Microscopic colitis in patients with ulcerative colitis or Crohn's disease: a retrospective observational study and review of the literature.

OBJECTIVES: Onset of microscopic colitis (MC) in patients with ulcerative colitis (UC) or Crohn's disease (CD), or vice versa, has been reported occasionally but the subject is not well described. We therefore report a retrospective observational study of such patients and review the literature. METHODS: Forty-six Swedish gastroenterology clinics were contacted about patients with diagnoses of both inflammatory bowel disease (IBD) and MC. Publications were searched on PubMed. RESULTS: We identified 31 patients with onset of MC after a median (range) of 20 (2-52) years after diagnosis of IBD, or vice versa; 21 UC patients developed collagenous colitis (CC) (n = 16) or lymphocytic colitis (LC) (n = 5); nine CD patients developed CC (n = 5) or LC (n = 4); one CC patient developed CD. Of the 21 UC patients, 18 had extensive disease, whereas no consistent phenotype occurred in CD. Literature review revealed 27 comprehensive case reports of patients with diagnoses of both IBD and MC. Thirteen MC patients developed IBD, of which four required colectomy. Fourteen IBD patients later developed MC. There were incomplete clinical data in 115 additional reported patients. CONCLUSIONS: Altogether 173 patients with occurrence of both IBD and MC were found. The most common finding in our patients was onset of CC in a patient with UC. Although these are likely random associations of two different disorders, MC should be considered in the patient with UC or CD if there is onset of chronic watery diarrhoea without endoscopic relapse of IBD.

Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS.

OBJECTIVE: Bile acids may play a role in the pathogenesis of IBS. We investigated the potential effects of bile acids entering the colon and its role in the symptom pattern in IBS. DESIGN: We measured 75Se-labelled homocholic acid-taurine (75SeHCAT) retention, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor (FGF) 19 in patients with IBS (n=141) and control subjects (75SeHCAT n=29; C4 and FGF19 n=435). In patients with IBS stool frequency and form, as well as GI symptom severity were registered, and in a proportion of patients colonic transit time and rectal sensitivity were measured (n=66). An 8-week open-label treatment with colestipol was offered to patients with 75SeHCAT <20%, and the effect of treatment was evaluated with IBS severity scoring system and adequate relief of IBS symptoms. RESULTS: Compared with controls, patients with IBS had lower 75SeHCAT values (p=0.005), higher C4c levels (C4 corrected for cholesterol) (p<0.001), but similar FGF19 levels. Abnormal 75SeHCAT retention (<10%) was seen in 18% of patients, whereas 23% had elevated C4c levels. Patients with IBS with 75SeHCAT retention <10% had more frequent stools, accelerated colonic transit time, rectal hyposensitivity, a higher body mass index, higher C4c and lower FGF19 levels. Colestipol treatment improved IBS symptoms (IBS severity scoring system 220±109 vs. 277±106; p<0.01), and 15/27 patients fulfilled criteria for treatment response (adequate relief ≥50% of weeks 5-8). CONCLUSIONS: Increased colonic bile acid exposure influences bowel habit and colonic transit time in patients with IBS. A high response rate to open label treatment with colestipol supports this, but placebo-controlled studies are warranted.

Global mucosal and serum cytokine profile in patients with ulcerative colitis undergoing anti-TNF therapy.

