| 1. |
- Bjornsson, Einar, et al.
(författare)
-
Akut leversvikt - viktigt med snabb multidisciplinär handläggning
- 2007
-
Ingår i: Läkartidningen. - 0023-7205. ; 104:4, s. 210-213
-
Tidskriftsartikel (refereegranskat)abstract
- A recent study in Sweden on patients with acute liver failure (ALF) 1994-2003 demonstrated that the most common causes were paracetamol toxicity (42%) and idiosyncratic drug reactions (15%). In 11% of cases of ALF no definite etiology could be established. Among patients with paracetamol toxicity, the spontaneous survival without liver transplantation was 82% compared to 49% in patients with reactions to other drugs and 29% among the patients with indeterminate cause. Patients with ALF need a rapid and effective diagnostic work-up to detect the etiology as this often determines the outcome. In ALF it is of major importance to make an early contact with a transplant centre as the search for a suitable donor organ may take time in patients who are candidates for a liver transplantation. Patients with acute liver failure need a multidisciplinary care with co-operation between hepatologists, intensive care unit specialists and transplant surgeons.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Björnsson, Einar, et al.
(författare)
-
Akut leversvikt - viktigt med snabb multidisciplinär handläggning : [Acute liver failure--rapid multidisciplinary management]
- 2007
-
Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 104:4, s. 210-213
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- A recent study in Sweden on patients with acute liver failure (ALF) 1994-2003 demonstrated that the most common causes were paracetamol toxicity (42%) and idiosyncratic drug reactions (15%). In 11% of cases of ALF no definite etiology could be established. Among patients with paracetamol toxicity, the spontaneous survival without liver transplantation was 82% compared to 49% in patients with reactions to other drugs and 29% among the patients with indeterminate cause. Patients with ALF need a rapid and effective diagnostic work-up to detect the etiology as this often determines the outcome. In ALF it is of major importance to make an early contact with a transplant centre as the search for a suitable donor organ may take time in patients who are candidates for a liver transplantation. Patients with acute liver failure need a multidisciplinary care with co-operation between hepatologists, intensive care unit specialists and transplant surgeons.
|
|
| 5. |
- Elmberg, Maria, et al.
(författare)
-
Increased Mortality Risk in Patients With Phenotypic Hereditary Hemochromatosis But Not in Their First-Degree Relatives
- 2009
-
Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 137:4, s. 1301-1309
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Hereditary hemochromatosis (HH) is an autosomal-recessive disorder characterized by iron overload. Relatives of HH patients were screened and those with HH-associated mutations and an increased iron load were identified. However, little is known about their mortality or strategies for their management. We assessed mortality among Swedish patients with HH and their first-degree relatives using health and census registers. METHODS: We performed a matched population-based cohort study of 3832 patients with HH and their 14,496 first-degree relatives using data collected from 1990 through 2007. Mortality data from these groups were compared with that of 38,969 population controls and their 143,349 first-degree relatives using Cox regression analyses. RESULTS: Patients identified on the basis of hospitalization with HH had an increased risk (relative risk [RR]) for death (RR, 2.45; 95% confidence interval [CI], 2.27-2.64; 857 deaths). Patients identified through other means had a mortality risk that was lower than those identified in the hospital but higher than controls (RR, 1.15; 95% CI, 1.00-1.33; 216 deaths). Their first-degree relatives had only a marginally increased mortality risk (RR, 1.05; 95% CI, 1.01-1.10); this RR was similar to that of patients' spouses (RR, 1.09; 95% CI, 0.86-1.38; 82 deaths). Patients with HH who also had a family history of HH did not have an increased mortality risk compared with other groups (RR, 1.05; 95% CI 0.67-1.62; 21 deaths). CONCLUSIONS: Patients with HH have a modestly increased mortality risk compared with controls. The mortality of relatives is increased marginally compared with controls, and is similar among biological and nonbiological relatives.
|
|
| 6. |
- Rajani, Rupesh, et al.
(författare)
-
Budd-Chiari syndrome in Sweden : epidemiology, clinical characteristics and survival - an 18-year experience
- 2009
-
Ingår i: Liver international (Print). - Oxford : Blackwell Munksgaard. - 1478-3223 .- 1478-3231. ; 29:2, s. 253-259
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The exact incidence and prevalence of Budd-Chiari syndrome (BCS) is unknown in the general population. Published reports differ in terms of the clinical characteristics, effects of therapy and survival. AIMS: To investigate the epidemiology, clinical presentation and survival in patients with BCS. METHODS: Retrospective multicentre study in Sweden reviewing the medical records of all patients with BCS 1986-2003, identified from the computerised diagnosis database of 11 hospitals, including all university hospitals and liver transplantation centres. RESULTS: Forty-three patients with BCS were identified, of whom nine (21%) had concomitant portal vein thrombosis. The mean age-standardised incidence and prevalence rates in 1990-2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. Myeloproliferative disorders (38%), thrombophilic factors (31%) and oral contraceptives (30%) were common aetiological factors. Two or more risk factors were present in 44%. In 23%, no risk factor was evident. The median follow-up time was 2.7 years. Seventy-two percent were on anticoagulant therapy during follow-up. Transjugular intrahepatic portosystemic shunting, surgical shunting procedures and liver transplantation were performed in 4, 6 and 18 patients respectively. Nineteen patients died. The overall transplantation-free survival at 1, 5 and 10 years was 47, 28 and 17% respectively. CONCLUSIONS: Budd-Chiari syndrome is a rare disorder; the mean age-standardised incidence and prevalence rates in Sweden in 1990-2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. The presence of a myeloproliferative disorder was a common aetiological factor in our cohort and about half of the patients had a multifactorial aetiology. The transplantation-free survival was poor.
|
|
| 7. |
- Wallerstedt, Sven, 1944, et al.
(författare)
-
Abdominal tenderness in ascites patients indicates spontaneous bacterial peritonitis
- 2007
-
Ingår i: European journal of internal medicine. - : Elsevier BV. - 0953-6205 .- 1879-0828. ; 18:1, s. 44-47
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Spontaneous bacterial peritonitis (SBP), which has been reported to be present in 10-30% of patients with cirrhotic ascites, may easily be overlooked. An important aim of our study was to determine whether there are any clinical signs which, in clinical practice, may predict or exclude SBP. Methods: We studied 133 patients with cirrhotic ascites from medical units at nine Swedish university hospitals where there had been at least one diagnostic ascites tap with analysis of polymorphonuclear leukocytes in the ascites fluid. The patients had initially been questioned about background factors and physically examined according to a standardized case record form. Samples of blood, urine, and ascites were then drawn for analysis according to a structured schedule. Results: SBP could be excluded in 80% of all the cases and was confirmed in 8% of the 133 patients in the final analysis. Abdominal pain and abdominal tenderness were more common in patients with SBP (p < 0.01), but no other physical sign or laboratory test could separate SBP cases from the others. Conclusions: SBP was present in about one-tenth of the hospitalized patients with cirrhotic ascites in this cohort. Performing repeated physical examinations and paying particular attention to abdominal tenderness may be the best way to become aware of the possible development of this complication.
|
|
| 8. |
- Werner, Mårten, et al.
(författare)
-
Autoimmune hepatitis among fertile women : strategies during pregnancy and breastfeeding?
