| 1. |
- Jarvis, Erich D., et al.
(författare)
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Whole-genome analyses resolve early branches in the tree of life of modern birds
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1320-1331
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Tidskriftsartikel (refereegranskat)abstract
- To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.
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| 2. |
- Münch, Andreas, et al.
(författare)
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Adalimumab in budesonide and methotrexate refractory collagenous colitis
- 2012
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 47:1, s. 59-63
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Tidskriftsartikel (refereegranskat)abstract
- Background. We described three patients with collagenous colitis (CC) who developed side effects or were refractory to both budesonide and methotrexate and were given adalimumab (ADA) as a third-line treatment. Method/Patients. Three patients (two women, mean age 45 years and one man, 74 years old) were included. Mean bowel movements per day per week were calculated and stool weight/24 h registered prior to and following ADA treatment. ADA was given in doses 160 mg s.c. (baseline), 80 mg (week 2) and 40 mg (week 4). Sigmoidoscopies with biopsies were performed at baseline and after 6 weeks to examine changes in histology. The Psychological General Well-Being Index (PGWBI) and Short Health Scale (SHS) were used at baseline and after 6 weeks. Results. The two female patients tolerated the treatment well. The male patient developed, despite clinical response, side effects (vomiting, abdominal pain) after 80 mg of ADA and the treatment was stopped as side effects reoccurred after rechallenge. The two women were in clinical remission at week 6 and the mean stool frequency per day decreased from mean 11 to 2. Mean stool weight/24 h changed from 600 to 185 g. The quality of life improved drastically in all patients. There were no consistent changes in histology. Conclusion. ADA seems effective in budesonide and methotrexate refractory CC and can be administrated to selected patients to achieve clinical remission, improve quality of life and possibly avoid colectomy. Further studies for induction and maintenance treatment should be conducted to confirm efficacy and examine safety issues, even in long term
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| 3. |
- Münch, Andreas
(författare)
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Collagenous colitis : The influence of inflammation and bile acids on intestinal barrier function
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Collagenous colitis (CC) is a diarrheal disorder with an incidence rate of 5-6/100000 inhabitants, affecting mainly middle-aged women. The diagnosis is made by histology of the colonic mucosa. Classical findings are a thickened subepithelial collagenous layer and chronic inflammation in the lamina propria. In inflammatory bowel disease (IBD) the mucosal barrier function is important in pathogenesis. The main purpose of the thesis was therefore to describe the barrier function in CC. The cause of CC is uncertain but the condition seems to be associated with bile acid malabsorption. Increased faecal bile acids are known to induce diarrhea. In functional studies the influence of bile acids on mucosal permeability in biopsies of healthy human individuals and in patients with CC was investigated.Methods and patients: In the first paper a single patient with intractable CC was examined before surgery, with loop-ileostomy and after bowel reconstruction. For the other studies a total of 25 patients with CC were included (20 women, 5 men, mean age 66 years). There were three groups (14 patients in clinical remission without medical treatment, 11 with active disease, and 8 of these again after 6 weeks of budesonide treatment); 17 individuals with normal histology served as controls. Endoscopic biopsies from the sigmoid colon were mounted in modified Ussing chambers and assessed for short-circuit current (Isc), transepithelial resistance (TER), and transmucosal passage of chemically killed E. coli K12 after addition of chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA). The biopsies were further investigated with confocal microscopy to assess bacterial transepithelial passage.Results: Para- and transcellular permeability was increased in active CC, but normalized with histological improvement due to faecal stream diversion. After bowel reconstruction, permeability to CrEDTA and HRP increased again.In CC, bacterial uptake in colonic biopsies was significantly higher in all groups than in controls. Despite significant alleviation of symptoms, budesonide did not normalize the increased bacterial passage. Histology was unchanged after 6 weeks of budesonide treatment. DCA augmented mucosal permeability to CrEDTA in a dose-dependent manner and even such a low dose as 100 μmol/l DCA increased bacterial uptake significantly. The combination of bile acids and E.coli K12 had additive effects on TER.100 μmol/l CDCA and DCA increased bacterial uptake in biopsies of CC patients in remission 4-fold, but had no additive effect on biopsies from patients with active disease. Furthermore, patients in clinical remission on budesonide treatment showed no bile acidinduced effects on E.coli K12 passage.Conclusion: Collagenous colitis presents with increased para/transcellular permeability and bacterial uptake, irrespective of disease activity or budesonide treatment, signifying an underlying mucosal barrier defect. Faecal stream diversion can normalize the barrier dysfunction, but budesonide does not, despite its beneficial clinical effects which alleviate diarrhea or bowel symptoms. Bile acids in physiological concentrations have the potential to augment bacterial uptake, especially in mucosa from CC patients in remission. Budesonide treatment appears to counteract the bile acid induced mucosal impairment. These detrimental effects of bile acids on mucosal barrier function might facilitate initiation and perpetuation of mucosal inflammation in CC.
