and nitrate/nitrite (NOx) concentrations above control values at 12 h, inducible NOS (iNOS) expression was detected only at day 4. Serum IL-1beta levels did not change at 12 h but increased 4-fold after 4 days. Indomethacin had no effect on constitutive NOS. Treatment with PDE inhibitor, TNF-Ab, or HBO(2) significantly reduced serum/tissue TNF-alpha, IL-1beta, NOx, and iNOS expression. Our data show TNF-alpha plays an early pro-inflammatory role in indomethacin-induced jejunoileitis. Additionally, down-regulation of NOx by PDE inhibitors, TNF-Ab, or HBO(2) suggests that TNF-alpha modulates iNOS expression.

Diamine oxidase, a plasma biomarker in rats to GI tract toxicity of oral fluorouracil anti-cancer drugs.

Diamine oxidase (DAO; EC 1.4.3.6), which catabolizes a variety of substrates including histamine and diamines, is the degradative enzyme of the catabolic pathway of polyamines found in high activity in the mature upper villus cells of the rat intestinal mucosa [Luk, G.D., Bayless, T.M., Baylin, S.B., 1983. Plasma post-heparin diamine oxidase. Sensitive provocative test for quantitating length of acute intestinal mucosal injury in the rat. J. Clin. Invest. 71, 1308-1315; Wolvekamp, M.C.J., de Bruin, R.W.F., 1994. Diamine oxidase: an overview of historical, biochemical and functional aspects. Dig. Dis. 12, 2-14]. Rats were given 1-week repeated oral administration of anti-cancer drugs S-1, containing FT+CDHP+Oxo, and FCD, containing FT+CDHP, and the ameliorating effect of Oxo on the rat gastrointestinal (GI) tract toxicity from 5-FU was evaluated by measuring plasma DAO activity which is related to the enzyme located in the rat intestinal mucosa. Plasma DAO activity in the FCD-treated group was significantly less than that in the S-1-treated group while the jejunal mucosal area in the FCD group was significantly smaller than that in the S-1 group. In addition the histopathological findings in the FCD group showed villus atrophy in the jejunal mucosa which was not observed in the S-1 group. The degree of these findings correlated with the plasma DAO levels. Therefore, the protective effect of Oxo on 5-FU-induced GI tract toxicity was clarified by measuring plasma DAO activity in rats. In summary, DAO is a very sensitive plasma biomarker and will be useful for the quantitative evaluation of the small intestinal mucosal lesions induced by the anti-cancer drug, 5-FU, in rats.

Acute self-limiting jejunitis as the first manifestation of microscopic polyangiitis associated with Sjogren's disease: report of one case and review of the literature.

We report a case of acute self-limiting ulcerative jejunitis of unknown aetiology in a 72-year-old female patient in which a subsequent diagnosis of microscopic polyangiitis and Sjogren's syndrome was made. All known causes of jejunal ulceration and inflammation were excluded. Previously reported cases of acute self-limiting jejunitis are reviewed and the possibility that acute jejunitis in this patient had been the first manifestation of systemic vasculitis is discussed.

Normal T-helper 1/T-helper 2 balance in peripheral blood of coeliac disease patients.

Activated T cells, with their secretion of cytokines, probably play an important role in the pathogenesis of mucosal lesions in coeliac disease (COD) and the prominence of a T-helper (Th)1-type cytokine pattern has been reported. As the process of immunological activation in the jejunal mucosa in active CoD has been shown to also cause some differences in peripheral blood lymphocyte populations, we sought to establish any changes in the Th 1/Th2 balance in peripheral blood of patients, at different stages of CoD, relative to healthy individuals. Twenty-two CoD patients and 10 healthy controls were included in the study. The Th1/Th2 balance was examined both in resting cells and after polyclonal stimulation using two different methods: intracytoplasmic cytokine contents were measured using an intracellular staining method and three-colour flow cytometry and cytokine contents of cell culture supernatants were measured using traditional enzyme-linked immunosorbent assays (ELISAs). Interferon-gamma (IFN-gamma)-producing cells (Thl) were as prominent in untreated CoD patients and treated CoD patients as in healthy controls, while cells fitting a Th2 or ThO-type cytokine pattern were few in all groups. In ELISA assays, Th1 type (IFN-gamma or interleukin (IL)-2) cytokines were again prominent in all study groups but no statistically significant differences were found in IFN-gamma, IL-4 or IL-2 levels among the three groups. These results suggest that the increased shift towards a Th1 response is mainly restricted to the actual site of inflammation and that circulating T cells do not show a similar response, presumably because activated cells in peripheral blood are too few. Further research on cytokine profiles measuring T-cell activation in CoD should be focused on the actual tissue of inflammation.

Ulcerative jejunitis: are we missing cases?