- 2007
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 42:8, s. 986-991
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. In published studies there is a lack of data about the risks, management and how women with autoimmune hepatitis (AIH) decide on and are advised about pregnancy. The aim of this study was to investigate how women with AIH consider pregnancies, are advised and pharmacologically treated, as well as the outcome. Material and methods. A questionnaire was mailed to 128 women with AIH diagnosed during their fertile period and data from the Swedish National Birth Register was also used for matched controls. Results. There was an 83% response rate to the questionnaires. Sixty-three pregnancies were reported by 35 women. 48% did not consult their doctors before getting pregnant. More than half of the women reduced or stopped the immune suppression during pregnancy or breastfeeding. Some women were advised to abstain from pregnancy or even to have an abortion. Caesarean sections were performed more frequently in the AIH group (16% compared with 6.5% in the control group p<0.01).There were no significant differences in the number of stillborn infants or infants with malformations. However, 30% of the patients experienced flare-up after delivery. Conclusions. In general, the outcome of pregnancy in women with AIH seems to be good. Current pharmacological treatment appears to be safe, including azathioprine during pregnancy and lactation. After delivery an active preparedness to increase pharmacotherapy should be considered.
|
|
| 9. |
- Werner, Mårten, et al.
(författare)
-
Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: A nationwide study
- 2008
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 43:10, s. 1232-1240
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. Autoimmune hepatitis (AIH) is a chronic liver disease, which if untreated can lead to cirrhosis and hepatic failure. The aim of the study was to investigate the incidence, prevalence, diagnostic tradition and clinical initial presentation of AIH. Material and methods. Analyses were performed in 473 patients identified as having probable or definite AIH. Results. The incidence of AIH was 0.85/100,000 (95% CI 0.69-1.01) inhabitants, which is somewhat lower than reported previously. The point prevalence amounted to 10.7/100,000 (95% CI 8.8-13.1), and 76% of the cases were females. The age-related incidence curve was bimodal but men were found to have only one incidence peak in the late teens, whereas women had a peak after menopause. AIH was presented as a spectrum of clinical settings from detected en passant to acute liver failure. Almost 30% of patients already had liver cirrhosis at diagnosis. Autoantibodies indicative of AIH type 1 were found in 79% of cases. Other concomitant autoimmune diseases were frequently found (49%). Conclusions. The incidence and prevalence figures confirm that AIH is a fairly uncommon disease in the Swedish population. Symptoms at presentation were unspecific, but almost half of the patients were jaundiced, with around 30% having liver cirrhosis. The majority of Swedish AIH patients had AIH type 1.
|
|
| 10. |
- Werner, Mårten, et al.
(författare)
-
Hepatic and extrahepatic malignancies in autoimmune hepatitis. A long-term follow-up in 473 Swedish patients
- 2009
-
Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 50:2, s. 388-393
-
Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Autoimmune Hepatitis (AIH) is a liver disease which may lead to liver cirrhosis. Cirrhosis is a well-known risk factor for hepatocellular cancer. Lymphoma is a disease, where immune modulating drugs as well as the autoimmune disease itself may contribute to the elevated risk. The aim was to investigate the risks of malignancies in a large cohort of AIH patients. Methods: Four hundred and seventy-three patients with AIH were matched to the Swedish national cancer register as well as to the death cause register. Results: We found an overall higher risk of malignancies in the cohort of A I H patients from the date of diagnosis with a SIR of 1.51 (95% CI 1.10-2.03). SIR in the subpopulation of well defined catchment areas and complete case finding was 23.28 (95% CI 7.5-54.34) for HCC. Lymphomas were found a SIR of 13.09 (95% CI 4.22-30.56). Conclusions: There was an overall increased risk of malignancies in a cohort of AIH patients, which manly was caused by hepatobiliary cancers. However, the true risk of HCC in an AIH cirrhotic cohort has yet to be investigated. A significantly higher risk of lymphomas was also found, but no clear cut association to the use of immune modulators.
|
|
| 11. |
- Almer, Sven, et al.
(författare)
-
6-Thioguanine therapy in Crohns disease-Observational data in Swedish patients
- 2009
-
Ingår i: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658 .- 1878-3562. ; 41:3, s. 194-200
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Adverse events (AE) leading to discontinuation or dose-reduction of thiopurine therapy (TP) occur in 9-28% of patients with inflammatory bowel disease. 6-Thioguanine (6-TG) has been proposed as an alternative treatment in patients intolerant for azathioprine (AZA), but some concerns have been raised about drug safety. Methods: We evaluated in a prospective manner the tolerance and efficacy of 6-TG in 23 Crohns disease (CD) patients (13 men, median age 41 (19-65) years) with prior intolerance (n = 18) or resistance (It = 5) to AZA and/or 6-mercaptopurine (6-MP). In addition, eight patients had tried mycophenolate mofetil. Seventeen patients (74%) had undergone intestinal resection, often several times. Results: Patients were treated with a median daily dose of 40 mg 6-TG (range 20-60) for 259 (15-2272) days. Seven of 13 patients (54%) with active disease went into remission after 8 (4-26) weeks. Sixteen patients (70%) experienced AE that lead to discontinuation (n=10) after 85 (15-451) days or dose reduction (n=6) after 78 (10-853) days. Ten of 18 patients (56%) with prior TP-intolerance discontinued 6-TG treatment due to AE compared to none of five patients with TP-resistance (p=0.046). Of 13 patients that tolerated 6-TG, eight discontinued the drug due to therapeutic failure (n=5) or safety concerns (n=3). Eight patients (35%) continued treatment beyond 12 months. There was no significant difference in maximum thioguanine nucleotide levels between patients with AE leading to discontinuation/dose reduction and patients without AE, 652 (99-2488) vs. 551 (392-1574) pmol/8 x 10(8) RBC; p=0.80. Conclusions: In this cohort of CD patients with severe disease failing traditional thiopurine treatment, a small fraction (22%) had long-term benefit of 6-TG-treatment. 6-TG therapy seems to offer a limited therapeutic gain for patients intolerant to both AZA and 6-MP and other treatment options should be considered.
|
|
| 12. |
|
|
| 13. |
- Almer, Sven, 1953-, et al.
(författare)
-
Leukocyte scintigraphy compared to intraoperative small bowel enteroscopy and laparotomy findings in Crohn's disease
- 2007
-
Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998 .- 1536-4844. ; 13:2, s. 164-174
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Leukocyte scintigraphy is a noninvasive investigation to assess inflammation. We evaluated the utility of labeled leukocytes to detect small bowel inflammation and disease complications in Crohn's disease and compared it to whole small bowel enteroscopy and laparotomy findings.Methods: Scintigraphy with technetium-99m exametazime-labeled leukocytes was prospectively performed in 48 patients with Crohn's disease a few days before laparotomy; 41 also had an intraoperative small bowel enteroscopy. The same procedures were performed in 8 control patients. Independent grading of scans was compared with the results of enteroscopy and with surgical, histopathologic, and clinical data.Results: In the 8 control patients leukocyte scan, endoscopy, and histopathology were all negative for the small bowel. In patients with Crohn's disease and small bowel inflammation seen at enteroscopy and/or laparotomy (n = 39) the scan was positive in 33. In 8 patients without macroscopic small bowel inflammation, the scan was positive for the small bowel in 3 patients; at histology, 2 of 3 had inflammation. When combining results for patients and controls, the sensitivity of leukocyte scan for macroscopically evident small bowel inflammation was 0.85, specificity 0.81, accuracy 0.84, positive predictive value 0.92, and negative predictive value 0.68. Scintigraphy detected inflammatory lesions not known before laparotomy in 16 of 47 (34%) Crohn's disease patients and showed uptake in 25 of 35 (71%) bowel strictures. It was diagnostic regarding 4 of 8 abscesses and 9 of 15 fistulas. In 6 patients (13%) lesions first demonstrated by leukocyte scintigraphy were treated during the surgery performed.Conclusions: Leukocyte scintigraphy reliably detects small bowel inflammation in Crohn's disease. It gives additional information on the presence of inflammatory lesions in a fraction of patients planned for surgery.
|
|
| 14. |
|
|
| 15. |
- Almer, Sven, et al.
