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PubMed2005

Involvement of Th1 cells and heat shock protein 60 in the pathogenesis of intestinal Behcet's disease.

Involvement of excessive Th1 cell functions and heat shock protein expression in the pathogenesis of Behcet's disease (BD) has been reported. In this study we have characterized immune responses in intestinal lesions of BD. Peripheral blood lymphocytes (PBL) of BD and healthy controls (HC) and tissue specimens of intestinal Behcet's disease (intestinal BD), Crohn's disease (CD) and ulcerative colitis (UC) were analysed for mRNA and protein expression by reverse transcriptase-polymerase chain reaction (PCR) and immunohistochemistry, respectively. PBL of BD patients expressed the Th1-related chemokine receptor, CCR5 and CXCR3 preferentially compared with those of healthy controls. Intestinal lesions of BD expressed interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and interleukin (IL)-12 mRNA, indicating Th1 skewed responses in vivo. mRNA of Txk, a Tec family tyrosine kinase specific to Th1 cells, was expressed in the lesions, suggesting its contribution to the Th1-dominant responses. In the intestinal samples, CCR5 was detected in all the cases with BD, whereas Th2-related CCR3 and CCR4 were detected randomly, mainly in the cases with inactive BD and those receiving large amounts of prednisolone, indicating the Th1-dominant immune responses in the intestinal lesions. As the ligands of CCR5, MIP1alpha and MIP1beta were detected, whereas RANTES was not. Heat shock protein (HSP) 60 was expressed in PBL and intestinal tissues of BD. Th1-dominant immune responses and HSP60 expression may induce the inflammatory responses and thus be associated with the pathogenesis of intestinal BD.

Adult↗
PubMedDate not supplied

New trends in non-absorbable antibiotics in gastrointestinal disease.

Numerous antibiotics have been used for several years in the treatment of intestinal diseases, the majority belonging to the class of aminoglycosides. These are effective against gram-positive and some gram-negative bacteria, above all aerobes, and do not therefore cover the entire range of microorganisms responsible for intestinal infections. With these antibiotics, moreover, it is not possible to exclude intestinal absorption which can lead to serious side effects. Other intestinal antibiotics, however, such as Vancomycin, have a restricted spectrum of action which limits their use. This study analyzes the pharmacological characteristics of a new non-absorbable antibiotics with particularly interesting properties from a clinical pharmacokinetic and pharmacodynamic point of view: Rifaximin. This drug has an extremely broad spectrum of action covering all intestinal germs, and its absorption is practically zero. The results of some controlled clinical studies in gastrointestinal diseases are examined, such as the treatment of infectious diarrhoea, of acute or chronic portal-caval encephalopathy and of diverticular disease of the colon. The possible role of Rifaximin in some intestinal diseases, such as small bowel bacterial overgrowth and Crohn's disease and ulcerative colitis, is also analyzed.

Bacterial Infections↗
PubMed1976

Enterokinase and trypsin activities in pancreatic insufficiency and diseases of the small intestine.

The interrelationship of enterokinase and trypsin activities were investigated in 133 infants and children with a variety of gastrointestinal and pancreatic disorders. Fourteen patients with diarrhea and grade II mucosal injury revealed a significant (P less than 0.01) reduction of enterokinase, trypsin, and disaccharidase activites as compared to 59 children with normal mucosa. Nine patients with cystic fibrosis and pancreatic insufficiency had normal mucosal enterokinase activity and elevated intraluminal enterokinase activity with very low or no trypsin activity. Patients with hypoproteinemia and gastrointestinal protein loss, associated with intestinal lymphangiectasia (4 patients) and intestinal lymphoid nodular hyperplasia (3 patients), had normal or insignificant decrease of enterokinase and trypsin activities. In patients with steatorrhea, a normal sweat test, normal intestinal mucosa, and absent trypsin activity, two entities were defined. One group (3 patients) was diagnosed as Schwachman-Diamond syndrome with pancreatic insufficiency and normal mucosal and intraluminal enterokinase activity. The second group (2 patients) with absent mucosal and intraluminal enterokinase activity and normal lipase and amylase activities was diagnosed as congenital enterokinase deficiency.

Child↗
PubMed1989

[Diarrhea in intestinal inflammatory diseases].