BACKGROUND AND OBJECTIVE: The knowledge of the effects of anti-tumour necrosis factor (TNF) treatment on the global cytokine profile in patients with ulcerative colitis (UC) is limited. A better understanding of these mechanisms could improve the ability to select patients that should undergo the therapy. Therefore, the aim was to determine the global mucosal and serum cytokine profile before and during induction therapy with anti-TNF in UC patients. MATERIALS AND METHODS: In total, mucosal biopsies (n = 28) and serum samples (n = 42) were collected from UC patients (total n = 48) before anti-TNF therapy. At week 14 response to the therapy was evaluated and again mucosal biopsies (n = 14) and serum samples (n = 42) were collected. Quantitative real-time PCR was used to determine mucosal cytokine mRNA expression and the MSD MULTI-ARRAY assay system platform was used for analysis of cytokines in serum. The global cytokine profile was evaluated by multivariate factor analysis. RESULTS: At baseline, the global profile of mucosal cytokine mRNA expression and serum cytokines discriminated therapy responders from non-responders. Responders had lower mucosal mRNA expression of interleukin 1ß (IL-1ß), IL-17A, IL-6 and interferon γ (IFN-γ) than non-responders. Fourteen weeks after therapy start mucosal IL-1ß and IL-6 were down-regulated in therapy responders but not in non-responders. At week 14, serum levels of IL-6 were decreased in therapy responders whereas IFN-γ and IL-12p70 were increased in non-responders. CONCLUSIONS: Our data suggest that patients with a therapy failure have a more severe pro-inflammatory cytokine profile before start of anti-TNF treatment, which is less well suppressed by the treatment as compared to therapy responders.

Endoscopic papillectomy and KRAS expression in the treatment of adenoma in the major duodenal papilla.

OBJECTIVE: The use of endoscopic papillectomy for resecting adenomas in the major duodenal papilla is increasing. This study focuses on the following three issues: Can endoscopic papillectomy be performed as a safe diagnostic and/or therapeutic procedure in biopsy-verified or suspected ampullary adenoma? Does expression of mutated KRAS in resected adenomatous tissue predict long-term outcome? What other factors may affect long-term outcome and should, therefore, be considered in decision making prior to endoscopic papillectomy? MATERIAL AND METHODS: Thirty-six prospectively collected patients who underwent endoscopic papillectomy at Karolinska University Hospital between 2005 and 2014 were analyzed. RESULTS: The rate of exact agreement between the histomorphological grading of the endoscopic biopsies and the papillectomy specimens was low (48%). Obstructive jaundice at presentation increased the risk of undetected adenocarcinoma (RR = 3.98; 95% CI = 1.46-10.85, p = 0.007). Lesions with malignancies were significantly larger (mean 30.6 mm) than those where only adenomas were found (mean 14.4 mm, p = 0.001). Mutated KRAS was detected in 9 of the 36 post-papillectomy specimens, including 4 of the 5 cases of ampullary adenocarcinoma. Eighteen cases were endoscopically cured after a mean follow-up period of 47 months (range 16-92 months). CONCLUSIONS: Endoscopic papillectomy is a valuable staging tool because of the limitations of endoscopic biopsy. Endoscopic papillectomy concomitantly offers a curative treatment for most patients with adenoma in the major duodenal papilla. Jaundice at presentation and large adenomas may indicate the presence of more advanced disease. Determination of mutated KRAS seems to be of limited value in predicting long-term outcome.

Faecal microbiota transplantation and bacteriotherapy for recurrent Clostridium difficile infection: a retrospective evaluation of 31 patients.

BACKGROUND: Recurrent Clostridium difficile infection (CDI) is a significant problem due to its increased incidence and severity. Failure rates for standard antibiotic therapies are high. In our hospital, faecal microbiota transplantation (FMT), or instillation of a culture mixture of known enteric bacteria in saline as rectal bacteriotherapy (RBT), has long been used as 'rescue therapy' in patients with recurrent disease, in whom repeated courses of standard antibiotic treatment have failed. We wanted to evaluate the effectiveness of FMT and RBT for recurrent CDI. METHODS: The records of 31 patients treated with either FMT or RBT for recurrent CDI were reviewed retrospectively. FMT was based on faecal donation by a close relative and RBT on a defined saline mixture of 10 individually cultured enteric bacterial strains originally isolated from healthy persons. Both types of instillation were carried out through a rectal catheter. FMT (500 ml) was given as 1 installation. RBT (200 ml) was given as 2 or 3 installations with an interval of 2 days between courses. Treatment success was defined as a sustained loss of symptoms and discontinuation of diarrhoea within 3 days. RESULTS: Of 31 patients, 23 (74%) responded successfully to the treatment: 16 of 23 (70%) receiving FMT and 7 of 8 (88%) receiving RBT. CONCLUSION: We found FMT to be effective in patients with recurrent CDI. RBT based on a predefined bacterial suspension was as effective as or better than FMT based on faecal donation; however, multiple installations may be needed.