(författare)
-
Modern läkemedelsterapi vid crohn - Nationella riktlinjer
- 2009
-
Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 106:45, s. 2988-2993
-
Tidskriftsartikel (refereegranskat)abstract
- Lättanvända begrepp och definitioner på sjukdomsaktivitet och behandlingseffekt bör få ökad spridning inom sjukvården.Majoriteten av patienter med Crohns sjukdom behöver långvarig läkemedelsbehandling, och ungefär hälften genomgår en eller flera operationer någon gång under sjukdomstiden.Det är viktigt att tidigt i sjukdomsförloppet identifiera riskfaktorer för utveckling av komplicerad och aggressiv sjukdom och behandla intensivt i dessa fall.En aktiv strategi med regelbundet övervägande av tillgängliga behandlingsalternativ medför att de flesta patienter med Crohns sjukdom behåller en god livskvalitet.
|
|
| 16. |
- Bergquist, Annika, et al.
(författare)
-
Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis
- 2008
-
Ingår i: Clinical Gastroenterology and Hepatology. - New York : Elsevier. - 1542-3565 .- 1542-7714. ; 6:8, s. 939-943
-
Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC. Methods: Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register. Results: The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6–84.4), 11.1 (3.3–37.8), and 2.3 (0.9–6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3–4.9) and for Crohn's disease 1.4 (0.8–2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9–18.9). Conclusions: First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC.
|
|
| 17. |
|
|
| 18. |
- de Boer, NKH, et al.
(författare)
-
6-thioguanine treatment in inflammatory bowel disease : A critical appraisal by a European 6-TG working party
- 2006
-
Ingår i: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 73:1, s. 25-31
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity. Copyright (c) 2006 S. Karger AG, Basel.
|
|
| 19. |
- Fransson, Martin, 1978-, et al.
(författare)
-
A preliminary study of modeling and simulation in individualized drug dosage – azathioprine on inflammatory bowel disease
- 2007
-
Ingår i: SIMS 2006: Proceedings of the 47th Conference on Simulation and Modelling, Helsinki, Finland. - Helsinki : Kopio Niini Oy. - 9525183300 ; , s. 216-220
-
Konferensbidrag (refereegranskat)abstract
- Individualized drug dosage based on population pharmacokinetic/dynamic models is an important future technology used to reduce or eliminate side effects of certain drugs, e.g. cancer drugs. In this paper we report preliminary results from work-in-progress: a simplified linear model of the metabolism of a cancer treatment drug was estimated from experimental data. The model was then validated against the same data as a test of the adequacy of the model structure. From this investigation it became apparent that the model structure could not be used due to its inability to recreate the dynamic properties of the system.
|
|
| 20. |
- Haglund, Sofie, 1975-, et al.
(författare)
-
IMPDH activity in thiopurine-treated patients with inflammatory bowel disease - Relation to TPMT activity and metabolite concentrations
- 2008
-
Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 65:1, s. 69-77
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: Azathioprine and 6-mercaptopurine are steroid-sparing drugs used in inflammatory bowel disease (IBD). The polymorphic enzyme thiopurine S-methyltransferase (TPMT) is of importance for thiopurine metabolism and occurrence of adverse events. The role of other thiopurine-metabolizing enzymes is less well known. This study investigated the role of inosine-5′- monophosphate dehydrogenase (IMPDH), which is a key enzyme in the de novo synthesis of guanine nucleotides and also strategically positioned in the metabolic pathway of thiopurines. METHODS: IMPDH was measured in 100 healthy blood donors. IMPDH, TPMT and metabolite concentrations were studied in 50 patients with IBD on stable thiopurine therapy. IMPDH activity was measured in peripheral blood mononuclear cells. TPMT activity, 6-methylthioinosine 5′-monophosphate (meTIMP) and 6-thioguanine nucleotide (6-TGN) concentrations were measured in red blod cells, which is the current practice in clinical monitoring of thiopurines. Enzyme activities were related to metabolite concentrations and clinical characteristics. RESULTS: A wide range of IMPDH activity was observed both in healthy blood donors (median 13.1, range 4.7-24.2 nmol mg-1 protein h-1) and IBD patients (median 14.0, range 7.0-21.7). There was a negative correlation between IMPDH activity and dose-normalized meTIMP concentrations (rs = -0.31, P = 0.03), but no evident correlation to 6-TGN concentration or the meTIMP/6-TGN ratio. There were no significant correlations between TPMT activity and metabolite concentrations. CONCLUSION: Even though the meTIMP concentrations correlated inversely to the IMPDH activity, the role of IMPDH in balancing the formation of methylated and phosphorylated metabolites was not evident. Taken together, the results give cause to question established opinions about thiopurine metabolism. © 2007 The Authors.
|
|
| 21. |
- Haglund, Sofie, 1975-, et al.
(författare)
-
Pharmacotranscriptomics in thiopurine treated IBD patients with different metabolite profiles
- 2008
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Thiopurine drugs are used to induce and maintain remission in inflammatory bowel disease. The methyl thioinosine monophosphate (meTIMP)/6-thioguanine nucleotide (6-TGN) concentration ratio has been related to drug response and adverse reactions. Here we investigated for differences in gene expression levels between patients with different metabolite profiles. Methods: Transcriptional profiles in blood samples from an exploratory patient cohort (n=21) comprising three groups; patients with normal thiopurine S-methyltransferase phenotype and meTIMP/6-TGN concentration ratio >20, ratio 10.0-14.0 and ratio ≤4, respectively, were assessed by hybridization to microarrays. Results were further evaluated with reverse transcription qPCR [exploratory and a validation cohort of patients (n=33)]. Additionally, known genes of the thiopurine metabolic pathway were analysed separately. Results: The whole genome expression analysis did not identify any significant differences between metabolite profiles. Analysis of thiopurine related genes revealed a large interindividual variation in gene expression, but only small differences between metabolite profiles. Three clusters of co-regulated genes were defined based on correlations between gene expression levels. The concentration of meTIMP correlated to the expression of NT5E (rs = 0.33, P = 0.02) and TPMT (rs = - 0.37, P = 0.007). The concentration of 6-TGN correlated to the expression of HPRT1 (rs = - 0.31, P = 0.03) and SLC29A1 (rs = 0.33, P = 0.02). With the exception of SLC29A1, these genes belonged to the same cluster of genes. Conclusions: Our results illustrates the complexity of the thiopurine metabolism and suggest that differences between metabolite profiles are explained either by interactions between several genes, each with a small contribution, or at the post-transcriptional level. Search for more precise tools in order to explain differences in metabolite profiles is needed.
|
|
| 22. |
- Hindorf, Ulf, et al.
(författare)
-
Adverse events leading to modification of therapy in a large cohort of patients with inflammatory bowel disease
- 2006
-
Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 24:2, s. 331-342
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Adverse events leading to discontinuation or dose reduction of thiopurine therapy occur in 9-28% of patients with inflammatory bowel disease. Aims: To evaluate the influence of thiopurine methyltransferase status and thiopurine metabolites in a large patient population for the risk of developing adverse event. Methods: Three hundred and sixty-four patients with inflammatory bowel disease and present or previous thiopurine therapy were identified from a local database. Results: The adverse event observed in 124 patients (34%) were more common in adults than children (40% vs. 15%, P < 0.001) and in low to intermediate (≤9.0 U/mL red blood cell) than normal thiopurine methyltransferase activity (P = 0.02). Myelotoxicity developed later than other types of adverse event. An increased frequency of adverse event was observed in patients with tioguanine (thioguanine) nucleotide above 400 or methylated thioinosine monophosphate above 11 450 pmol/ 8 × 108 red blood cell. A shift to mercaptopurine was successful in 48% of azathioprine-intolerant patients and in all cases of azathioprine-induced myalgia or arthralgia. Conclusions: A pre-treatment determination of thiopurine methyltransferase status might be appropriate as patients with low to intermediate thiopurine methyltransferase activity are more prone to develop an adverse event, determination of metabolite levels can be useful in the case of an adverse event. Mercaptopurine therapy should be considered in azathioprine-intolerant patients. © 2006 The Authors.
|
|
| 23. |
|
|
| 24. |
- Hindorf, Ulf, et al.