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| 4. |
- Munch, Andreas, et al.
(författare)
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Lack of effect of methotrexate in budesonide-refractory collagenous colitis
- 2013
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Ingår i: Clinical and Experimental Gastroenterology. - : Dove Medical Press. - 1178-7023. ; 6, s. 149-152
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:In most cases, collagenous colitis can be treated effectively with budesonide. However, some patients develop side effects or have chronic symptoms refractory to budesonide. This paper reports an open case series of patients intolerant or refractory to budesonide who were treated with methotrexate (MTX).METHODS AND PATIENTS:Nine patients (seven women) with a median (range) age of 62 (44-77) years were studied. Bowel movements were registered during 1 week prior to baseline and after 6 and 12 weeks' treatment, enabling calculation of the mean bowel movements/day. All patients underwent colonoscopy with biopsies before inclusion to confirm diagnosis. Open treatment with MTX was given 15 mg subcutaneously weekly for 6 weeks and was increased to 25 mg for a further 6 weeks if symptoms were unresponsive to the first 6 weeks' treatment. The endpoint was clinical remission, which was defined as a mean <3 stools/day and mean <1 watery stool/day/week at Week 12. The Short Health Scale was used at baseline and Week 12 to assess health-related quality of life.RESULTS:Five patients fulfilled the treatment according to the protocol and four patients discontinued the study after 3-6 weeks because of adverse events. No patient achieved clinical remission at Week 12. The mean stool frequency/day at baseline was 6.0 stools/day, thereof 5.4 watery stools/day and after 12 weeks treatment 6.4 stools/day, thereof 5.7 watery/day. No patient appreciated an improvement of health-related quality of life.CONCLUSION:Short-term treatment with MTX had no clinical effect in collagenous colitis patients intolerant or refractory to budesonide. Alternative therapies should be investigated in these patients.
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| 5. |
- Munch, Andreas, et al.
(författare)
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Low levels of bile acids increase bacterial uptake in colonic biopsies from patients with collagenous colitis in remission
- 2011
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Ingår i: ALIMENTARY PHARMACOLOGY and THERAPEUTICS. - : Blackwell Publishing Ltd. - 0269-2813. ; 33:8, s. 954-960
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Tidskriftsartikel (refereegranskat)abstract
- Pandgt;Background Patients with collagenous colitis have an impaired mucosal barrier. Moreover, collagenous colitis is associated with bile acid malabsorption. Bile acids can increase bacterial mucosal uptake in humans. Mucosal barrier function was investigated by exposing colonic biopsies to chenodeoxycholic acid (CDCA) or deoxycholic acid (DCA) in Ussing chamber experiments. Aim To find if low levels of bile acids increase bacterial uptake in colonic biopsies from collagenous colitis patients. Methods The study comprised 33 individuals; 25 with collagenous colitis (14 in clinical remission without treatment, 11 with active disease and 10 examined in clinical remission resulting from treatment with 6 mg budesonide); eight healthy individuals undergoing screening colonoscopy served as controls. Endoscopic biopsies from the sigmoid colon were mounted in modified Ussing chambers and assessed for short-circuit current (Isc), potential difference, trans-epithelial resistance and transmucosal passage of Escherichia coli K12 after adding 100 mu mol/L CDCA or DCA. Results When adding 100 mu mol/L CDCA or DCA, bacterial uptake increased fourfold in biopsies of patients in remission; CDCA 6.5 units [2.5-9.8] and DCA 6.2 units [2.1-22] (median [IQR]), compared with uptake in biopsies without added bile acids 1.6 units [1.1-3] (P = 0.004 and P = 0.01 respectively). In active disease and in patients in remission due to budesonide treatment, bile acids did not affect bacterial uptake. Confocal microscopy revealed trans-epithelial passage of E. coli K12 within 30 min. Conclusions Low concentrations of dihydroxy-bile acids exacerbate mucosal barrier dysfunction in colonic biopsies of patients with collagenous colitis in remission. This allows a substantially increased bacterial uptake, which may contribute to recurrence of inflammation.