Diarrhoea is a frequent symptom in ulcerative colitis (UC) and Crohn's disease (CD) which it often reveals. Its clinical features, course, physiopathology and treatment are different in these two diseases. UC is accompanied by an imperative, blood-stained, diurnal and often noctural diarrhoea the intensity of which fluctuates with the course of the disease, usually regressing under medical treatment but capable of becoming severe. This diarrhoea is due to several physiopathological mechanisms such as loss of colonic absorption function, exudative enteropathy and disorders of motility. Contrary to the lesions of UC, those of CD involve the whole digestive tract; they are multisegmental, ileal, colonic, ileocolonic or diffuse. Diarrhoea takes different forms depending on the site and evolutive stage of the lesions: malabsorption of bile salts and/or fatty acids in ileal lesions or after surgical resections, bacterial proliferation above stenoses, intestinal shunts due to internal fistulae, reduced absorbing area, exudative enteropathy and motor disorders in colonic lesions. In UC, treatment of the diarrhoea is that of exacerbations: systemic or topical corticosteroids or 5-aminosalicylic acid. In CD, side by side whit the maintenance treatment of the disease with anti-inflammatory drugs, the symptomatic treatments of diarrhoea play an important role and must be tailored to the responsible physiopathological mechanisms; some patients need artificial feeding.

Anti-Inflammatory Agents↗
PubMed2001

Success and failure after repair of rectovaginal fistula in Crohn's disease: analysis of prognostic factors.

OBJECTIVE: To compare the healing rate after several types of surgical repair of rectovaginal fistula (RVF) in Crohn's disease, and to identify factors predicting a successful outcome. PATIENTS AND METHODS: A Medline review of the literature since 1980 and analysis of our results in 32 consecutive patients was done. RESULTS: All types of repair (rectal, vaginal, anocutaneous advancement flap, or perineoproctotomy with fistula closure) seem to be equally effective. Healing after a first repair is observed in 58 (46-71)%. Healing can still be obtained at subsequent attempts in 62 (40-71)% of the patients. The reported overall healing rate is 75 (56-93)%. The need for proctectomy after an attempt to repair was 6 (0-27)% in these series. Using a tailored surgical approach, we observed primary healing in 57%, healing after one or more supplementary procedures in 71%, for a total 'definitive' closure rate of 75%. Anal continence was never compromised and all temporary stomas (12 patients) could be closed. Univariate analysis identified number of Crohn's sites, presence of extra-intestinal disease and previous Crohn's proctitis to be related with problematic healing after a surgical repair. A positive relation was found between extra-intestinal disease and the number of repairs needed to ultimately obtain healing, whereas the relation with previous right hemicolectomy was negative. Multivariate analysis revealed the number of Crohn's sites as the only factor predicting problematic healing. A defunctioning stoma was not related to the healing rate and had its intrinsic morbidity with supplementary hospitalization (9.6 days). After a median follow-up of 40.4 (range 8-87) months, we observed 4 late recurrences in 25 patients with healed RVF (16%). CONCLUSION: Closure of a RVF in Crohn's disease should not be considered an easy undertaking, especially in patients with several Crohn's sites. In this very heterogeneous group of patients the technique is adapted to the nature and the extent of accompanying anorectal disease. Construction of a temporary stoma is not mandatory and can be limited to complex cases. Healing can be obtained in 75% of all patients, although a late recurrence might occur.

Journal Article↗
PubMed2005

Celiac disease and intestinal metaplasia of the esophagus (Barrett's esophagus).

Previous studies on celiac patients demonstrated that exposure to gliadin alters the motility of the upper gastrointestinal tract, leading to increased acid reflux. No literature is available regarding the possible presence of specialized intestinal metaplasia of the esophagus as a consequence of chronic reflux in adult celiac patients. Our purpose was to evaluate endoscopically and histologically the esophagi of a group of untreated celiac patients. We studied 60 celiac patients, 13 men and 47 women (mean age, 40 +/- 14 [SD] years; range, 18-80 years), at their first endoscopy (following a normal diet). The distal esophagus was evaluated and multiple biopsies were taken. Hematoxylin-eosin and alcian blue stainings were performed. A group of nonceliac, age- and sex-matched patients was used as a control. We found intestinal metaplasia in the distal esophagus of 16 of 60 (26.6%) celiacs (mean age, 45 +/- 13 years; range, 27-75 years), in comparison with a control-group prevalence of 10.9% (OR, 3.9; 95% CI, 1.4-11.2%). Among the celiac group with metaplasia, only one patient had reflux-like symptoms. None had esophagitis. In conclusion, we observed an increased prevalence of esophageal metaplasia in patients with celiac disease. This finding could be the result of motor abnormalities leading to chronic acid reflux, combined with a mucosa which is sensitive to gliadin.

Adult↗
PubMed2005

Notch and Wnt inhibitors as potential new drugs for intestinal neoplastic disease.

Colorectal cancer is a major cause of death in the western world. Recent advances in treatment comprise variations on the classical themes of surgical resection combined with chemotherapy using cytotoxic drugs and radiation therapy. Because this therapy is only moderately successful, novel approaches to the treatment of colorectal cancer are required. Our rapidly increasing knowledge of molecular signalling pathways that are deregulated in colorectal cancer might provide a platform from which to develop new rational cancer therapies. Here, we give an update on the roles of the Wnt and Notch signalling pathways in the self renewal of the intestinal epithelium and the consequences of Wnt deregulation in colorectal cancer. We focus on the potential of recently identified small-molecule inhibitors of the Wnt pathway and gamma-secretase inhibitors of the Notch pathway as novel colon cancer therapeutics.

