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Ström, Magnus
Publications (10 of 58) Show all publications
Yakymenko, O., Schoultz, I., Gullberg, E., Ström, M., Almer, S., Wallon, C., . . . Söderholm, J. D. (2018). Infliximab restores colonic barrier to adherent-invasive E. coli in Crohn's disease via effects on epithelial lipid rafts. Scandinavian Journal of Gastroenterology, 53(6), 677-684
Open this publication in new window or tab >>Infliximab restores colonic barrier to adherent-invasive E. coli in Crohn's disease via effects on epithelial lipid rafts
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2018 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, no 6, p. 677-684Article in journal (Refereed) Published
Abstract [en]

Objective: Infliximab is important in the therapeutic arsenal of Crohn’s disease (CD). However, its effect on mucosal barrier function is not fully understood. Adherent-invasive Escherichia coli (AIEC) are important in CD pathophysiology, but the transmucosal uptake routes are partly unknown. We investigated effects of infliximab on uptake of colon-specific AIEC HM427 across CD colonic mucosa.

Materials and methods: Endoscopic biopsies from non-inflamed colon of seven patients with CD, before and after two infliximab infusions, and eight non-inflammation controls, were mounted in Ussing chambers. Paracellular permeability (51Cr-EDTA) and transmucosal passage of GFP-expressing HM427 were studied. Mechanisms of HM427 transepithelial transport were investigated in Caco-2 monolayers treated with TNF, in the presence of infliximab and/or endocytosis inhibitors.

Results: Before infliximab treatment, colonic passage of HM427 [CD: 2475 CFU (450–3000); controls 1163(225–1950)] and 51Cr-EDTA permeability were increased in CD (p < .05), but were restored to control levels by infliximab (CD: 150 (18.8–1069)). In TNF-exposed Caco-2 monolayers HM427 transport and lipid rafts/HM427 co-localization was decreased by infliximab. The lipid raft inhibitor methyl-β-cyclodextrin decreased HM427 transport.

Conclusion: Infliximab restored the colonic barrier to AIEC in CD; an effect partially mediated by blocking lipid rafts in epithelial cells. This ability likely contributes to infliximab’s clinical efficacy in colonic CD.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
Keywords
Inflammatory bowel disease, microbiology, large intestine, intestinal barrier function, adherent invasive E. coli
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-147615 (URN)10.1080/00365521.2018.1458146 (DOI)000438146900008 ()29688802 (PubMedID)
Note

Funding agencies: Swedish Research Council-Medicine [VR-MH 2014-02537]; ALF Grants Region Ostergotland

Available from: 2018-04-27 Created: 2018-04-27 Last updated: 2019-04-30Bibliographically approved
Münch, A., Bohr, J., Miehlke, S., Benoni, C., Olesen, M., Ost, A., . . . Ström, M. (2016). Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial. Gut, 65(1), 47-56
Open this publication in new window or tab >>Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial
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2016 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 65, no 1, p. 47-56Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis.

DESIGN: A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase.

RESULTS: Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious.

CONCLUSIONS: Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation.

TRIAL REGISTRATION NUMBERS: http://www.clinicaltrials.gov (NCT01278082) and http://www.clinicaltrialsregister.eu (EudraCT: 2007-001315-31).

Place, publisher, year, edition, pages
B M J Group, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-112705 (URN)10.1136/gutjnl-2014-308363 (DOI)000366400500010 ()25425655 (PubMedID)
Note

Funding agencies: Dr Falk Pharma GmbH, Freiburg, Germany

Available from: 2014-12-08 Created: 2014-12-08 Last updated: 2017-05-03
Münch, A., Tysk, C., Bohr, J., Madisch, A., Bonderup, O. K., Mohrbacher, R., . . . Miehlke, S. (2016). Smoking Status Influences Clinical Outcome in Collagenous Colitis.. Journal of Crohn's & Colitis, 10(4), 449-454
Open this publication in new window or tab >>Smoking Status Influences Clinical Outcome in Collagenous Colitis.
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2016 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 4, p. 449-454Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The relationship between clinical and histological parameters in collagenous colitis (CC) is poorly understood. Smoking is a risk factor for CC, whereas its impact on clinical activity and outcome is not well known.

