European guidelines on microscopic colitis: United European Gastroenterology and European Microscopic Colitis Group statements and recommendations

Introduction: Microscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, nonbloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic colitis and the incomplete microscopic colitis. With ongoing uncertainties and new developments in the clinical management of microscopic colitis, there is a need for evidence-based guidelines to improve the medical care of patients suffering from this disorder. Methods: Guidelines were developed by members from the European Microscopic Colitis Group and United European Gastroenterology in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists, pathologists and basic scientists, and voted upon using the Delphi method. Results: These guidelines provide information on epidemiology and risk factors of microscopic colitis, as well as evidence-based statements and recommendations on diagnostic criteria and treatment options, including oral budesonide, bile acid binders, immunomodulators and biologics. Recommendations on the clinical management of microscopic colitis are provided based on evidence, expert opinion and best clinical practice. Conclusion: These guidelines may support clinicians worldwide to improve the clinical management of patients with microscopic colitis

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Effect of infliximab on small bowel stenoses in patients with Crohn's disease

AIM: To assess prospectively small bowel stenoses in Crohn's disease (CD) patients treated with infliximab using Small Intestine Contrast Ultrasonography (SICUS). METHODS: Twenty patients (M 12, age, 42.7 +/- 11.8 years), 15 of whom showed obstructive symptoms indicating the presence of small bowel stenosis, and 5 without stenosis, were treated with infliximab (5 mg/kg at A 0, 2, 6 and 5 mg/kg every 8 A thereafter) for steroid refractoriness, fistulizing disease, or to avoid high-risk surgery. SICUS was performed at the induction phase and at regular time intervals during the follow-up period of 34.7 +/- 16.1 mo (range 7-58). Small bowel stenoses were detected by SICUS, endoscopy and MRI. RESULTS: In no case was progression of stenoses or the appearance of new ones seen. Of the 15 patients with stenosis, 5 stopped treatment after the induction phase (2 for no response, 3 for drug intolerance, one of whom showed complete regression of one stenosis). Among the remaining 10 patients, a complete regression of 8 stenoses (1 stenosis in 5 patients and 3 stenoses in one patient) was observed after 6-22 infliximab infusions. CONCLUSION: In patients with CD treated with infliximab we observed: (a) No progression of small bowel stenosis and no appearance of new ones, (b) Complete regression of 1/22 stenosis after the induction phase and of 8/15 (53.3%) stenosis after 6-22 infusions during maintenance therapy. (c) 2008 WJG. All rights reserved

[The efficacy of slow-release diltiazem in the treatment of stable angina of effort: a comparison between diltiazem and placebo].

The efficacy of a new slow release (SR) diltiazem preparation was assessed in 10 patients with stable effort angina. A double-blind, placebo controlled, randomized, crossover protocol was carried out comparing the effects of diltiazem 60 mg tid and diltiazem SR 120 mg bid on clinical and ergometric parameters. Exercise test was carried out 3 and 12 hours after the last dose of diltiazem or diltiazem SR respectively. Both drug preparations reduced the incidence of positive test, increased the exercise time and the time of onset of ischemic ST depression. The beneficial effects of the drugs appeared to be due to a reduction in myocardial oxygen consumption at the same workload as shown by the lesser value of pressure rate product at submaximal exercise. In conclusion, diltiazem SR at 12 hours after the last administration has the same effectiveness of diltiazem 60 mg at 3 hours

Acute intestinal obstruction and NOD2/CARD15 mutations among italian Crohn's disease patients

Three CARD15 mutations (SNP8, SNP12, SNP13) were significantly associated with CD, however ethnic variations and genotype-phenotype relationships are still to be defined. Aims: To evaluate the prevalence of three CARD15 mutations in 91 in-out consecutive CD, 109 Ulcerative Colitis (UC), 101 healthy controls; to examine the genotype-phenotype relationships among italian pts with CD. Material and Methods: The three mutations were determined by direct sequencing analysis. In CD were evaluated several feature of disease phenotype. Data analysis was performed by using c2 or Fisher Test applying Bonferroni's correction. Results: The allelic and genotype frequencies of CARD15 mutations were significantly associated to CD. None of controls or UC were homozygotes (OM) or compound heterozigotes (CET). In CD the carriers of at least one mutation were 26/91 (28.6%). The frequencies of simple heterozygotes (ET), CET and OM were: 19/26, 4/26, 3/26 respectively. A significant positive association was found between small bowel location and an acute intestinal obstruction at diagnosis and the carriers of at least one mutation (p = 0.036, OR:0.33 [0.12-0.9] and p = 0.0025, OR:0.125 [0.03-0.5], respectively), particularly with OM and CET genotype (p = 0.005, OR:0.07 [0.01-0.6]). A positive trend between the number of surgery and the carriers of at least one mutation was found, but it didn't reach statistical significance (p = 0.0469, OR:0.3 [0.1-0.96]). No relationship between CARD15 mutations and the other phenotype characteristics was found. Conclusions: Our data confirms that CARD15 mutations are significantly associated with CD also in Italian population and with small bowel location (OM and CET genotype). A new positive association was also found between the carriers of at least one mutation and the acute intestinal obstruction at diagnosis