Covered and uncovered self-expandable metallic Hanarostents are equally efficacious in the drainage of extrahepatic malignant strictures. Results of a double-blind randomized study.

BACKGROUND: Self-expandable metallic stents (SEMS) placement is a standard treatment for inoperable malignant bile duct strictures. Covered SEMS have been introduced to avoid stent occlusion by tumor ingrowth. The aims were to compare covered and uncovered stents in terms of patency, efficacy and complication rate. MATERIAL AND METHODS: Consecutive patients with inoperable malignant distal biliary strictures were included in the study and randomized to receive a covered (n = 34) or uncovered (n = 34) Hanaro SEMS. Follow-up was performed by nurses after 18 h, 48 h, 2 weeks and thereafter every month until stent dysfunction or the patient died. Outcomes were measured as follows: the patients reported urine and stool color, presence of fever and abdominal pain. Liver function tests and CRP were analyzed each time. The procedure time and complications were monitored. The follow-up was blinded to stent type. RESULTS: The median patient age was 79 years (IQR: 66-83, R: 54-92), 59% were female and 85% had the gallbladder in situ. There was no difference between covered and uncovered stents in terms of procedure time (median: 30 min (20-38, R: 12-90) vs. 30 min (IQR: 20-42, R: 12-70)), stent patency (median: 153 days (IQR: 65-217; R: 20-609) vs. median of 127 days (IQR: 70-196; R: 18-486)) or patient survival (median: 154 days (IQR: 65-217; R: 21-609) vs 157 days (IQR: 70-273, R: 20-690)). Eighty-seven percent died with a patent covered and 83% with an uncovered stent (n.s.). Two early complications occurred (sepsis; pancreatitis), both with covered stents. CONCLUSION: There is no clinical difference between covered and uncovered biliary Hanaro SEMS. Both types are easily inserted with low complication rate and have long-term patency.

A preventive effect of unfractionated heparin on post-ERCP pancreatitis is suggested by positive effects on laboratory markers.

BACKGROUND/AIMS: Heparin has anti-inflammatory properties. Serum tests after ERCP might serve as surrogate markers for inflammatory reactions. The aims were to study effects of low-dose unfractionated heparin on post-ERCP laboratory tests and on safety. METHODOLOGY: The design was prospective, randomized, double-blind, placebo-controlled. Eighty-nine patients were randomized to 5000 IE Heparin (0.2 ml of 25000 IE) or 0.2 ml 0.9% NaCL given s.c. 4h before and 4h and 18h after ERCP. Amylase, AST, ALT, CRP and leucocyte count were analyzed at these times and also after 48h. Adverse events were registered. RESULTS: Significant increase was observed after 18h in the placebo group (n=44) for amylase (mean: 0.66 microkat/l, SD:0.8 vs. mean: 4.56 microkat/l, SD:9.9, p = 0.011), AST (mean: 1.37 microkat/l, SD: 1.5 vs. mean: l.96 microkat/l, SD:2.1, p = 0.049) and ALT (mean: 2.42 microkat/l, SD:2.7 vs. mean: 2.91, SD: 2.9% kat/l, p = 0.042). Corresponding elevations were not seen in the heparin group (n=41): p = 0.371, 0.395 and 0.25 respectively. Leucocyte count elevation was higher with longer duration in the placebo group. Mild pancreatitis occurred in 4.7% (placebo: 3, heparin: (1) and 4/89 (placebo: 2, heparin:(2) were excluded due to minor bleeding after the first injection. CONCLUSIONS: Low-dose heparin reduces the characteristic rise in laboratory tests seen after ERCP. Larger studies with acute pancreatitis as the end-point are justified.