METHODS: In a post hoc analysis of pooled data from two randomized controlled trials we assessed the association between demographic data (gender, age, smoking habits, family history of inflammatory bowel disease), clinical variables (duration of symptoms, mean number of stools/watery stools per day, abdominal pain, clinical remission) and histological data (thickness of the collagen band, inflammation of the lamina propria, total numbers of intraepithelial lymphocytes, degeneration). Moreover, we analysed the predictive value of baseline parameters for clinical outcome in a logistic regression model.

RESULTS: Pooled data were available from 202 patients with active CC, of whom 36% were current smokers, 29% former smokers and 35% non-smokers. Smoking status was associated with decreased ability to achieve clinical remission (current smokers vs non-smokers: odds ratio [OR] 0.31, 95% confidence interval [CI] 0.10-0.98, p = 0.045; former smokers vs non-smokers: OR 0.19, 95% CI 0.05-0.73, p = 0.016). Current smokers had an increased mean number of watery stools at baseline compared with non-smokers (p = 0.051) and increased mean number of watery stools per se was associated with decreased likelihood of obtaining clinical remission (OR 0.63, 95% CI 0.47-0.86, p = 0.003). Patient characteristics and histology at baseline had no association with clinical parameters and no predictive value for clinical outcome.

CONCLUSION: Smoking worsens clinical symptoms in CC and is associated with an increased number of watery stools and decreased likelihood of achieving clinical remission. There is no significant association between histology and clinical data.

Place, publisher, year, edition, pages
Oxford University Press, 2016
Keywords
Collagenous colitis; histology; predictive factors; smoking
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-125950 (URN)10.1093/ecco-jcc/jjv235 (DOI)000374262300011 ()26721941 (PubMedID)
Note

Funding agencies: Dr Falk Pharma

Available from: 2016-03-09 Created: 2016-03-09 Last updated: 2017-11-30
Gerdin, L., Eriksson, A. S., Olaison, G., Sjödahl, R., Ström, M., Söderholm, J. D. & Myrelid, P. (2016). The Swedish Crohn Trial: A Prematurely Terminated Randomized Controlled Trial of Thiopurines or Open Surgery for Primary Treatment of Ileocaecal Crohns Disease. Journal of Crohn's & Colitis, 10(1), 50-54
Open this publication in new window or tab >>The Swedish Crohn Trial: A Prematurely Terminated Randomized Controlled Trial of Thiopurines or Open Surgery for Primary Treatment of Ileocaecal Crohns Disease
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2016 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 1, p. 50-54Article in journal (Refereed) Published
Abstract [en]

