Objective. Iron deficiency and anemia are being increasingly recognized as a complication of inflammatory bowel disease (IBD). The aim of this study was to observe, in a non-interventional way, how Swedish gastroenterologists adhere to guidelines in IBD outpatients treated with intravenous ferric carboxymaltose (FCM), and the result of treatment. Material and methods. Altogether 394 IBD patients (Crohn's disease (CD) 60%, ulcerative colitis (UC) 40%) from 14 centers were included. Group A (n = 216) was observed from November 2008 and group B (n = 178) from March 2010. Time of observation ranged from 12 to 29 months. Results. S-Ferritin (mmol/l) and transferrin saturation (T-Sat; %) were recorded at baseline in 62% and 50% in group A. Median values for Hb, ferritin and T-Sat at baseline were 111 g/l, 10 mu mol/l and 10%, respectively, and 134 g/l, 121 mmol/l and 20% after iron treatment (p < 0.001 for all three parameters). Similar results were found in group B. Approximately three-quarters of all patients had only one iron infusion during the study period. Median time to reinfusion was 6 (1-25) months. Only previously described infusion reactions occurred in 27 (7%) patients. Conclusions. Adherence to European guidelines was rather poor and needs to be improved. The effect on iron parameters of intravenous FCM was significant, and resulted in a ferritin level that indicates an effect on the iron stores. The effect was mostly sustained for a year since only one-quarter of the patients were given repeated iron infusions. No unforeseen safety concerns emerged during the observation period.

BACKGROUND:Cyclosporine (CsA) or infliximab (IFX) are used as rescue therapies in steroid-refractory, severe attacks of ulcerative colitis (UC). There are no data comparing the efficacy of these two alternatives.METHODS:Outcome of rescue therapy was retrospectively studied in two cohorts of patients hospitalized due to steroid-refractory moderate to severe UC: 1) a Swedish-Danish cohort (n = 49) treated with a single infusion of IFX; 2) an Austrian cohort (n = 43) treated with intravenous CsA. After successful rescue therapy, maintenance immunomodulator treatment was given to 27/33 (82%) of IFX patients and to 31/40 (78%) of CsA patients. Endpoints were colectomy-free survival at 3 and 12 months. Kaplan-Meier and Cox regression models were used to evaluate the association between treatment groups and colectomy.RESULTS:At 15 days, colectomy-free survival in the IFX cohort was 36/49 (73%) versus 41/43 (95%) in the CsA cohort (P = 0.005), at 3 months 33/49 (67%) versus 40/43 (93%) (P = 0.002), and at 12 months 28/49 (57%) versus 33/43 (77%) (P = 0.034). After adjusting for potential confounding factors, Cox regression analysis yielded adjusted hazard ratios for risk of colectomy in IFX-treated patients of 11.2 (95% confidence interval [CI] 2.4-53.1, P = 0.002) at 3 months and of 3.0 (95% CI 1.1-8.2, P = 0.030) at 12 months in comparison with CsA-treated patients. There were no opportunistic infections or mortality.CONCLUSIONS:Colectomy frequencies were significantly lower after rescue therapy with CsA than with a single infusion of IFX both at 3 and 12 months' follow-up. The superiority of CsA was seen principally during the first 15 days.

Cyclosporin eller infliximab som rescue terapi vid steroidfraktar ulceros kolit : en retrospective observationsstudie

Outcome of rescue therapy in steroid-resistant ulcerative colitis : a retrospective study comparing cyclosporine and infliximab

Colectomy after rescue therapy for intravenous-steroid resistant acute ulcerative colitis : a 3-year follow-up study of the Swedish-Danish infliximab/placebo trial

irradiation magnetic field to tumor cells were established: 120 mT and 320 mT.The entrapment of magnetized immunocytes into tumor cells was verified with anti-CD8, -CD14, and -CD56 fluorescent antibodies.The production ability of IL4 and IFN was measured to evaluate the activation of magnetized immunocytes, and dead cell rate was determined by viability fluorescent multistaining to assess antitumor effect.Results: The APC and CTL combination group and the NK cell-alone group provided completely contrasting results with respect to their antitumor effect for HT29 and DLD1 cells.The death of not less than 40% of HT29 cells was successfully verified in the APC and CTL combination group.However, the death of HT29 cells could not be verified at all in the NK cell-alone group.Dead cells, when found, were NK cells.In contrast, the death of DLD1 cells could not be verified in the APC and CTL combination group.However, nearly 50% of NK cells died.In HT29 cells, furthermore, the antitumor effect-enhancing effect of the magnetized cytokine combination was effective in the APC and CTL group.In DLD1 cells, NK cells tended to be continuously effective; the activation of respective immunocytes and the enhancement of their antitumor effect were verified.Conclusions: Prolonged stay of magnetized immunocytes at the site of tumor was verified to enhance antitumor effect.Furthermore, our data suggested the magnetized cytokines' potential of controlling the negative feedback at the site of tumor.