Biliary sphincterotomy does not relate to diarrhoea or major changes in bile acid synthesis or plasma lipids.

OBJECTIVES: Bile acid (BA) malabsorption may occur after cholecystectomy. Bile may flow more freely into the duodenum after endoscopic sphincterotomy (EST), in part resembling the situation after cholecystectomy. The (75)SeCHAT test used to diagnose BA malabsorption correlates inversely with synthesis and faecal excretion of BAs. The BA intermediate 7alpha-hydroxy-4-cholesten-3-one (C4) mirrors BA and lathosterol cholesterol synthesis. The aim was to study whether EST causes BA diarrhoea and alterations in BA synthesis or lipid profiles. MATERIAL AND METHODS: Twelve patients underwent the (75)SeHCAT test prior to and 3 months after undergoing EST and a further 22 only after EST. The Gastrointestinal Symptom Rating Scale (GSRS), 1 week daily stool frequency and consistency, C4, lathosterol, cholesterol and triglycerides were investigated. The (75)SeHCAT values of 29 healthy subjects served as controls. RESULTS: Stool frequency (median 1/day, IQR (interquartile range): 0.7) and consistency (median: 3, IQR: 0.65) were normal and none reported diarrhoea after EST (n=34). The GSRS scores were normal. There was no significant change in (75)SeHCAT (median 22%, IQR 29% versus 19.5%, IQR 25, n=12). There was a trend towards lower (75)SeHCAT after EST compared with the controls (median 26%, IQR 32, n=34 versus median 38%, IQR 19.5, n=29, p=0.075) and higher lathosterol (median 47.1 mg/mole, IQR 32.7 versus median 52.5 mg/mole, IQR 35.6, n=14, p=0.055). The C4 and lipids did not change significantly. CONCLUSIONS: EST did not induce diarrhoea and in line with this BA synthesis and serum lipids are unaltered.

Intravenous iron sucrose is superior to oral iron sulphate for correcting anaemia and restoring iron stores in IBD patients: A randomized, controlled, evaluator-blind, multicentre study.

OBJECTIVE: Patients with inflammatory bowel disease (IBD) often have low iron stores or anaemia. There is controversy about whether iron should be supplemented orally or intravenously (i.v.). The purpose of this study was to investigate whether treatment with intravenous iron is superior to treatment with oral iron. The primary end-points were response and remaining anaemia at the end of treatment (EOT). MATERIAL AND METHODS: Ninety-one patients with IBD and anaemia (B-Hb <115 g/L) were randomized to oral iron sulphate (n=46) or intravenous iron sucrose (n=45) treatment for 20 weeks. RESULTS: Forty-three patients in the intravenous iron group completed the study compared to 35 patients in the oral iron group (p=0.0009). Only 22 patients (48%) tolerated the prescribed oral dose, and 52% reduced the dose or withdrew from treatment because of poor tolerance. At EOT, 47% patients in the oral iron group increased their B-Hb by > or =20 g/L, compared with 66% in the intravenous iron group (p=0.07). In the oral iron group, 41% still had anaemia versus 16% of the patients in the intravenous iron group (p=0.007), and 22% versus 42% reached their reference B-Hb level (p=0.04). Treatment with intravenous iron sucrose improved iron stores faster and more effectively than oral iron (p=0.002). Under treatment with intravenous iron, 74% of the patients had no anaemia and normal S-ferritin levels (>25 microg/L) at EOT compared with 48% of patients receiving oral iron (p=0.013). CONCLUSIONS: Treatment with intravenous iron sucrose is effective, safe, well tolerated and superior to oral iron in correcting haemoglobin and iron stores in patients with IBD.

Hospital Design with Nature Films Reduces Stress-Related Variables in Patients Undergoing Colonoscopy.