Background and aims: The importance of efficient and safe treatment of Crohns disease is highlighted by its chronicity. Both medical and surgical treatments have shown good results in the symptomatic control of limited ileocaecal Crohns disease. The aim of this study was to compare medical treatment with surgical treatment of ileocaecal Crohns disease. Methods: Thirty-six patients from seven hospitals with primary ileocaecal Crohns disease were randomized to either medical or surgical treatment. The medical treatment was induction of remission with budesonide and thereafter maintenance treatment with azathioprine. The surgical treatment was open ileocaecal resection. Crohns disease activity index over time, expressed as area under the curve at 1, 3 and 5 years, was the primary endpoint. Subjective health measured with the 36-item Short Form Survey Instrument (SF36) and a visual analogue scale (VAS) were secondary endpoints. Results: There were no differences between the treatment groups in Crohns disease activity index over time. General health, measured as SF36 score, was higher in patients receiving surgical treatment than in those receiving medical treatment at 1 year, but there was no corresponding difference in VAS. Due to the slow inclusion rate and changes in clinical practice, the study was t = erminated prematurely. Conclusion: The study ended up being underpowered and should be interpreted with caution, but there was no clinically significant difference between the two treatment arms. Further studies are needed to address this important clinical question.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2016
Keywords
Surgery; clinical trials; quality of life; socio-economical and psychological endpoints
National Category
Clinical Medicine Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-126143 (URN)10.1093/ecco-jcc/jjv184 (DOI)000370275900010 ()26507858 (PubMedID)
Available from: 2016-03-15 Created: 2016-03-15 Last updated: 2018-03-21
Lowén, M. B. O., Mayer, E., Tillisch, K., Labus, J., Naliboff, B., Lundberg, P., . . . Walter, S. (2015). Deficient habituation to repeated rectal distensions in irritable bowel syndrome patients with visceral hypersensitivity. Neurogastroenterology and Motility, 27(5), 646-655
Open this publication in new window or tab >>Deficient habituation to repeated rectal distensions in irritable bowel syndrome patients with visceral hypersensitivity
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2015 (English)In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 27, no 5, p. 646-655Article in journal (Refereed) Published
Abstract [en]

Background Irritable bowel syndrome (IBS) patients show evidence of altered central processing of visceral signals. One of the proposed alterations in sensory processing is an altered engagement of endogenous pain modulation mechanisms. The aim was to test the hypothesis that IBS patients with (IBS-S) and without visceral hypersensitivity (IBS-N) differ in their ability to engage endogenous pain modulation mechanism during habituation to repeated visceral stimuli.

Methods Brain blood oxygen level dependent (BOLD) response was measured during repeated rectal distension and its anticipation in 33 IBS patients with and without visceral hypersensitivity and 18 healthy controls (HCs). BOLD response to early and late phase of the distension series was compared within and between groups.

Key Results While BOLD response was similar during the early phase of the experiment, IBS-S showed greater BOLD response than IBS-N and HCs during the late phase of the distension series. IBS-S showed increasing BOLD response both to the anticipation and delivery of low intensity rectal distensions in brain regions including insula, anterior and mid cingulate cortex. IBS-N showed decreasing BOLD response to repeated rectal distensions in brain regions including insula, prefrontal cortex and amygdala.

Conclusions & Inferences These findings are consistent with compromised ability of IBS-S to respond to repeated delivery of rectal stimuli, both in terms of sensitization of sensory pathways and habituation of emotional arousal. The fact that both IBS subgroups met Rome criteria, and did not differ in terms of reported symptom severity demonstrates that similar symptom patterns can result from different underlying neurobiological mechanisms.

Keywords
irritable bowel syndrome, brain-gut interaction, fMRI, visceral sensitivity
National Category
Gastroenterology and Hepatology Neurosciences
Identifiers
urn:nbn:se:liu:diva-122143 (URN)10.1111/nmo.12537 (DOI)000364742000007 ()25777251 (PubMedID)
Note

Funding agencies: County Council of Ostergotland, Sweden; National Institute of Health [DK 64531]

Available from: 2015-10-20 Created: 2015-10-20 Last updated: 2018-01-11Bibliographically approved
Daferera, N., Kumar Kumawat, A., Hultgren-Hornquist, E., Ignatova, S., Ström, M. & Münch, A. (2015). Fecal stream diversion and mucosal cytokine levels in collagenous colitis: A case report. World Journal of Gastroenterology, 21(19), 6065-6071
Open this publication in new window or tab >>Fecal stream diversion and mucosal cytokine levels in collagenous colitis: A case report
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2015 (English)In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 19, p. 6065-6071Article in journal (Refereed) Published
Abstract [en]