(författare)
-
Mercaptopurine treatment should be considered in azathioprine intolerant patients with inflammatory bowel disease
- 2009
-
Ingår i: Alimentary Pharmacology & Therapeutics. - : Wiley. - 1365-2036 .- 0269-2813. ; 29:6, s. 654-61
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Adverse drug reactions are a significant reason for therapeutic failure during thiopurine treatment of inflammatory bowel disease. Some smaller series in this patient population have shown that a switch to mercaptopurine may be successful in many cases of azathioprine intolerance. AIM: To assess the long-term outcome of mercaptopurine treatment in a large patient population with azathioprine intolerance. METHODS: We identified 135 patients (74 women; median age 40 years) with Crohn's disease (n = 88) or ulcerative colitis (n = 47) and reviewed their medical records. RESULTS: A total of 70 patients (52%) tolerated mercaptopurine and were followed up for 736 (362-1080) days; 65 patients discontinued mercaptopurine due to adverse events after 25 (8-92) days. Mercaptopurine was tolerated in 71% (12/17) with hepatotoxicity and in 68% (13/19) with arthralgia/myalgia during azathioprine treatment. Previous abdominal surgery was more common in mercaptopurine intolerant patients [39/65 (60%) vs. 27/70 (39%); P = 0.02] and thiopurine methyltransferase activity was higher in mercaptopurine tolerant patients than in mercaptopurine intolerant patients [13.2 (11.4-15.3) vs. 11.8 (9.6-14.2) U/mL red blood cells; P = 0.04; n = 81]. CONCLUSIONS: A trial of mercaptopurine should be considered in azathioprine intolerance, as half of the patients tolerate a switch to mercaptopurine. Patients with hepatotoxicity or arthralgia/myalgia during azathioprine treatment might benefit more often than those with other types of adverse events.
|
|
| 25. |
- Hindorf, Ulf, et al.
(författare)
-
Pharmacogenetics during standardised initiation of thiopurine therapy in inflammatory bowel disease.
- 2006
-
Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 55:10, s. 1423-1431
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Firm recommendations about the way thiopurine drugs are introduced and the use of thiopurine methyltransferase (TPMT) and metabolite measurements during treatment in inflammatory bowel disease (IBD) are lacking. Aim: To evaluate pharmacokinetics and tolerance after initiation of thiopurine treatment with a fixed dosing schedule in patients with IBD. Patients: 60 consecutive patients with Crohn's disease (n = 33) or ulcerative colitis (n = 27) were included in a 20 week open, prospective study. Methods: Thiopurine treatment was introduced using a predefined dose escalation schedule, reaching a daily target dose at week 3 of 2.5 mg azathioprine or 1.25 mg 6-mercaptopurine per kg body weight. TPMT and ITPA genotypes, TPMT activity, TPMT gene expression, and thiopurine metabolites were determined. Clinical outcome and occurrence of adverse events were monitored. Results: 27 patients completed the study per protocol, while 33 were withdrawn (early protocol violation (n = 5), TPMT deficiency (n = 1), thiopurine related adverse events (n = 27)); 67% of patients with adverse events tolerated long term treatment on a lower dose (median 1.32 mg azathioprine/kg body weight). TPMT activity did not change during the 20 week course of the study but a significant decrease in TPMT gene expression was found (TPMT/huCYC ratio; p = 0.02). Patients with meTIMP concentrations > 11 450 pmol/8 x 10(8) red blood cells during steady state at week 5 had an increased risk of developing myelotoxicity (odds ratio = 45.0; p = 0.015). Conclusions: After initiation of thiopurine treatment using a fixed dosing schedule, no general induction of TPMT enzyme activity occurred, though TPMT gene expression decreased. The development of different types of toxicity was unpredictable, but we found that measurement of meTIMP early in the steady state phase helped to identify patients at risk of developing myelotoxicity.
|
|
| 26. |
- Hindorf, Ulf, et al.
(författare)
-
Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease
- 2006
-
Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 55:10, s. 1423-1431
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Firm recommendations about the way thiopurine drugs are introduced and the use of thiopurine methyltransferase (TPMT) and metabolite measurements during treatment in inflammatory bowel disease (IBD) are lacking. Aim: To evaluate pharmacokinetics and tolerance after initiation of thiopurine treatment with a fixed dosing schedule in patients with IBD. Patients: 60 consecutive patients with Crohn's disease (n = 33) or ulcerative colitis (n = 27) were included in a 20 week open, prospective study. Methods: Thiopurine treatment was introduced using a predefined dose escalation schedule, reaching a daily target dose at week 3 of 2.5 mg azathioprine or 1.25 mg 6-mercaptopurine per kg body weight. TPMT and ITPA genotypes, TPMT activity, TPMT gene expression, and thiopurine metabolites were determined. Clinical outcome and occurrence of adverse events were monitored. Results: 27 patients completed the study per protocol, while 33 were withdrawn (early protocol violation (n = 5), TPMT deficiency (n = 1), thiopurine related adverse events (n = 27)), 67% of patients with adverse events tolerated long term treatment on a lower dose (median 1.32 mg azathioprine/kg body weight). TPMT activity did not change during the 20 week course of the study but a significant decrease in TPMT gene expression was found (TPMT/huCYC ratio, p = 0.02). Patients with meTIMP concentrations > 11 450 pmol/8 × 108 red blood cells during steady state at week 5 had an increased risk of developing myelotoxicity (odds ratio = 45.0, p = 0.015). Conclusions: After initiation of thiopurine treatment using a fixed dosing schedule, no general induction of TPMT enzyme activity occurred, though TPMT gene expression decreased. The development of different types of toxicity was unpredictable, but we found that measurement of meTIMP early in the steady state phase helped to identify patients at risk of developing myelotoxicity.
|
|
| 27. |
- Hjortswang, Henrik, et al.
(författare)
-
The Short Health Scale : a valid measure of subjective health in ulcerative colitis
- 2006
-
Ingår i: Scandinavian Journal of Gastroenterology. - Oslo : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:10, s. 1196-1203
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. Assessment of health-related quality of life (HRQOL) is important in both clinical practice and clinical trials, and several multi-item questionnaires are currently in use. We have devised and evaluated a simplified four-item questionnaire, the Short Health Scale (SHS), representing each of four health dimensions: (a) symptom burden, (b) social function, (c) disease-related worry and (d) general well-being.Material and methods. Three hundred patients with ulcerative colitis completed the SHS and three other HRQOL questionnaires (IBDQ, RFIPC and PGWB). Half of the patients repeated the questionnaires after 6 months – or earlier if disease activity changed. Test–retest reliability was derived from measurements of the SHS questions, 2 weeks apart, on 18 patients in remission.Results. Patients in relapse scored higher on each of the four SHS questions than patients in remission (p < 0.001). Each of the four SHS scores were associated with results of their corresponding health dimension obtained with the other three questionnaires (rs=0.57–0.78, p < 0.001) (validity). The results of the SHS proved stable on repeated measurement with a 2-week interval in patients in remission (rs=0.71–0.91, p < 0.01) (test–retest reliability). Patients with a change in disease activity had a significant change in their SHS scores (p < 0.05) (responsiveness).Conclusions. The SHS is a valid, reliable and responsive measure of subjective health in patients with ulcerative colitis. It is simple to administer, quickly completed and the results do not need further calculations. The SHS can be used in clinical trials and in clinical practice to identify the patient's main problems affecting health.
|
|
| 28. |
- Lindgren, Stefan, et al.
