| 1. |
- Englund, Gunilla, et al.
(författare)
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Regional levels of drug transporters along the human intestinal tract : Co-expression of ABC and SLC transporters and comparison with Caco-2 cells
- 2006
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 29:3-4, s. 269-277
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Tidskriftsartikel (refereegranskat)abstract
- A vast number of drugs are subjected to active or facilitated transport and multiple transport mechanism may contribute to the net flux during drug absorption. The main objective of this study was to quantify the regional mRNA expression and determine the co-expression of drug transporters from the ABC (Pgp, BCRP, MRP2, MRP3) and SLC (PEPT1, MCT1, OATPB, OCTN2, OCT1) families along the human intestine (duodenum, jejunum, ileum, and colon). A second objective was to compare the transporter expression between the different intestinal regions and Caco-2 cells. Eight out of nine of the investigated transporters exhibited significant regional differences in expression. OATPB was the only transporter that did not show a region-dependency in the expression along the human intestinal canal. The expression of Pgp, BCRP, OCTN2 and MCT1 differed along the small intestine, but the expression differences were greater than five-fold only for Pgp. The rank order of transcript prevalence was identical in the ileum and the jejunum. Between the ileum and colon, seven transcripts were differentially expressed, and MCT1, OCTN2 and MRP3 were expressed at higher levels in the colon than in the small intestine. The expression of transporters in Caco-2 was closest to the expression pattern in the small intestine, although the expression of OATPB, BCRP and MRP2 differed more than five-fold between the Caco-2 cells and ileum. In conclusion, this study provides quantitative data on the expression of transporters from the ABC and SLC families along the human intestine, which can be useful in the interpretation of clinical studies where more than one intestinal transporter contribute to the net transport and in the computer modelling of drug absorption.
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| 2. |
- Rönnblom, Anders, et al.
(författare)
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Acute severe attacks of ulcerative colitis in a population-based cohort : epidemiology, treatment and outcome
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : TAYLOR & FRANCIS LTD. - 0036-5521 .- 1502-7708. ; 55:5, s. 555-559
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although the criteria for acute severe ulcerative colitis have been stable for decades, the epidemiology for this condition has rarely been described in a population-based setting.Aim: To describe the appearance, treatment and outcome of acute severe ulcerative colitis in a population-based cohort of ulcerative colitis diagnosed between 2005 and 2009.Methods: Between 2005 and 2009, all patients diagnosed with ulcerative colitis in the County of Uppsala, a geographical area consisting of an average 318,000 individuals, were included in a cohort that was followed until the end of 2019. Three hundred and thirty patients covering an age interval of 3-86 years, were included. The medical records of the patients were scrutinized with regard to clinical course, drugs prescribed for IBD, hospitalization and surgical interventions. Patients that had left the health care area were contacted through letters except in case of emigration outside the country.Results: Forty-nine patients experienced a first severe attack (14.8%), and six of these were operated (12.2%). Fifteen patients suffered a second or third attack, and one more was operated. One elderly lady died postoperatively from sepsis. Conclusions: Acute severe attacks of ulcerative colitis appeared early after diagnosis and if surgery was escaped, there was no increased need for surgery in case of a new severe attack later.
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| 3. |
- Rönnblom, Anders, et al.
(författare)
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Clinical course of Crohn's disease during the first 5 years. Results from a population-based cohort in Sweden (ICURE) diagnosed 2005-2009
- 2017
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 52:1, s. 81-86
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the study was to describe the medical treatment, change in phenotype, need for surgery and IBD-associated mortality during the first 5 years after diagnosis. Material and Methods: Patients diagnosed with Crohn's disease including all age groups in the Uppsala healthcare region in the middle of Sweden 2005-2009 were included in the study. Medical notes were scrutinised and patients contacted. Out of 269 patients, 260 (96.3%) could be followed for 5 full years or until death. Results: The following drugs were used: 5-ASA 66.7%, systemic steroids 76.4%, antimetabolites 56.7% and anti-TNF 20.3%. Described with the Montreal classification, the proportion with inflammatory behaviour decreased from 78.1% to 74.0% from diagnosis to end of the observation, patients with stricturing behaviour increased from 13.0% to 15.4% and patients with penetrating behaviour increased from 8.9% to 10.6%. After the first year, 12.4% had been treated with intestinal resection or colectomy, a figure that increased to 14.8 after 5 years. Two patients suffered an IBD-related death. Conclusions: Compared to similar patient cohorts, the present study demonstrates that although the course of Crohn's disease seems difficult to change during the first year after diagnosis, the following years up to 5 years shows a more benign course than has usually been described earlier.
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| 4. |
- Rönnblom, Anders, et al.