Amyloid Precursor Protein Secretases↗
PubMed1992

[Evaluation of the immunoenzyme test (Elisa) in detecting Clostiridium difficile toxin A in fecal samples].

Currently, the method of choice in diagnosis of Clostridium difficile-associated intestinal diseases is the detection of toxin B in fecal specimens. This method is long (72 h) and can be realized in laboratories which have tissue culture facilities. Commercial agglutination test have been evaluated but they lack in specificity. An immunoenzymatic test has been recently commercialized for detection of toxin A. We have compared the results of this assay on 275 fecal specimens from patients suspected of having Clostridium difficile-associated intestinal diseases with the results obtained with the cytotoxicity test and the culture. Of the 275 fecal specimens, 58 were positive in cytotoxicity and 53 in Elisa. The overall sensitivity and specificity of the Elisa compared with cytotoxicity were 89.5% and 99.0% respectively. The immunoenzymatic test detecting Clostridium difficile toxin A is an easy test to perform in 2 h 15; it displays a good correlation with detection of toxin B and can be very useful in daily laboratory diagnosis.

Bacterial Toxins↗
PubMed1987

Salivary immunoglobulins in healthy white and black adults compared with oesophageal cancer patients.

Saliva is a readily accessible mucosal secretion and salivary antibodies reflect the repertoire of gut-associated antigens; it therefore appears to be ideal for the study of gastro-intestinal disease. A study of salivary immunoglobulins in healthy white and black adults and patients with oesophageal cancer showed that salivary immunoglobulin A levels were higher (but not significantly) in whites than blacks. The levels, however, were similar in healthy blacks and oesophageal cancer patients. There is a wide variation in normal levels of salivary immunoglobulins. Also, immunoglobulins are readily influenced by physiological factors and so at present are unreliable indices of gastro-intestinal disease.

Adult↗
PubMed1999

Clostridium difficile: an update on its epidemiology and role in hospital outbreaks in England and Wales.

Data from the surveillance system of general outbreaks of infectious intestinal disease and from laboratory reports collated by the Communicable Disease Surveillance Centre (CDSC) and requests for outbreak investigation by the PHLS Anaerobe Reference Unit were used to evaluate the current epidemiology of Clostridium difficile infection in England and Wales. Between January 1992 and December 1996, CDSC received 10,220 laboratory reports of C difficile isolation from patient's faeces and 26,873 of toxin in faeces. Over 75% of all reports were of people aged 64 years and over. The surveillance system captured a minimum data set on 694 hospital outbreaks of infectious intestinal disease. C. difficile was responsible for 109 (15%) outbreaks affecting 1625 people, of whom 1152 were found to have a C. difficile toxin producing strain. The median duration of outbreaks was 11 days. Fingerprinting by Pyrolysis Mass Spectrometry (PMS) was performed by the PHLS Anaerobe Reference Unit in 60 outbreaks, and typing by Polymerase Chain Reaction ribotyping (PCR) in 14.

Adolescent↗
PubMed1980

Fecal intestinal alkaline phosphatase in coeliac disease.

The intestinal alkaline phosphatase (I-AP) in feces was investigated in 16 patients with adult coeliac disease and 2 patients with gluten-sensitive enteropathy in dermatitis herpetiformis using an immunoprecipitation method. The mean concentration of I-AP activity in feces was reduced by 76% in patients with coeliac disease in comparison to normal controls (11.5 : 47.5 U/g). Patients with total villous atrophy (mean = 5.3 U/g) demonstrated a lower activity than patients with partial villous atrophy (mean = 14.3 U/g). Follow-up studies showed stable fecal I-AP-activities in symptom-free patients, whereas patients with relapses were characterized by fluctuating activities. The administration of a single oral dose of 31 g gluten is followed by a fecal I-AP-excretion pattern similar to toxic damage of the small bowel mucosa.

Alkaline Phosphatase↗
PubMedDate not supplied

[Morphological, clinical and therapeutic characteristics of Cyclospora cayetanensis].

In the last years Cyclospora sp. has been increasingly associated to human intestinal diseases. The first studies have been reported to this parasite as a Cyanobacterium-like body, large Cryptosporidium or coccidian-like body. The ultrastructural characteristic and the "in vitro" sporulation have revealed the existence of oocyst constituted for two sporocysts with two sporozoites per sporocyst. This evidence has allowed its classification as a coccidian within the genus Cyclospora and its designation as a new pathogen species in humans, Cyclospora cayetanensis. Recently phylogenetic analysis based on rDNA sequences suggested that Cyclospora sp. was closely related to the Eimeria genus. The identification, morphological characteristics, clinical evaluation and chemotherapy of the human intestinal disease associated to Cyclospora sp. are commented in the present paper.

Animals↗