(författare)
-
Transitions between variant forms of primary biliary cirrhosis during long-term follow-up
- 2009
-
Ingår i: EUROPEAN JOURNAL OF INTERNAL MEDICINE. - : Elsevier BV. - 0953-6205 .- 1879-0828. ; 20:4, s. 398-402
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Conditions exhibiting features of two different autoimmune liver diseases are designated overlap syndromes. Variant forms display some, but not all, characteristics of a distinct autoimmune liver disease. We describe transitions over time between variant forms of PBC, i.e. AMA-negative PBC, autoimmune hepatitis (AIH)-PBC overlap and autoimmune cholangitis (AIC) in a large cohort of PBC patients in Sweden. Methods: We retrieved all patients with variant forms of PBC in six university hospitals in Sweden, covering 60% of the Swedish population. The diagnosis of PBC and its variants was based on laboratory findings and compatible histological features. The revised autoimmune hepatitis scoring system proposed by the International Autoimmune Hepatitis Group was used to establish the diagnosis of AIH. Results: In a population of 800 patients with PBC, we identified 35 (5%) variant forms; 25 patients with AIH-PBC overlap, 8 with AIC and 2 with AMA-negative PBC at the time of our study. The initial diagnoses were PBC (3 patients), AIH (3), AIH-PBC overlap (16), AIC (8) and AMA-negative PBC with (1) or without (4) concomitant AIH. The median follow-up was 125 (41-360) months. Immunosuppression and ursodeoxycholic acid induced a complete or good regression of increased aminotransferases in about half of the patients who were given one or both of these treatments. Conclusions: Variant forms of PBC are seen in approximately 5% of PBC patients in Sweden. Transition between different forms may occur, emphasizing the value of repeat biopsies, but established overlapping AIH-PBC seems to be stable over time.
|
|
| 29. |
- Lindqvist Appell, Malin, 1976-, et al.
(författare)
-
Explaining TPMT genotype/phenotype discrepancy by haplotyping of TPMT*3A and identification of a novel sequence variant, TPMT*23
- 2007
-
Ingår i: Pharmacogenetics and Genomics. - 1744-6872. ; 17:10, s. 891-895
-
Tidskriftsartikel (refereegranskat)abstract
- Thiopurine methyltransferase (TPMT) is a polymorphic enzyme involved in the metabolism of thiopurine drugs. Owing to polymorphisms in the TPMT gene (TPMT*2-*22), the enzyme activity varies interindividually. Patients with reduced TPMT activity may develop adverse reactions when treated with standard doses of thiopurines. This work focuses on a TPMT genotype/phenotype discrepancy found in a patient during routine testing. The patient displayed very low TPMT enzyme activity and she was genotyped by pyrosequencing as being heterozygous for the 460G>A and 719A>G polymorphisms (TPMT*3A). Complete sequencing in combination with haplotyping of the TPMT gene revealed a novel sequence variant, 500C>G, on one allele and TPMT*3A on the other allele, giving rise to the novel genotype TPMT*3A/*23. When investigating the patient's relatives, they too had the TPMT*3A/*23 genotype in combination with low enzyme activity. We conclude that this novel variant allele affects enzyme activity, as the individuals carrying it had almost undetectable TPMT activity. © 2007 Lippincott Williams & Wilkins, Inc.
|
|
| 30. |
- Lindqvist Appell, Malin, 1976-, et al.
(författare)
-
No induction of thiopurine methyltransferase during thiopurine treatment in inflammatory bowel disease
- 2006
-
Ingår i: Nucleosides, Nucleotides & Nucleic Acids. - : Informa UK Limited. - 1525-7770 .- 1532-2335. ; 25:9-11, s. 1033-1037
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to follow, during standardized initiation of thiopurine treatment, thiopurine methyltransferase (TPMT) gene expression and enzyme activity and thiopurine metabolite concentrations, and to study the role of TPMT and ITPA 94C > A polymorphisms for the development of adverse drug reactions. Sixty patients with ulcerative colitis or Crohn's disease were included in this open and prospective multi-center study. Thiopurine naive patients were prescribed azathioprine (AZA), patients previously intolerant to AZA received 6-mercaptopurine (6-MP). The patients followed a predetermined dose escalation schedule, reaching target dose at Week 3; 2.5 and 1.25 mg/kg body weight for AZA and 6-MP, respectively. The patients were followed every week during Weeks 1-8 from baseline and then every 4 weeks until 20 weeks. TPMT activity and thiopurine metabolites were determined in erythrocytes, TPMT and ITPA genotypes, and TPMT gene expression were determined in whole blood. One homozygous TPMT-deficient patient was excluded. Five non compliant patients were withdrawn during the first weeks. Twenty-seven patients completed the study per protocol; 27 patients were withdrawn because of adverse events. Sixty-seven percent of the withdrawn patients tolerated thiopurines at a lower dose at Week 20. There was no difference in baseline TPMT enzyme activity between individuals completing the study and those withdrawn for adverse events (p = 0.45). A significant decrease in TPMT gene expression (TPMT/huCYC ratio, p = 0.02) was found, however TPMT enzyme activity did not change. TPMT heterozygous individuals had a lower probability of remaining in the study on the predetermined dose (p = 0.039). The ITPA 94C > A polymorphism was not predictive of adverse events (p = 0.35).
|
|
| 31. |
|
|
| 32. |
- Lindqvist Appell, Malin, 1976-, et al.
(författare)
-
Thiopurines in inflammatory bowel disease - The role of pharmacogenetics and therapeutic drug monitoring
- 2006
-
Ingår i: Current Pharmacogenomics. - : Bentham Science Publishers Ltd.. - 1570-1603. ; 4:4, s. 285-300
-
Tidskriftsartikel (refereegranskat)abstract
- Pharmacogenetics represents the study of variability in drug response due to genetic variations. Inflammatory bowel disease (IBD, i.e. primarily Crohn's disease and ulcerative colitis) is characterized by a chronic or relapsing inflammation of the digestive tract. The thiopurines 6-mercaptopurine (6-MP) and azathioprine (AZA), an imidazol derivative and pro-drug of 6-MP, are widely used in IBD, particularly in Crohn's disease. The metabolism of thiopurines is complex and individually variable. Thiopurine methyltransferase (TPMT) is a key enzyme in this metabolism and exhibits a genetic variability due to a number of variant alleles coding for a defective enzyme. The formation of biologically active thioguanine nucleotides (TGN) and methylated metabolites may vary considerably due to the TPMT activity. Patients with decreased TPMT activity are at increased risk of developing severe side effects if treated with conventional thiopurine doses, due to the accumulation of toxic metabolites. Determination of the TPMT phenotype or genotype is often used to identify individuals with increased risk for adverse events. Twenty-one variant TPMT alleles have been described, of which three are more common than the others. An association between inosine triphosphate pyrophosphatase polymorphisms and adverse events during thiopurine treatment has also been proposed. In this review, the clinical value of TPMT status determination and pharmacological monitoring of thiopurine metabolites are discussed as well as the increased interest in the use of 6-thioguanine, a thiopurine with a less complex metabolism, as an alternative for patients who do not tolerate AZA or 6-MP. It can be concluded that TPMT determination before start of thiopurine therapy is of value to identify individuals with increased risk for adverse reactions due to genetic enzyme deficiency. However, large prospective studies are still needed to evaluate the true benefit of monitoring thiopurine metabolites during thiopurine treatment. © 2006 Bentham Science Publishers Ltd.
|
|
| 33. |
- Mesterton, Johan, et al.