A 2-year follow-up of the swedish-danish Infliximab/Placebo trial in steroid resistant acute ulcerative colitis

BACKGROUND & AIMS:Despite treatment with corticosteroids, severe to moderately severe attacks of ulcerative colitis have a high colectomy rate. We intended to find a rescue therapy other than cyclosporin A, which imposes a high risk of side effects and cyclosporine-related mortality.METHODS:This was a randomized double-blind trial of infliximab or placebo in severe to moderately severe ulcerative colitis not responding to conventional treatment. Patients were randomized to infliximab/placebo either on day 4 after the initiation of corticosteroid treatment if they fulfilled the index criteria for fulminant ulcerative colitis on day 3 or on day 6-8 if they fulfilled index criteria on day 5-7 for a severe or moderately severe acute attack of ulcerative colitis. Results were analyzed according to the intention-to-treat principle. The primary end point was colectomy or death 3 months after randomization. Secondary end points were clinical and endoscopic remission at that time in patients who did not undergo operation.RESULTS:Forty-five patients were included (24 infliximab and 21 placebo). No patient died. Seven patients in the infliximab group and 14 in the placebo group had a colectomy (P = .017; odds ratio, 4.9; 95% confidence interval, 1.4-17) within 3 months after randomization. No serious side effects occurred. Three patients in the placebo group required operation for septic complications.CONCLUSIONS:Infliximab 4-5 mg/kg is an effective and safe rescue therapy in patients experiencing an acute severe or moderately severe attack of ulcerative colitis not responding to conventional treatment.

UNNAR JÄRNEROT,* ERIK HERTERVIG, INGALILL FRIIS–LIBY, LARS BLOMQUIST, PER KARLÉN, HRISTER GRÄNNÖ, MOGENS VILIEN,** MAGNUS STRÖM, ÅKE DANIELSSON, ANS VERBAAN, PER M. HELLSTRÖM, ANDERS MAGNUSON, and BENGT CURMAN* Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden; Department of Medicine, Division of astroenterology, Lund University Hospital, Lund, Sweden; Department of Medicine, Division of Gastroenterology, Sahlgrenska University ospital, Gothenburg, Sweden; Department of Gastroenterology and Hepatology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Division of Gastroenterology, South Hospital, Stockholm, Sweden; Department of Medicine, Division of astroenterology, Ryhov Hospital, Jönköping, Sweden; **Department of Medicine, Division of Gastroenterology, West Zealand Hospital, lagelse, Denmark; Department of Molecular and Clinical Medicine, Division of Gastroenterology and Hepatology, Faculty of Health ciences, Linköping, Sweden; Department of Medicine, Division of Gastroenterology, Umeå University Hospital, Umeå, Sweden; Department of Medicine, Division of Gastroenterology, Malmö General University Hospital, Malmö, Sweden; and Unit of Statistics and pidemiology, Centre for Clinical Research, Örebro University Hospital, Örebro, Sweden

Evaluation of small bowel transit, which should preferably be performed using non-invasive techniques, is complex owing to the anatomical position of the small bowel. In order to avoid any influence of the gastric emptying rate on scintigraphic results, we have used 99mTc-HIDA, an intravenous tracer that is excreted in bile and thereby delivered directly into the duodenum. Thirty healthy subjects were studied after an overnight fast. Immediately after administration of 120 MBq 99mTc-HIDA, dynamic 1-min image acquisitions were begun. The duodenum and caecum were easily identified on the digitised images. Small bowel transit time was determined from the difference in the arrival times of the radiopharmaceutical in the proximal duodenum and caecum, as assessed by evaluation of the count rate against background activity (Scint 1) and by the visual appearance of activity (Scint 2). Hydrogen breath test was performed simultaneously to evaluate scintigraphic transit. Scintigraphic transit tests were also performed in 23 patients with motility disorders who had undergone manometry of the small bowel. In healthy subjects, the transit time of 99mTc-HIDA was 77.9±31.1 min (Scint 1) or 79.3±30.9 min (Scint 2) and the lactulose transit time was 100.1±43.4 min. Seventeen of the 23 patients had a dysmotility pattern verified by manometry, and in 14 of these patients, 99mTc-HIDA transit was prolonged. 99mTc-HIDA small bowel transit is a readily available method for the detection of transit abnormalities in the clinical setting. The method is clinically feasible and the transit time of 99mTc-HIDA shows a good correlation with results of the hydrogen breath test (lactulose transit time) in healthy volunteers.