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| 6. |
- Münch, Andreas, et al.
(författare)
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Microscopic colitis : Current status, present and future challenges Statements of the European Microscopic Colitis Group
- 2012
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Ingår i: Journal of Crohn's & Colitis. - Amsterdam, Netherlands : Elsevier. - 1873-9946 .- 1876-4479. ; 6:9, s. 932-945
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Tidskriftsartikel (refereegranskat)abstract
- Microscopic colitis (MC) is an inflammatory bowel disease presenting with chronic, non-bloody watery diarrhoea and few or no endoscopic abnormalities. The histological examination reveals mainly two subtypes of MC, lymphocytic or collagenous colitis. Despite the fact that the incidence in MC has been rising over the last decades, research has been sparse and our knowledge about MC remains limited. Specialists in the field have initiated the European Microscopic Colitis Group (EMCG) with the primary goal to create awareness on MC. The EMCG is furthermore a forum with the intention to promote clinical and basic research. In this article statements and comments are given that all members of the EMCG have considered being of importance for a better understanding of MC. The paper focuses on the newest updates in epidemiology, symptoms and diagnostic criteria, pathophysiology and highlights some unsolved problems. Moreover, a new treatment algorithm is proposed on the basis of new evidence from well-designed, randomized control trials.
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| 7. |
- Walter, Susanna, et al.
(författare)
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Anorectal function in patients with collagenous colitis in active and clinically quiescent phase, in comparison with healthy controls
- 2010
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Ingår i: Neurogastroenterology and Motility. - : Blackwell Publishing Ltd. - 1350-1925 .- 1365-2982. ; 22:5, s. 534-
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Tidskriftsartikel (refereegranskat)abstract
- Background Collagenous colitis (CC) is characterized by chronic watery diarrhea, a macroscopically normal colonic mucosa but typical microscopic inflammation. Chronic mucosal inflammation of the colon and rectum has earlier been associated with altered visceral sensitivity, but anorectal function has never been reported in cases of CC. Methods Fifteen patients with CC in active phase recorded their symptoms. The severity of inflammation was determined in mucosal biopsies. Anorectal function was assessed and compared with that of 15 healthy volunteers of corresponding age and matched for gender. After 6 weeks of budesonide treatment when the patients were in clinical remission anorectal function was re-assessed. Key Results All patients had inflammation also in rectum. Patients in active phase had, during rectal balloon distension a higher rectal sensory threshold for the feeling of first sensation, compared with controls (P = 0.02). There were no differences in rectal sensory threshold for the feeling of urgency or maximum distension, between patients with CC in active phase and healthy controls. Rectal volume at first sensation was significantly greater in patients than in controls (P = 0.02), but there were no differences at urgency or maximum distension. Twelve of 15 patients completed 6 weeks of budesonide treatment and all went into clinical remission. No differences in anorectal function were measured when patients had active disease, compared with clinical remission. Conclusions andamp; Inferences Collagenous colitis was not associated with rectal hypersensitivity or disturbed anal function despite rectal inflammation. On the contrary, the sensation threshold for light rectal pressure was elevated in patients with active CC.
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