PURPOSE: To examine whether patients' experiences could be improved during colonoscopy by designing the examination room to include a digital screen showing calm nature films. BACKGROUND: Colonoscopy is the gold standard for examination of the large intestine and the rectum. Around 50% of individuals invited for colorectal cancer screening choose to refrain from the screening due to fear and anxiety. It is therefore important to improve patients' comfort during the procedure. METHOD: One of the four endoscopy rooms was rebuilt to include a large digital screen showing calm nature films. Patients were randomized to intervention (i.e., the room showing films) or control. During the colonoscopy, pulse and oxygen saturation were measured and the patients graded the intensity of pain and anxiety. Blood samples were taken regularly during the examination and were analyzed for glucose, cortisol, and prolactin. RESULTS: The presence of calm nature films during colonoscopy decreased the release of cortisol, increased prolactin levels, and enhanced oxygen saturation. These effects were more apparent in patients who were unfamiliar with the procedure and the environment, patients who underwent the examination without analgesics or sedation, and patients whose examination procedure was relatively difficult and took a long time. CONCLUSIONS: The intervention described in this study is easy to implement and might help improve the patient experience during colonoscopy. However, this study was performed in a single health institution, and more studies are needed to further explore the role of film interventions in endoscopic and other medical procedures.

Brush cytology is superior to biopsies obtained by a new device in bile duct strictures.

BACKGROUND/AIMS: Brush cytology during ERCP has been reported to have a low sensitivity. A new device, Howell biliary system (Wilson-Cook), enables targeted biopsies for histopathologic assessment. The aim was to compare histopathology with brush cytology. METHODOLOGY: Brush cytology followed by biopsies obtained by the Howell device was taken consecutively from bile duct strictures. Coded slides were scored by 3 pathologists and 2 cytologists in a 3-graded scale; 2: benign; 3: suspicious of malignancy; 4: malignant. The clinical outcome including autopsy served as the gold standard for the definite diagnoses. RESULTS: Twenty-one malignant and 6 benign strictures were evaluated. The histopathology revealed 11 out of the 21 malignant as certain or suspected malignant (score > or = 3) (sensitivity: 0.52). The cytology scored 17 out of 21 > or = 3 (sensitivity: 0.80). The in pair kappa values for the 3 pathologists were: (0.37; 0.26; 0.41) vs. 0.56 for the 2 cytologists. Among the evaluable strictures the pathologists scorings were; (median: 3.0, SD: 0.72) for the malignant and (median: 2.3, SD: 0.98) for the benign (p = 0.27) and the cytology scorings were; (median: 3.5, SD: 0.73) for the malignant and (median: 2.7, SD: 0.65) for the benign (p = 0.09). CONCLUSIONS: Brush cytology has a higher accuracy than the targeted biopsies and should be used in combination with other methods to reach the correct diagnosis.

Normal or increased bile acid uptake in isolated mucosa from patients with bile acid malabsorption.

INTRODUCTION: Bile acid malabsorption as reflected by an abnormal Se-labelled homocholic acid-taurine (SeHCAT) test is associated with diarrhoea, but the mechanisms and cause-and-effect relations are unclear. OBJECTIVES: Primarily, to determine whether there is a reduced active bile acid uptake in the terminal ileum in patients with bile acid malabsorption. Secondarily, to study the linkage between bile acid malabsorption and hepatic bile acid synthesis. METHODS: Ileal biopsies were taken from patients with diarrhoea and from controls with normal bowel habits. Maximal active bile acid uptake was assessed in ileal biopsies using a previously validated technique based on uptake of C-labelled taurocholate. To monitor the hepatic synthesis, 7alpha-hydroxy-4-cholesten-3-one, a bile acid precursor, was assayed in blood. The SeHCAT-retention test was used to diagnose bile acid malabsorption. RESULTS: The taurocholate uptake in specimens from diarrhoea patients was higher compared with the controls [median, 7.7 (n=53) vs 6.1 micromol/g per min (n=17)] (P<0.01) but no difference was seen between those with bile acid malabsorption (n=18) versus diarrhoea with a normal SeHCAT test (n=23). The SeHCAT values and 7alpha-hydroxy-4-cholesten-3-one were inversely correlated. CONCLUSIONS: The data do not support bile acid malabsorption being due to a reduced active bile acid uptake capacity in the terminal ileum.