(författare)
-
Resource Use and Societal Costs for Crohn's Disease in Sweden
- 2009
-
Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1536-4844 .- 1078-0998. ; 15:12, s. 1882-1890
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The usual onset of Crohn's disease (CD) is between 15 and 30 years of age, thus affecting people during their most economically productive period in life. Methods: This study intended to estimate societal costs and health-related quality of life (HRQoL) in Swedish patients in different stages of CD. Cross-sectional data on disease activity (measured with the Harvey-Bradshaw Index [HBI]), direct medical resource use, work productivity, and HRQoL (assessed using the 15D instrument) were collected for 420 patients by questionnaires to patients, to the treating physician, and from medical records. Based on HBI, current treatment, and response to treatment, patients were classified into the following disease states: Remission, Response, Active, Refractory, and Surgery. Results: The average 4-week cost per patient in 2007 was estimated at (sic)721 (USD 988), of which 64% was due to lost productivity. The total 4-week cost of care was (sic)255 (USD 349) in Remission, (sic)831 (USD 1138) in Response, (sic)891 (USD 1220) in Active, (sic)1360 (USD 1864) in Refractory, and (sic)16984 (USD 23269) in Surgery. HBI was the most important predictor of costs of care-a 1-point increase in HBI increased total costs by 25% (P < 0.001). HRQoL differed between the disease states: 0.92 in Remission, 0.90 in Response, 0.82 in Active, 0.81 in Refractory, and 0.77 in Surgery. Conclusions: Patients in remission have the lowest costs and the highest HRQoL. Patients responding to treatment have lower costs of care than patients with high disease activity who are not treated or do not respond to treatment:. Thus, total costs of care might be reduced by efficient treatment.
|
|
| 34. |
- Myrelid, Pär, 1970-, et al.
(författare)
-
Azathioprine as a postoperative prophylaxis reduces symptoms in aggressive Crohn's disease
- 2006
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:10, s. 1190-1195
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. Recurrence of Crohn's disease (CD) after surgery is common. Azathioprine/6-mercaptopurine (Aza/6-MP) is effective in controlling medically induced remission but, so far, has only been sparsely investigated after surgically induced remission. This study comprises a subset of CD patients considered to have an aggressive disease course and chosen for treatment with Aza postoperatively. Material and methods. In 1989-2000, a total of 100 patients with CD were given Aza/6-MP as a postoperative prophylaxis. Fourteen Aza/6-MP-intolerant patients were compared with 28 Aza-tolerant patients, matched for gender, age, and duration of disease. Patients were prospectively registered for symptoms using a modified Crohn's disease activity index (CDAI) and perceived health was assessed on a visual analogue scale (VAS). The primary outcome variable was the modified CDAI postoperatively integrated over time, other variables were time to first relapse (modified CDAI ≥ 150), time to first repeated surgery, number of courses of steroids, and repeated surgery per year of follow-up. Patients were followed for a median of 84.7months (23.2-140). Results. The modified CDAI integrated over time was 93 for Aza-treated patients compared with 184 for controls (p = 0.01) and time to first relapse was 53 and 24 months, respectively (p < 0.05). Aza-treated patients needed fewer courses of corticosteroids (p = 0.05) compared with controls. Perceived health did not differ between the groups, nor did need of repeated surgery. Time to first repeat operation was 53 and 37 months, respectively. Conclusions. In CD patients considered to have an aggressive disease course, Aza reduced symptoms after surgery and prolonged the time to symptomatic relapse. The findings support a role for Aza as a postoperative maintenance treatment in CD. © 2006 Taylor & Francis.
|
|
| 35. |
- Myrelid, Pär, et al.
(författare)
-
Thiopurine Therapy Is Associated with Postoperative Intra-Abdominal Septic Complications in Abdominal Surgery for Crohns Disease
- 2009
-
Ingår i: Diseases of the Colon & Rectum. - 0012-3706 .- 1530-0358. ; 52:8, s. 1387-1394
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Thiopurines are important as maintenance therapy in Crohns disease, but there have been concerns whether thiopurines increase the risk for anastomotic complications. The present study was performed to assess whether thiopurines alone, or together with other possible risk factors, are associated with postoperative intra-abdominal septic complications after abdominal surgery for Crohns disease. METHODS: Prospectively registered data regarding perioperative factors were collected at a single tertiary referral center from 1989 to 2002. Data from 343 consecutive abdominal operations on patients with Crohns disease were entered into a multivariate analysis to evaluate risk factors for intra-abdominal septic complications. All operations involved either anastomoses, strictureplasties, or both; no operations, however, involved proximal diversion. RESULTS: Intra-abdominal septic complications occurred in 26 of 343 operations (8%). Thiopurine therapy was associated with an increased risk of intra-abdominal septic complications (16% with therapy; 6% without therapy; P = 0.044). Together with established risk factors such as pre-operative intra-abdominal sepsis (18% with sepsis; 6% without sepsis; P = 0.024) and colocolonic anastomosis (16% with such anastomosis; 6% with other types of anastomosis; P = 0.031), thiopurine therapy was associated with intra-abdominal septic complications in 24% if any 2 or all 3 risk factors were present compared with 13% if any 1 factor was present, and only 4% in patients if none of these factors were present (P andlt; 0.0001). CONCLUSIONS: Thiopurine therapy is associated with postoperative intra-abdominal septic complications. The risk for intra-abdominal septic complications was related to the number of identified risk factors. This increased risk should be taken into consideration when planning surgery for Crohns disease.
|
|
| 36. |
- Nayeri, Fariba, 1958-, et al.
(författare)
-
Hepatocyte growth factor (HGF) in fecal samples : rapid detection by surface plasmon resonance
- 2005
-
Ingår i: BMC Gastroenterology. - 1471-230X. ; 5:13
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe development of biosensors, based on surface plasmon resonance (SPR) technology, enables monitoring of a variety of biospecific interactions without the need for chemical-, biological- or radiological-labelled reagents.MethodWe utilised SPR to detect hepatocyte growth factor (HGF) in reconstituted faecal samples and studied samples from patients with infectious gastroenteritis (n = 20) and normal controls (n = 10). Mouse anti-human HGF monoclonal antibodies and recombinant human HGF receptor (c-Met)/Fc chimera were immobilised in flow cells of a CM5 biosensor chip.ResultsWe found that infectious gastroenteritis produced a higher signal response compared to controls, due to binding of HGF to monoclonal anti-HGF antibody as well as binding of HGF to c-Met receptor (p < 0.01). The SPR signal response correlated with results from ELISA (r = 72%, p > 0.001). The signal response decreased significantly (p < 0.05) when samples were diluted with dextran, because of reduction in both specific as well as unspecific binding of HGF to dextran. The decrease in the specific response might imply that the dextran- binding site for HGF overlaps with the antibody binding epitope, or that dextran binding induces a conformational change of the HGF molecule. Bands corresponding to HGF were found by gel electrophoresis of purified faeces in an affinity chromatography column immobilised by HGF ligands.ConclusionDetermination of HGF by SPR might be beneficial in diagnosis of acute situations that present with symptoms of gastroenteritis and may, possibly, guide appropriate medical treatments. This is to our knowledge the first report on the use of SPR for detection of HGF in faeces samples.
|
|
| 37. |
- Norén, Bengt, 1955-, et al.