In this case report, we examined the levels of cytokines expressed before and during fecal stream diversion and after intestinal continuity was restored in a patient with collagenous colitis. We report the case of a 46-year-old woman with chronic, active collagenous colitis who either failed to achieve clinical remission or experienced adverse effects with the following drugs: loperamide, cholestyramine, budesonide, methotrexate and adalimumab. Due to the intractable nature of the disease and because the patient was having up to 15 watery bowel movements per day, she underwent a temporary ileostomy. Colonic biopsies were analyzed for mucosal cytokine protein levels before and during fecal stream diversion and after intestinal continuity was restored. Mucosal protein levels of interleukin (IL)-1 beta, IL-2, IL-6, IL-12, IL-17 A, IL-23, TNF, IFN-gamma, IL-4, IL-5, IL-10 and IL-13 were all higher during active disease and decreased to non-detectable or considerably lower levels during fecal stream diversion. One month after the restoration of bowel continuity, when the patient experienced a relapse of symptoms, IL-2, IL-23 and IL-21 levels were again increased. Our results indicate that fecal stream diversion in this patient suppressed the levels of all cytokines analyzed in colonic biopsies. With the recurrence of clinical symptoms and histological changes after bowel reconstruction, the levels of primarily proinflammatory cytokines increased. Our findings support the hypothesis that a luminal factor triggers the inflammation observed in collagenous colitis.

Place, publisher, year, edition, pages
Baishideng Publishing Group Co. Limited, 2015
Keywords
Microscopic colitis; Collagenous colitis; Luminex; Mucosal cytokines; Fecal stream diversion
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-119587 (URN)10.3748/wjg.v21.i19.6065 (DOI)000355115600036 ()26019474 (PubMedID)
Note

Funding Agencies|Abbott; dr Falk Pharma

Available from: 2015-06-23 Created: 2015-06-22 Last updated: 2018-11-28
Vigren, L., Tysk, C., Ström, M., Kilander, A. F., Hjortswang, H., Bohr, J., . . . Sjoberg, K. (2013). Celiac disease and other autoimmune diseases in patients with collagenous colitis. Scandinavian Journal of Gastroenterology, 48(8), 944-950
Open this publication in new window or tab >>Celiac disease and other autoimmune diseases in patients with collagenous colitis
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2013 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 48, no 8, p. 944-950Article in journal (Refereed) Published
Abstract [en]

Background and aims. Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. Methods. Patients with CC answered questionnaires about demographic data and disease activity. The patients files were scrutinized for information about autoimmune diseases. Results. A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjogrens syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. Conclusion. Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.

Place, publisher, year, edition, pages
Informa Healthcare, 2013
Keywords
autoimmune disease; celiac disease; collagenous colitis; inflammatory bowel disease; microscopic colitis; thyroid disease
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-103409 (URN)10.3109/00365521.2013.805809 (DOI)000322850500007 ()
Available from: 2014-01-20 Created: 2014-01-20 Last updated: 2017-12-06
Lowén, M., Mayer, E. A., Sjoberg, M., Tillisch, K., Naliboff, B., Labus, J., . . . Walter, S. (2013). Effect of hypnotherapy and educational intervention on brain response to visceral stimulus in the irritable bowel syndrome. Alimentary Pharmacology and Therapeutics, 37(12), 1184-1197
Open this publication in new window or tab >>Effect of hypnotherapy and educational intervention on brain response to visceral stimulus in the irritable bowel syndrome
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2013 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 37, no 12, p. 1184-1197Article in journal (Refereed) Published
Abstract [en]