Anti-TNF Therapy Response in Patients with Ulcerative Colitis Is Associated with Colonic Antimicrobial Peptide Expression and Microbiota Composition.

BACKGROUND AND AIMS: Anti-tumour necrosis factor [TNF] therapy is used in patients with ulcerative colitis [UC], but not all patients respond to treatment. Antimicrobial peptides [AMPs] and the gut microbiota are essential for gut homeostasis and may be important for treatment outcome. The aim of this study was to determine AMP and microbiota profiles in patients with UC before anti-TNF therapy start and correlate these data to treatment outcome. METHODS: Serum and biopsies were obtained from UC patients naïve to biological therapy [n = 56] before anti-TNF therapy start [baseline]. Fecal samples were taken at baseline and Weeks 2 and 6. Quantitative proteomic analysis was performed in mucosal biopsies. Expression of AMPs and cytokines was determined in biopsies and serum. Microbiota analysis of fecal samples was performed using GA-map™ Dysbiosis Test and real-time quantitative polymerase chain reaction [rtPCR]. Treatment response was evaluated 12-14 weeks after baseline. RESULTS: At baseline, proteomic analysis of biopsies showed that treatment responders and non-responders had differential expression of AMPs. Eleven AMP and AMP-related genes were analysed by rtPCR in mucosal biopsies and could together discriminate responders from non-responders at baseline. The most important nominators for response were increased expression of defensin 5 and eosinophilic cationic protein. Microbiota analysis revealed lower dysbiosis indexes and higher abundance of Faecalibacterium prausnitzii in responders compared with non-responders at baseline. Also, abundance of F. prausnitzii increased during induction therapy in responders. CONCLUSIONS: Anti-TNF therapy responders and non-responders display distinctly separate patterns of mucosal AMP expression and gut microbiota before treatment start. This indicates that intestinal antimicrobial/microbial composition can influence treatment outcome.

Response to infliximab therapy in ulcerative colitis is associated with decreased monocyte activation, reduced CCL2 expression and downregulation of Tenascin C.

BACKGROUND AND AIMS: The cellular mechanisms leading to infliximab therapy response in patients with ulcerative colitis (UC) are incompletely known. We therefore investigated early effects of infliximab therapy on monocytes and associated chemokines linked to clinical therapy response in UC patients. METHODS: Blood and biopsies were obtained from anti-TNF therapy-naïve UC patients (n = 43) before (baseline) and during induction therapy with infliximab. Therapy response was evaluated at Week 14. Expression of monocyte activation markers and levels of chemokines in serum and biopsies were determined. Quantitative proteomic analysis was performed in cultured mucosal biopsies, and obtained data was validated in serum. RESULTS: In therapy responders, but not in non-responders, infliximab reduced blood monocyte expression of CD14 and CD86, 2 weeks after therapy commenced, relative to baseline. Serum CCL2 levels were decreased only among therapy responders at Week 2 and Week 14, relative to baseline. These data corresponded with lower levels of CD14, CD86 and CCL2 in intestinal tissue in responders as compared with non-responders at Week 14. Proteomic analysis of cultured biopsies showed that infliximab induced a reduction in Tenascin C that predicted downregulation of CCL2. Therapy responders, but not non-responders, had decreased serum Tenascin C levels at Week 2 and Week 14, relative to baseline. CONCLUSIONS: Infliximab therapy response in UC patients is associated with reduced monocyte activation and serum levels of CCL2 2 weeks after therapy commencement. In therapy responders, infliximab influenced Tenascin C, which might be a regulator of CCL2 expression and important for induction of the clinical therapy response.

Pharmacological intervention based on fecal calprotectin levels in patients with ulcerative colitis at high risk of a relapse: A prospective, randomized, controlled study.