(författare)
-
Absolute quantification of human liver metabolite concentrations by localized in vivo 31P NMR spectroscopy in diffuse liver disease
- 2005
-
Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 15:1, s. 148-157
-
Tidskriftsartikel (refereegranskat)abstract
- Phosphorus-31 NMR spectroscopy using slice selection (DRESS) was used to investigate the absolute concentrations of metabolites in the human liver. Absolute concentrations provide more specific biochemical information compared to spectrum integral ratios. Nine patients with histopathologically proven diffuse liver disease and 12 healthy individuals were examined in a 1.5-T MR scanner (GE Signa LX Echospeed plus). The metabolite concentration quantification procedures included: (1) determination of optimal depth for the in vivo measurements, (2) mapping the detection coil characteristics, (3) calculation of selected slice and liver volume ratios using simple segmentation procedures and (4) spectral analysis in the time domain. The patients had significantly lower concentrations of phosphodiesters (PDE), 6.3±3.9 mM, and ATP-β, 3.6±1.1 mM, (P<0.05) compared with the control group (10.0±4.2 mM and 4.2±0.3 mM, respectively). The concentrations of phosphomonoesters (PME) were higher in the patient group, although this was not significant. Constructing an anabolic charge (AC) based on absolute concentrations, [PME]/([PME] + [PDE]), the patients had a significantly larger AC than the control subjects, 0.29 vs. 0.16 (P<0.005). Absolute concentration measurements of phosphorus metabolites in the liver are feasible using a slice selective sequence, and the technique demonstrates significant differences between patients and healthy subjects.
|
|
| 38. |
- Norén, Bengt, 1955-, et al.
(författare)
-
Separation of advanced from mild fibrosis in diffuse liver disease using 31P magnetic resonance spectroscopy
- 2008
-
Ingår i: European Journal of Radiology. - : Elsevier. - 0720-048X .- 1872-7727. ; 66:2, s. 313-320
-
Tidskriftsartikel (refereegranskat)abstract
- 31P-MRS using DRESS was used to compare absolute liver metabolite concentrations (PME, Pi, PDE, γATP, αATP, βATP) in two distinct groups of patients with chronic diffuse liver disorders, one group with steatosis (NAFLD) and none to moderate inflammation (n = 13), and one group with severe fibrosis or cirrhosis (n = 16). All patients underwent liver biopsy and extensive biochemical evaluation. A control group (n = 13) was also included. Absolute concentrations and the anabolic charge, AC = {PME}/({PME} + {PDE}), were calculated.Comparing the control and cirrhosis groups, lower concentrations of PDE (p = 0.025) and a higher AC (p < 0.001) were found in the cirrhosis group. Also compared to the NAFLD group, the cirrhosis group had lower concentrations of PDE (p = 0.01) and a higher AC (p = 0.009). No significant differences were found between the control and NAFLD group. When the MRS findings were related to the fibrosis stage obtained at biopsy, there were significant differences in PDE between stage F0–1 and stage F4 and in AC between stage F0–1 and stage F2–3.Using a PDE concentration of 10.5 mM as a cut-off value to discriminate between mild, F0–2, and advanced, F3–4, fibrosis the sensitivity and specificity were 81% and 69%, respectively. An AC cut-off value of 0.27 showed a sensitivity of 93% and a specificity of 54%.In conclusion, the results suggest that PDE is a marker of liver fibrosis, and that AC is a potentially clinically useful parameter in discriminating mild fibrosis from advanced.
|
|
| 39. |
- Nyblom, Helena, 1968, et al.
(författare)
-
The AST/ALT ratio as an indicator of cirrhosis in patients with PBC.
- 2006
-
Ingår i: Liver international : official journal of the International Association for the Study of the Liver. - : Wiley. - 1478-3223 .- 1478-3231. ; 26:7, s. 840-5
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: A non-invasive, simple and non-expensive test to predict cirrhosis would be highly desirable. The aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio has been proven to be such an indicator of cirrhosis in alcoholic liver disease, hepatitis C. AIM: To test whether the AST/ALT ratio is a marker of cirrhosis also in patients with primary biliary cirrhosis (PBC). METHODS: The study consisted of 160 patients. In 126 patients, we had clinical and laboratory data at the time of diagnosis and follow-up with outcome: liver-related death, liver transplantation and survival. In 121 patients, we had laboratory data and liver histology. RESULTS: We found that the AST/ALT ratio was significantly higher in cirrhotic patients than in non-cirrhotic patients. A high AST/ALT ratio was significantly associated with esophageal varices and ascites. In a multivariate analysis, bilirubin and ALP were predictors of poor prognosis. CONCLUSION: The AST/ALT ratio seems to be of clinical value as a hint to the diagnosis of cirrhosis in patients with PBC but not as a prognostic factor.
|
|
| 40. |
- Olsson, Rolf, et al.
(författare)
-
High prevalence of small duct primary sclerosing cholangitis among patients with overlapping autoimmune hepatitis and primary sclerosing cholangitis
- 2009
-
Ingår i: EUROPEAN JOURNAL OF INTERNAL MEDICINE. - : Elsevier BV. - 0953-6205 .- 1879-0828. ; 20:2, s. 190-196
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Overlap syndrome is a term used for overlapping features of autoimmune hepatitis and primary sclerosing cholangitis or primary biliary cirrhosis and for autoimmune cholangitis. We describe a high prevalence of small duct primary sclerosing cholangitis among patients with overlapping autoimmune hepatitis and primary sclerosing cholangitis. Methods: We sought to retrieve all patients with overlap syndrome between primary sclerosing cholangitis and autoimmune hepatitis in six university hospitals in Sweden. The revised autoimmune hepatitis scoring system proposed by the International Autoimmune Hepatitis Group was used to establish the diagnosis autoimmune hepatitis. Endoscopic retrograde cholangiography and/or magnetic resonance cholangiography were used to separate the primary sclerosing cholangitis cases diagnosed through liver biopsy into small and large primary sclerosing cholangitis. A histologocial diagnosis compatible with both autoimmune hepatitis and primary sclerosing cholangitis was required for inclusion. Results: 26 patients fulfilled our criteria for histological overlap of autoimmune hepatitis and primary sclerosing cholangitis, 7 (27%) of which had small duct primary sclerosing cholangitis. The reliability of the diagnosis small duct primary sclerosing cholangitis was supported by a very close similarity between small and large duct primary sclerosing cholangitis patients in clinical and laboratory data, and by a poor response to immunosuppressive therapy in the small duct primary sclerosing cholangitis patients. Patients with large duct overlap syndrome had a good response to immunosuppressive therapy. In both groups, our limited experience from ursodeoxycholic acid was largely poor. Conclusions: Small duct primary sclerosing cholangitis is prevalent in the overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis.
|
|
| 41. |
- Prytz, Hanne, et al.
(författare)
-
Dynamic FDG-PET is useful for detection of cholangiocarcinoma in patients with PSC listed for liver transplantation
- 2006
-
Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 44:6, s. 1572-1580
-
Tidskriftsartikel (refereegranskat)abstract
- Five to 15% of patients with primary sclerosing cholangitis (PSC) develop cholangiocarcinoma (CC) with a median survival of 5 to 7 months, an outcome not significantly improved by liver transplantation. However, if CC is found incidentally during the procedure or in the explanted liver, 5-year survival rates of 35% are reported. A noninvasive method to detect CC small enough to allow for intended curative surgery is needed. Unfortunately, computed tomography (CT) and ultrasonography (US) have poor sensitivity for detection of CC in PSC, however, positron emission tomography (PET) using 2-[ 18F]fluoro-2-deoxy-D-glucose (FDG) differentiates well between CC and nonmalignant tissue. We examined whether PET findings are valid using a blinded study design comparing pretransplantation FDG-PET results with histology of explanted livers. Dynamic FDG-PET was performed in 24 consecutive patients with PSC within 2 weeks after listing for liver transplantation and with no evidence of malignancy on CT, magnetic resonance imaging, or ultrasonography. The PET Center staff was blinded to clinical findings, and surgeons and pathologists were blinded to the PET results. Three patients had CC that was correctly identified by PET. PET was negative in 1 patient with high-grade hilar duct dysplasia. In 20 patients without malignancies, PET was false positive in 1 patient with epitheloid granulomas in the liver. In conclusion, dynamic FDG-PET appears superior to conventional imaging techniques for both detection and exclusion of CC in advanced PSC. FDG-PET may be useful for screening for CC in the pretransplant evaluation of patients with PSC. Copyright © 2006 by the American Association for the Study of Liver Diseases.