Background Gut-directed hypnotherapy can reduce IBS symptoms, but the mechanisms underlying this therapeutic effect remain unknown. Aim To determine the effect of hypnotherapy and educational intervention on brain responses to cued rectal distensions in IBS patients. Methods Forty-four women with moderate-to-severe IBS and 20 healthy controls (HCs) were included. Blood oxygen level dependent (BOLD) signals were measured by functional Magnetic Resonance Imaging (fMRI) during expectation and delivery of high- (45mmHg) and low-intensity (15mmHg) rectal distensions. Twenty-five patients were assigned to hypnotherapy (HYP) and 16 to educational intervention (EDU). Thirty-one patients completed treatments and posttreatment fMRI. Results Similar symptom reduction was achieved in both groups. Clinically successful treatment (all responders) was associated with significant BOLD attenuation during high-intensity distension in the dorsal and ventral anterior insula (cluster size 142, P=0.006, and cluster size 101, P=0.005 respectively). Moreover HYP responders demonstrated a prepost treatment BOLD attenuation in posterior insula (cluster sizes 59, P=0.05) while EDU responders had a BOLD attenuation in prefrontal cortex (cluster size 60, P=0.05). Prepost differences for expectation conditions were almost exclusively seen in the HYP group. Following treatment, the brain response to distension was similar to that observed in HCs, suggesting that the treatment had a normalising effect on the central processing abnormality of visceral signals in IBS. Conclusions The abnormal processing and enhanced perception of visceral stimuli in IBS can be normalised by psychological interventions. Symptom improvement in the treatment groups may be mediated by different brain mechanisms. Clinical trial number: NCT01815164.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-94599 (URN)10.1111/apt.12319 (DOI)000319295100006 ()
Note

Funding Agencies|County Council of Ostergotland||Lions forskningsfond for folksjukdomar||Svenska Lakaresallskapets forskningsfond||NIDDK|DK048351|

Available from: 2013-06-27 Created: 2013-06-27 Last updated: 2019-02-11
Bednarska, O., Ignatova, S., Dahle, C. & Ström, M. (2013). Intraepithelial lymphocyte distribution differs between the bulb and the second part of duodenum. BMC Gastroenterology, 13
Open this publication in new window or tab >>Intraepithelial lymphocyte distribution differs between the bulb and the second part of duodenum
2013 (English)In: BMC Gastroenterology, ISSN 1471-230X, E-ISSN 1471-230X, Vol. 13Article in journal (Refereed) Published
Abstract [en]

Background

Evaluation of intraepithelial duodenal lymphocytosis (IDL) is important in celiac disease (CD). There is no established cut-off value for increased number of IELs in the bulb.

We therefore investigated the relation between IEL counts in the bulb and duodenal specimens in non-celiac subjects.

Methods

The number of CD3+ IELs was determined in specimens from the second part of the duodenum and from the bulb in 34 non-celiac subjects. The numbers of IELs in the villus tip and sides were counted and the quotient tip/side was calculated. HLA DQ2/DQ8 and serum antibodies against transglutaminase were analysed.

Results

The mean number of IELs per 100 enterocytes (95% CI) in specimens was 14.7 (11.8-17.6) in the bulb, and 21.2 (17.0-25.5) in the second part of the duodenum (p<0.01). There was no difference in IEL count or distribution comparing patients carrying or lacking HLA DQ2/DQ8.

Conclusions

IEL count in non-celiac, HLA DQ2/DQ8 positive or negative patients is significantly lower in the bulb than in the second part of the duodenum. These findings implicate that the site of biopsy should be taken into account when considering duodenal lymphocytosis.

Place, publisher, year, edition, pages
BioMed Central, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-96711 (URN)10.1186/1471-230X-13-111 (DOI)000322132500001 ()
Note

Funding Agencies|Medical Research Council of Southeast Sweden||

Available from: 2013-08-23 Created: 2013-08-23 Last updated: 2017-12-06
Münch, A., Ignatova, S. & Ström, M. (2012). Adalimumab in budesonide and methotrexate refractory collagenous colitis. Scandinavian Journal of Gastroenterology, 47(1), 59-63
Open this publication in new window or tab >>Adalimumab in budesonide and methotrexate refractory collagenous colitis
2012 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, ISSN 0036-5521, Vol. 47, no 1, p. 59-63Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
Informa Healthcare, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-73436 (URN)10.3109/00365521.2011.639079 (DOI)000298190400008 ()
Available from: 2012-01-03 Created: 2012-01-03 Last updated: 2017-12-08
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