We present two cases of ulcerative jejunitis unassociated with coeliac disease. The condition is probably being underdiagnosed especially since the reduction in the investigative laparotomy.

[Ultrastructural changes in neutrophils and anaerobic microorganisms during their interactions in experimental acute intestinal obstruction]. / Ul'trastrukturnye izmeneniia neitrofil'nykh granulotsitov i anaérobnykh mikroorganizmov pri ikh vzaimodeistvii v usloviiakh éksperimental'noi ostroi neprokhodimosti kishechnika.

The authors established that 12 h after development of acute obstructive ileus in inactive neutrophil granulocytes (NG), the anaerobic microorganisms were intact, or at the process of division; in the active NG, they were destroyed, or when forming "halo", might preserve and migrate in the matrix of NG. In interaction of NG with microorganisms, the numerous oval and roundish bacterial bodies with a diameter of 0.2-0.5 micron capable to penetrate into the non-phagocytic cells are formed. A function of the formations revealed is not studied.

Changes of plasma amino acids in total parenteral nutrition-supported patients with intraabdominal infection.

Plasma aminogram changes were prospectively studied in 95 patients with external enteric fistula and intraabdominal infection who were under total parenteral nutrition (TPN) therapy with anfuming 14s. Plasma amino acids and albumin were determined before the administration of TPN, weekly and at the end of the therapy or 2 to 5 days before death of patients. In patients with sepsis and starvation, the aminogram showed remarkably low total free amino acids before TPN therapy. In survivors, free amino acids increased gradually to normal in 2 weeks after use of TPN and in the dead increased rapidly to a significantly high peak at the terminal stage. In both survivors and deceased, phenylalanine level remained high during the study. In response to infection, proline was also elevated but to a lesser degree; the ratio of branched chain amino acid (BCAA) to aromatic amino acid (AAA) was lower than normal and the decrease of arginine was parallel to the severity of infection. We conclude that the ideal amino acid preparation for the starved, septic patients should be high in BCAA and arginine but low in phenylalanine; the administration of inappropriate exogenous amino acids in metabolically decompensated septic patients may bring about more harm than benefit; and in septic patients the persistently elevated level of plasma phenylalanine and proline along with decrease of arginine is a useful prognostic sign.

Erythrocytic sedimentation rate as a measure of clinical activity in inflammatory bowel disease.

To assess the reliability of the erythrocytic sedimentation rate (ESR) as a measure of clinical activity in inflammatory bowel disease, we analyzed the correlations of ESR with a global assessment of clinical activity in 77 patients with varying extents of Crohn's disease and ulcerative colitis. Analysis of all 141 ESR determinations in all 77 patients showed a highly significant correlation between mean ESR and clinical activity score (r = 0.54, p less than 0.001). Analysis of 133 ESR determinations in these 77 patients when their disease activity was either mild, moderate, or severe showed some significant differences among certain disease categories. The highest mean ESRs were in patients with the most extensive colon involvement (Crohn's colitis 40.7 +/- 3.3, universal ulcerative colitis 31.0 +/- 3.9), whereas the lowest mean ESRs were in patients with the most limited disease (ulcerative proctitis and proctosigmoiditis 19.2 +/- 2.1). The rate of increase in ESR with progressively increasing clinical activity from mild to moderate was the same in all disease categories, with the exception of Crohn's disease limited to the small bowel (ileitis or jejunoileitis), in which the ESR was relatively unchanged in a small sample of patients. By the time clinical activity became severe, however, patients in all disease categories manifested similarly high ESRs, with the exception of ulcerative proctitis in which the ESR remained low in the single patient tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum pepsinogen I levels: assessment of gastric acid secretion?

We measured serum PG I levels by an Elisa technique before and after stimulation with pentagastrin in 260 patients (161 males and 99 females). The serum levels were correlated to basic acid output (BAO), maximum acid output (MAO) and peak acid output (PAO). The correlation coefficient between serum PG I and PAO varied between -0.482 and 0.744 depending on the diagnosis. This indicates that a simple measurement of PG I cannot replace the pentagastrin test in estimating gastric acid secreting capacity. However, since all patients who were achlorhydric had a serum PG I level of less than 50 micrograms/l the measurement of serum PG I can be recommended as a screening test for achlorhydria.

Endotoxemia following experimental intestinal strangulation obstruction in ponies.

Experimental small intestinal strangulation obstruction was produced in anesthetized ponies. The limulus amoebocyte lysate test demonstrated the presence of endotoxin in the general circulation 60 and 120 minutes following restoration of mesenteric blood flow. Mucosal degeneration, with loss of villus epithelial cells, was demonstrated coincident with endotoxemia. The findings were consistent with an ischemia-mediated alteration in the intestinal barrier to endotoxin.