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
- Rajani, Rupesh, 1973-, et al.
(författare)
-
Portavenstrombos
- 2007
-
Annan publikation (populärvet., debatt m.m.)abstract
- Portaventrombos (PVT) är ett ovanligt tillstånd. Bakomliggande orsaker är vanligen leversjukdom (framförallt cirros), intraabdominell malignitet samt hyperkoagulabilitet. Två eller flera samtidiga riskfaktorer, oftast en lokal faktor kombinerat med en systemisk, förekommer i mer än hälften av fallen. Man bör ha diagnosen i åtanke vid oklar buksmärta, vid tecken på portal hypertension utan samtidig leversjukdom samt vid plötslig försämring hos en patient med känd leversjukdom. Asymtomatiska patienter är inte ovanliga. Randomiserade behandlingsstudier saknas. Behandlingen inriktas på att reversera och förhindra progression av trombosen samt att förebygga och behandla komplikationer såsom varixblödningar och kolangiopati. Rekanalisering kan ske i upptill 90% av fallen vid tidigt insättande av antikoagulantia. Prognosen är god om patienten inte har cirros, malignitet eller mesenterialventrombos; 1-, 5- och 10-års överlevnad är då på 95%, 89% och 81%.
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
- Stjernman, Henrik, et al.
(författare)
-
Evaluation of the inflammatory bowel disease questionnaire in Swedish patients with Crohn's disease
- 2006
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:8, s. 934-943
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Health-related quality of life (HRQoL) is an important measure of inflammatory bowel disease (IBD) health outcome. The Inflammatory Bowel Disease Questionnaire (IBDQ) comprising 32 items grouped into four dimensions is a widely used IBD-specific HRQoL instrument. The purpose of this study was to evaluate the validity, reliability and responsiveness of the Swedish translation of the IBDQ in patients with Crohn's disease (CD). MATERIAL AND METHODS: Four hundred and forty-eight patients with CD completed the IBDQ and three other HRQoL questionnaires (Rating Form of IBD Patient Concerns; Short Form-36; and the Psychological General Well-Being Index) in connection with their regular visit at the outpatient clinic. Disease activity was assessed by the physician on a 4-point Likert scale. Thirty-two patients who were stable in remission completed the questionnaires a second time, 4 weeks later. A total of 418 patients repeated all measurements after 6 months. RESULTS: The dimensional scores were highly correlated with other measures of corresponding aspects of HRQoL and were significantly better in remission than in relapse. High test-retest correlations indicated good reliability. Responsiveness was confirmed in patients whose disease activity changed over time. However, high correlations between the dimensions, poor correlations between items within each dimension, and factor analysis all indicated that the original grouping of the items is not valid for Swedish CD patients. CONCLUSIONS: Although the Swedish IBDQ has good external validity, reliability and responsiveness for patients with CD, our results did not support the original grouping of the items.
|
|
| 48. |
- Stjernman, Henrik, et al.
(författare)
-
Factors predicting the outcome of disease activity assessment in Crohn's disease
- 2009
-
Ingår i: Inflammatory Bowel Diseases. - : John Wiley & Sons. - 1078-0998 .- 1536-4844. ; 15:12, s. 1859-1866
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Crohn's Disease Activity Index (CDAI) has become the gold standard for assessment of disease activity in CD. This study investigated the relationship between CDAI and the physicians' global assessment of disease activity (PGA) and whether different demographic and disease-related factors predict the outcome.METHODS: Multiple linear regression analysis was used to investigate the relationship between CDAI and PGA obtained from 405 CD patients. Predictors of the CDAI and the PGA outcome were identified.RESULTS: The correlation between CDAI and PGA was moderate. In patients with CDAI >150, 72% of the total score were derived from the subjective variables. The regression coefficients were not significant for 3 of the CDAI variables. In regression analysis, C-reactive protein (CRP), stenosis, smoking, bowel resection, concomitant disease, and gender predicted the CDAI outcome. The PGA outcome was predicted only by CRP, stenosis, and fistula.CONCLUSIONS: The correlation between CDAI and PGA was moderate and the subjective variables had a high impact on CDAI. Factors with no obvious relation to inflammatory activity predicted the outcome of CDAI, but not PGA. In trials of CD therapies, separation of subjective (symptoms, well-being) from objective (endoscopy, inflammatory markers) variables should be considered in the assessment of disease activity.
|
|
| 49. |
- Teml, Alexander, et al.
(författare)
-
A systematic survey evaluating 6-thioguanine-related hepatotoxicity in patients with inflammatory bowel disease
- 2007
-
Ingår i: Wiener Klinische Wochenschrift. - : Springer Science and Business Media LLC. - 0043-5325 .- 1613-7671. ; 119:17-18, s. 519-526
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Drug-induced liver injury was recently reported as a major complication leading to hepatic nodular regenerative hyperplasia (NRH) in patients with inflammatory bowel disease (IBD) and 6-thioguanine (6-TG) therapy. The aim of the study was to evaluate the prevalence of 6-TG-related hepatotoxicity in a large multi-centered IBD population by means of a systematic online survey. METHODS: Clinical and laboratory data, imaging techniques (sonography, CT, MRI) and histology of liver biopsies were surveyed in IBD patients treated with 6-TG. The decision on whether liver imaging and/or liver biopsy were performed was exclusively at the discretion of the investigator. RESULTS: 6-TG use was fully documented in 296 patients (median treatment duration 56 weeks, range < 1-207). Laboratory signs of drug-induced liver injury were found in 43 patients (14.5%). Liver imaging revealed pathologic results in 68/176 patients (38.6%). Liver biopsy was performed in a subset of 60 patients, using silver-reticulin staining (n = 59), NRH was considered in 16 patients (27.1%). Age was the only independent, albeit weak, risk factor for development of NRH. CONCLUSION: This large online survey confirms the strong association between 6-TG treatment and the significant risk of development of NRH in patients with IBD. The definitive diagnosis of NRH depends solely upon liver biopsy. © 2007 Springer-Verlag.
|
|
| 50. |
- Thiébaut, R., et al.
(författare)
-
TNFSF15 polymorphisms are associated with susceptibility to inflammatory bowel disease in a new European cohort
- 2009
-
Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 104:2, s. 384-391
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Inflammatory bowel disease (IBD), e.g., Crohn's disease (CD) and ulcerative colitis (UC), is a complex genetic disorder. Tumor necrosis factor (ligand) superfamily, member 15 (TNFSF15) has been previously identified as a susceptibility gene for CD in Japanese and UK cohorts. This replication study was designed in order to confirm and further validate the role of TNFSF15 in IBD. METHODS: A total of 666 IBD families (corresponding to 2,982 relatives) with European ancestry were genotyped for the rs6478108 and rs7869487 polymorphisms, which define the main TNFSF15 haplotypes previously associated with CD. An association between the main haplotypes and CD, UC and IBD was tested using the Genehunter TDT and Unphased statistics. Caspase recruitment domain 15 (CARD15)/TNFSF15 interaction and genotype/phenotype correlations were also studied. RESULTS: The previously reported "high-risk" haplotype (A) was associated with IBD (P=0.001) (OR=1.25 (1.05-1.50)) and CD (P=0.02) (OR=1.31 (1.03-1.67)) whereas the "protective" (B) haplotype was significantly less transmitted to IBD and CD patients. No interaction between CARD15 and TNFSF15 was detected. We also failed to define a clinical subgroup of CD patients specifically associated with TNFSF15 haplotype A. CONCLUSIONS: This study confirms that TNFSF15 or a closely linked gene is involved in the genetic predisposition to CD.
|
|