Symptoms from the gastro-intestinal tract are common and often difficult to evaluate. Specialised examination techniques are available only at a limited number of clinics. A technique based on biliary scintigraphy when measuring the transit of contents through the small intestine has been developed. The investigation is simple to perform and convenient for the patient. It can be carried out at any clinic equipped with a gamma camera. 30 healthy individuals were examined in order to obtain reference values. 23 patients were examined with scintigraphy in combination with upper gastrointestinal manometry, 10 of whom had abdominal pain and neurogenic or myogenic pseudoobstruction disclosed by manometry. In another 4 patients, slow transit and pain prevailed in conjunction with normal manometric findings. Rapid transit and diarrhoea was found in 3 patients with various abberations on manometry. Of the remaining patients, 4 had slow transit and diarrhoea with intestinal neuropathy and pseudoobstruction, and 2 had slow transit along with endocrinopathies (diabetes, pituitary insufficiency).

BACKGROUND:Coeliac disease is an inflammatory disorder characterized by reversible atrophy of small intestinal villi following the ingestion of gluten. Earlier studies indicate that the inflammatory response to gluten may occur also very distally in the gastrointestinal tract. The aim of this study was to evaluate whether rectal challenge with gluten would trigger an increased local production of the gas nitric oxide (NO), a novel marker of intestinal inflammation.METHODS:Rectal challenge with partially digested gluten was performed in 20 patients with treated coeliac disease and in 13 healthy controls. Luminal levels of NO were measured in the rectum at 0, 8 and 24 h using a chemiluminescence technique.RESULTS:In patients with coeliac disease mean rectal NO increased from 235+/-90 parts per billion (ppb) at 0 h to 4965+/-1653 ppb at 24 h (P < 0.005). In the control group there was no significant increase. One control subject responded with high NO levels at 24 h and the same individual tested positive for anti-endomysium IgA antibodies. Subsequent duodenal biopsing showed substantial villusatrophy.CONCLUSIONS:Rectal challenge with gluten results in increased luminal levels of NO in a group of patients with treated coeliac disease. Further studies are needed to evaluate the role of NO in coeliac disease and the potential usefulness of rectal NO measurements in aiding diagnosis of this intestinal disorder.

Intestinal tight junction function is thought tobe of importance in the pathogenesis of variousdiseases. The regulation of uptake of macromolecules viathe tight junctions is largely unknown. Effects of luminal sodium caprate (10 mM), a dairyproduct constituent, and cytochalasin B (30 μM), werestudied in rat ileum in vitro in Ussing chambers. Bothagents caused a reversible fall in potential difference and increased [51Cr]EDTApermeability. In addition, sodium caprate inducedincreased permeability to polysucrose (15,000 daltons)and opening of the tight junctions as visualized bytransmission electron microscopy. Doseresponse patterns suggestedmainly dose-dependent differences between the agents.Confocal laser scanning microscopy suggestedparacellular permeation of polysucrose. Luminal sodiumcaprate, a food constituent, can increase tight junctionpermeability, allowing passage of macromolecules,without affecting epithelial viability. Increasedpermeability to mediumsized molecules does notnecessarily coincide with increased paracellular uptake ofproteinsized molecules.

Objective: To examine intestinal permeability to synthetic polysucrose in healthy humans and in rheumatoid arthritis patients with and without non-steroidal anti-inflammatory drug (NSAID) treatment. Design: Rheumatoid arthritis patients on NSAID treatment (n = 27) and age-matched healthy volunteers (n = 22) were given an oral dose of polysucrose with mean molecular weight of about 15 000, administered together with a tube feeding standard formula to mimick a meal. Urine was collected for 0-4, 4-8 and 8-12h. Seven of the rheumatoid arthritis patients also underwent the test before starting NSAID treatment. Methods: Intestinal permeability to polysucrose 15 000 was estimated as urinary excretion of the compound, measured by immunoassay. Results: In healthy volunteers urinary excretion of polysucrose 15 000 was about 0.02% of dose over 12 h. Intestinal permeability was significantly higher in the NSAID patients than in the non-NSAID patients or in the healthy volunteers. Intestinal permeability increased in all of the rheumatoid arthritis patients starting NSAID treatment during the study. Conclusions: Polysucrose 15 000 is suggested as a marker of intestinal paracellular permeability, especially to macromolecules, being neutral, water-soluble, non-lipid-soluble, non-toxic, non-immunogenic, of speherical molecular shape, and possible to produce over a wide range of molecular weights including those of several food proteins.