BACKGROUND: Targeted therapy, using biomarkers to assess disease activity in ulcerative colitis (UC), has been proposed. OBJECTIVE: The objective of this study was to evaluate whether pharmacological intervention guided by fecal calprotectin (FC) prolongs remission in patients with UC. METHODS: A total of 91 adults with UC in remission were randomized to an intervention group or a control group. Analysis of FC was performed monthly, during 18 months. A FC value of 300 µg/g was set as the cut-off for intervention, which was a dose escalation of the oral 5-aminosalicylate (5-ASA) agent. The primary study end-point was the number of patients to have relapsed by month 18. RESULTS: There were relapses in 18 (35.3%) and 20 (50.0%) patients in the intervention and the control groups, respectively (p = 0.23); and 28 (54.9%) patients in the intervention group and 28 (70.0%) patients in the control group had a FC > 300 µg/g, of which 8 (28.6%) and 16 (57.1%) relapsed, respectively (p < 0.05). CONCLUSION: Active intervention significantly reduced relapse rates, although no significant difference was reached between the groups overall. Thus, FC-levels might be used to identify patients with UC at risk for a flare, and a dose escalation of their 5-ASA agent is a therapeutic option for these patients.

Nabumetone: therapeutic use and safety profile in the management of osteoarthritis and rheumatoid arthritis.

Nabumetone is a nonsteroidal anti-inflammatory prodrug, which exerts its pharmacological effects via the metabolite 6-methoxy-2-naphthylacetic acid (6-MNA). Nabumetone itself is non-acidic and, following absorption, it undergoes extensive first-pass metabolism to form the main circulating active metabolite (6-MNA) which is a much more potent inhibitor of preferentially cyclo-oxygenase (COX)-2. The three major metabolic pathways of nabumetone are O-demethylation, reduction of the ketone to an alcohol, and an oxidative cleavage of the side-chain occurs to yield acetic acid derivatives. Essentially no unchanged nabumetone and < 1% of the major 6-MNA metabolite are excreted unchanged in the urine from which 80% of the dose can be recovered and another 10% in faeces. Nabumetone is clinically used mainly for the management of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) to reduce pain and inflammation. The clinical efficacy of nabumetone has also been evaluated in patients with ankylosing spondylitis, soft tissue injuries and juvenile RA. The optimum oral dosage of nabumetone for OA patients is 1 g once daily, which is well tolerated. The therapeutic response is superior to placebo and similar to nonselective COX inhibitors. In RA patients, nabumetone 1 g at bedtime is optimal, but an additional 0.5-1 g can be administered in the morning for patients with persistent symptoms. In RA, nabumetone has shown a comparable clinical efficacy to aspirin (acetylsalicylic acid), diclofenac, piroxicam, ibuprofen and naproxen. Clinical trials and a decade of worldwide safety data and long-term postmarketing surveillance studies show that nabumetone is generally well tolerated. The most frequent adverse effects are those commonly seen with COX inhibitors, which include diarrhoea, dyspepsia, headache, abdominal pain and nausea. In common with other COX inhibitors, nabumetone may increase the risk of GI perforations, ulcerations and bleedings (PUBs). However, several studies show a low incidence of PUBs, and on a par with the numbers reported from studies with COX-2 selective inhibitors and considerably lower than for nonselective COX inhibitors. This has been attributed mainly to the non-acidic chemical properties of nabumetone but also to its COX-1/COX-2 inhibitor profile. Through its metabolite 6-MNA, nabumetone has a dose-related effect on platelet aggregation, but no effect on bleeding time in clinical studies. Furthermore, several short-term studies have shown little to no effect on renal function. Compared with COX-2 selective inhibitors, nabumetone exhibits similar anti-inflammatory and analgesic properties in patients with arthritis and there is no evidence of excess GI or other forms of complications to date.

Role of bile acids in lymphocytic colitis.