(författare)
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Clinical course of Crohn's disease in a population-based cohort in Uppsala County followed for 10 years
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : TAYLOR & FRANCIS LTD. - 0036-5521 .- 1502-7708. ; 55:11, s. 1301-1307
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: There is a shortage of studies describing the outcome of patients with Crohn's disease (CD) where both biological therapy and immunomodulators (IMMs) have been available. The aim of the present study was to describe the clinical course of the disease, the use of drugs, the need for surgery and mortality in a prospectively recruited population-based cohort of patients followed for 10 years.Methods: All patients diagnosed with CD in the County of Uppsala in Sweden 2005-2009 were prospectively recruited and followed until the end of 2019. The medical notes were scrutinised and relevant information collected.Results: One hundred and fifty-four patients covering all age groups were diagnosed with CD and 145 (94.2%) could be followed for 10 years or until death. Nine patients were lost to follow up. The following drugs were used: 5-ASA 83%, steroids 84%, IMMs 69% and biologicals 23%. The proportion of penetrating disease increased from 9.7 to 14.5%. Primary bowel resections were performed in 22% of the patients, and none of these had any secondary surgery because of recurrent or progressive disease during the observation time. Twelve patients (7.8%) died during the follow up, and one of these because of a small bowel carcinoma.Conclusions: In the present study, the clinical course of CD was similar to previous reports during the first year after diagnosis, but the following years were considerably more stable with moderate increase of intestinal damage and totally a low frequency of surgery and no repeated surgery.
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| 5. |
- Rönnblom, Anders, et al.
(författare)
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Complications and adverse effects related to surgical and medical treatment in patients with inflammatory bowel disease in a prospectively recruited population-based cohort
- 2021
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 56:11, s. 1296-1303
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Medical adverse effects and surgical complications have been reported during treatment of patients with inflammatory bowel diseases (IBDs). There is however a shortage of studies describing these in the same cohort of patients.AIM: To describe medical adverse effects and surgical complications in a prospectively followed population-based cohort of patients followed for at least 10 years.METHODS: All newly diagnosed patients with ulcerative colitis (UC) and Crohn's disease (CD) in the county of Uppsala between 2005 and 2009 were prospectively followed. At the end of 2019, the medical notes were scrutinised and all medical adverse effects and postoperative surgical complications were registered.RESULTS: A total of 330 patients with UC and 153 patients with CD in all age groups were included in the cohort. Four hundred and forty-two of these (91.5%) could be followed for 10 years or until death. One hundred and twenty-two patients (26.9%) experienced one or more adverse effects during the pharmacological treatment, and 25 of these could be classified as serious. Fifty-seven malignancies were diagnosed during the observation time. Surgery was performed in 16/330 UC and 33/153 CD patients. Frequency of early postoperative complications was 31% for UC patients and 36% for CD patients. Most complications were minor but two patients were re-operated, two needed intensive care and one patient died postoperatively.CONCLUSIONS: Adverse effects related to medical therapy were experienced by approximately every fourth patient, and by every third patient that was operated.
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| 6. |
- Rönnblom, Anders, et al.
(författare)
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Low colectomy rate five years after diagnosis of ulcerative colitis. Results from a prospective population-based cohort in Sweden (ICURE) diagnosed during 2005-2009*
- 2016
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 51:11, s. 1339-1344
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The medical treatment of ulcerative colitis (UC) has seen a change towards a more active attitude during recent years, including both the use of more traditional drugs as well as new biological substances. In this epidemiological study we have evaluated the results of modern treatment of UC in a population-based cohort of patients including all age groups, with regard to relapse rate, colectomy and IBD-associated mortality.Material and methods: Patients diagnosed with UC in the Uppsala health care region in the middle of Sweden during 2005-2009 were included in the study. Out of 524 patients, 491 (93%) could be followed for five full years or until death.Results: Nineteen patients (3.9%) had died and two of these deaths could be attributed to UC (one postoperative death and one colonic carcinoma). The following drugs were used by the patients during the study period: 5-ASA (91%), systemic steroids (66%), immunomodulators (IMM), mainly thiopurines (26%) and anti-TNF (11%). During the observation period, 74% experienced at least one relapse and 5.3% were subjected to colectomy. Among patients<17 years at diagnosis, colectomy was performed in two (4.8%).Conclusions: Five years after diagnosis of ulcerative colitis, 5.3% had been subjected to colectomy and two patients (0.38%) had died because of the disease.
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| 7. |
- Rönnblom, Anders, et al.
(författare)
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Treatment and outcome of ulcerative colitis during the first 10 years after diagnosis in a prospectively followed population-based cohort
- 2021
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 56:4, s. 403-409
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Tidskriftsartikel (refereegranskat)abstract
- Background and aimsThere is a shortage of studies evaluating the effect of prevalent use of immunomodulators (IMMs) and biologicals on the clinical course of ulcerative colitis (UC) during 10 years. The aim of the present study is to report the use of drugs and surgery as well as mortality in a population based setting.MethodsBetween 2005 and 2009, we identified 330 patients in all ages (3–86 years) with an incident diagnosis of UC in the County of Uppsala, Sweden. They were followed prospectively and the medical notes were retrospectively analysed with special reference to the use of drugs, surgery and mortality.ResultsMedian follow-up was 11.2 years (inter-quartile range 10.2–12.7). Out of the 330 patients, 298 (90.3%) could be followed for at least 10 years or until death. The cumulative exposure to different drugs was as follows: 5-ASA 96.6%, steroids 73.3%, IMMs 35.4% and biologicals 11.4%. Fourteen patients (4.6%) needed a colectomy during the observation time. Overall mortality in 10 years was 7% (23/330) whereof three patients died as a consequence of the disease or its treatment. Three patients (0.9%) were diagnosed with colonic cancer of whom two also had sclerosing cholangitis.ConclusionsA frequent use of IMMs and biologicals during 10 years, can result in a low need for colectomy without increased mortality compared to previous reports.
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