BACKGROUND/AIMS: A high prevalence of bile acid malabsorption and a high response rate to bile acid binders are seen in collagenous colitis. Our aim was to explore if bile acids play a role in lymphocytic colitis, which is unknown. METHODOLOGY: Patients with lymphocytic colitis completed a diagnostic program, including the 75SeHCAT (75Se-labelled homocholic acid-taurine) test and registration of symptoms. Prevalence of bile acid malabsorption, response to bile acid binders, correlation between 75SeHCAT and histopathology were determined. The 75SeHCAT values were compared with 29 controls. RESULTS: Two out of 23 with lymphocytic colitis had a 75SeHCAT retention < or = 10%. The median 75SeHCAT value in lymphocytic colitis, 24% (range: 1.7-53), was lower than in the control group, 38% (range: 8-91) (P < 0.02). Forty-six per cent (6/13) responded to bile acid binders. No correlation was found between the 75SeHCAT values and degree of colonic inflammation. Two patients developed collagenous colitis. CONCLUSIONS: Bile acid malabsorption is more uncommon in lymphocytic colitis than in collagenous colitis. The 75SeHCAT values, however, suggest a role of bile acids in lymphocytic colitis. The conversion of 2 patients to collagenous colitis and disturbed absorption of bile acids also in lymphocytic colitis is consistent with the idea that the two forms represent variants of the same disease.

Fecal calprotectin one year after ileocaecal resection for Crohn's disease--a comparison with findings at ileocolonoscopy.

BACKGROUND AND AIMS: Ileocaecal resection for Crohn's disease is commonly performed. The severity of endoscopic lesions in the anastomotic area one year postoperatively is considered to reflect the subsequent clinical course. Fecal calprotectin (FC) has been shown to correlate with the findings at ileocolonoscopy in Crohn's disease. The objectives of this study were to assess whether the concentration of FC reflects the endoscopic findings one year after ileocaecal resection and to evaluate the variation of FC in individual patients during 6months prior to the ileocolonoscopy. METHODS: Thirty patients with Crohn's disease and ileocaecal resection performed within one year were included. Stool samples were delivered monthly until an ileocolonoscopy was performed one year postoperatively. RESULTS: One year after surgery the median values of FC were not significantly different between the patients in endoscopic remission (n=17) and the patients with an endoscopic recurrence (189 (75-364) vs 227 (120-1066)µg/g; p=0.25). However, most patients with low values were in remission and all patients with high (>600µg/g) calprotectin values had recurrent disease. The variability of the FC concentration was most pronounced in patients with diarrhea. CONCLUSIONS: We found no statistical difference in the concentrations of calprotectin between patients in endoscopic remission and patients with a recurrent disease one year after ileocaecal resection for Crohn's disease. However, among the minority of patients with low or high values, FC indicated remission and recurrence, respectively. There was significant variation of the fecal calprotectin concentrations over time, which affects the utility of calprotectin in clinical practice.

CD25 and TNF receptor II reflect early primary response to infliximab therapy in patients with ulcerative colitis.

BACKGROUND: Although infliximab treatment is an option for patients with ulcerative colitis (UC), not all patients do respond to therapy, and cellular mechanisms leading to therapy response are incompletely known. OBJECTIVE: The objective of this article is to determine early effects of infliximab therapy on T cells in the blood of UC patients and if effects differed in therapy responders and nonresponders. METHODS: Blood samples were obtained before and two weeks post-treatment start from 34 anti-tumor necrosis factor (TNF) therapy-naïve UC patients undergoing infliximab therapy. Response to therapy was evaluated prior to the fourth treatment dose. Expression of T cell surface markers and levels of soluble receptors and cytokines in serum were determined. RESULTS: At baseline, there were no differences in cellular, biochemical or clinical parameters between therapy responders and nonresponders. Infliximab therapy reduced frequencies of CD25(+) T cells and increased frequencies of annexin V(+) T cells in patients responding to infliximab, but not in nonresponding patients, two weeks after therapy start. Only therapy responders had decreased serum levels of sCD25 and sTNFRII two weeks after treatment start. In contrast, clinical parameters did not reflect therapy outcome already two weeks after therapy start. CONCLUSION: Soluble and membrane-bound T cell receptors may be early indicators of infliximab therapy response in UC, which can be of clinical importance for the decision when to continue or to stop the treatment.