| 1. |
- Berggren, Sofia, et al.
(author)
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Gene and protein expression of P-glycoprotein, MRP1, MRP2 and CYP3A4 in the small and large human intestine
- 2007
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In: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 4:2, s. 252-257
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Journal article (peer-reviewed)abstract
- The cytochrome P450 3A4 enzyme and the ABC-transporters may affect the first-pass extraction and bioavailability of drugs and metabolites. Conflicting reports can be found in the literature on the expression levels of efflux transporters in human intestine and how they vary along the intestine. The relative levels of mRNA and protein of CYP3A4 and the ABC tranporters Pgp (ABCB1), MRP1 (ABCC1), and MRP2 (ABCC2) were determined using RT-PCR and Western blot for human intestinal tissues (n = 14) from jejunum, ileum and colon. The expression of mRNA for CYP3A4, Pgp, and MRP2 was highest in jejunum and decreased toward more distal regions, whereas MRP1 was equally distributed in all intestinal regions. For CYP3A4, a more significant correlation could be established between mRNA and protein expression than for the ABC transporters. The samples showed considerable interindividual variability, especially at the protein level. The apically located Pgp and MRP2 showed a similar expression pattern along the human intestine as for CYP3A4. The gene expression of MRP1 exhibited a more uniform distribution.
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| 2. |
- Bondi, J., et al.
(author)
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Randomized clinical trial comparing collagen plug and advancement flap for trans-sphincteric anal fistula
- 2017
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In: British Journal of Surgery. - : WILEY. - 0007-1323 .- 1365-2168. ; 104:9, s. 1160-1166
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Journal article (peer-reviewed)abstract
- Background: The role of a collagen plug for treating anal fistula is not well established. A randomized prospective multicentre non-inferiority study of surgical treatment of trans-sphincteric cryptogenic fistulas was undertaken, comparing the anal fistula plug with the mucosal advancement flap with regard to fistula recurrence rate and functional outcome.Methods: Patients with an anal fistula were evaluated for eligibility in three centres, and randomized to either mucosal advancement flap surgery or collagen plug, with clinical follow-up at 3 and 12 months. The primary outcome was the fistula recurrence rate. Anal pain (visual analogue scale), anal incontinence (St Mark's score) and quality of life (Short Form 36 questionnaire) were also reported.Results: Ninety-four patients were included; 48 were allocated to the plug procedure and 46 to advancement flap surgery. The median follow-up was 12 (range 9-24) months. The recurrence rate at 12 months was 66 per cent (27 of 41 patients) in the plug group and 38 per cent (15 of 40) in the flap group (P = 0.006). Anal pain was reduced after operation in both groups. Anal incontinence did not change in the follow-up period. Patients reported an increased quality of life after 3 months. There were no differences between the groups with regard to pain, incontinence or quality of life.Conclusion: There was a considerably higher recurrence rate after the anal fistula plug procedure than following advancement flap repair.
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| 3. |
- Cashin, Peter, et al.
(author)
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Acquired haemophilia A and Kaposi's sarcoma in an HIV-negative, HHV-8-positive patient : a discussion of mechanism and aetiology
- 2010
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In: Acta Haematologica. - : S. Karger AG. - 0001-5792 .- 1421-9662. ; 124:1, s. 40-43
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Journal article (peer-reviewed)abstract
- BACKGROUND: Acquired haemophilia A (AHA) is a rare bleeding disorder caused by an imbalance in the immune system leading to the production of factor VIII antibodies. In half of the cases, the underlying cause is not known. CLINICAL HISTORY: We report on a patient with AHA and Kaposi's sarcoma (KS), which is caused by the human herpes virus 8 (HHV-8). The patient presented with appendicitis and developed several severe post-operative haemorrhages. He spent 3 months in intensive care due to long and difficult infections. While recuperating on the ward, the patient developed KS in the lower extremities. He had a positive HHV-8 infection. DISCUSSION/CONCLUSION: Due to its latency and replication in the lymphoid system, HHV-8 is an ideal candidate for causing an imbalance in the immune system in susceptible patients. Our conclusion is that AHA was caused or prompted by the HHV-8 infection. Since HHV-8 viral infection is often subclinical, viral testing might be an important tool in acquired haemophilia diagnostics even when viral symptoms are absent.
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| 4. |
- Danielson, Johan, 1975-
(author)
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Anorectal Malformations : Long-term outcome and aspects of secondary treatment
- 2015
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Doctoral thesis (other academic/artistic)abstract
- Faecal incontinence (FI) is defined as the inability to control bowel movements. The causes of FI are many and diverse. One of the more uncommon reasons for FI is Anorectal Malformations (ARMs). An ARM is a congenital anomaly that affects somewhere between 1/2500 and 1/5000 live born babies. Many ARM patients have persistent FI. Several different procedures have been utilised to address this issue. This thesis aims to evaluate (1) the long-term outcome in adulthood of ARMs in relation to the modern Krickenbeck classification, and (2) scope for treating FI with transanal injection with dextranomer in non-animal stabilised hyaluronic acid (NASHA/Dx), in patients both with and without ARMs.All patients treated for ARMs in Uppsala up to 1993 were invited to participate in a questionnaire study of quality of life and function. The study included 136 patients and compared them with 136 age- and sex-matched controls. The Krickenbeck classification was found to predict functional outcome, and ARM patients had more problems with incontinence and obstipation, as well as inferior Quality of Life (QoL), compared with controls. Thirty-six patients with FI, owing to causes other than ARMs, were treated with transanal submucous injection of NASHA/Dx. The patients were monitored for two years after treatment. Significant reductions in both their incontinence score and the number of their incontinence episodes were achieved. A significant improvement in QoL was observed in patients who had at least a 75% reduction in incontinence episodes. No serious complications occurred.A prospective study of transanal injection of NASHA/Dx was conducted on seven patients with persistent FI after ARMs. After six months a significant reduction in the number of incontinence episodes was obtained. A significant improvement in QoL was also found. No serious complications occurred.In conclusion, adult patients with ARMs have inferior outcome of anorectal function and QoL compared with controls. NASHA/Dx is effective and appears to be safe in treating FI in general. This effect seems to be the same in selected patients with persistent FI after ARMs.
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| 5. |
- Danielson, Johan, 1975-, et al.
(author)
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Change in Deferring Time Correlate to Improved Female Sexual Function after Anal Sphincter Repair: A Prospective Study
- 2020
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In: Open Journal of Obstetrics and Gynecology. - : Scientific Research Publishing, Inc.. - 2160-8792 .- 2160-8806. ; 10:05, s. 729-737
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Journal article (peer-reviewed)abstract
- Background: Many women suffer from sexual problems after anal sphincter tears due to obstetric trauma. Aim: The study aimed to assess changes in sexual function after anal sphincter repair. Methods: The study was a non-randomized prospective observational cohort study. Inclusion of the study was done at the University Hospital, Uppsala, Sweden, between 2002 and 2007. Thirty-nine consecutive female patients admitted for anal sphincter repair were invited to the study. Twenty patients accepted and were included, four were lost to follow up and one was unevaluable (due to the formation of a stoma) leaving a study group of 15 patients. The patients were assessed with questionnaires before surgery and at three and 12 months after surgery. Outcomes: Change in reported sexual activity and dyspareunia. Results: Before surgery, 12/15 patients reported that their sexual life was impaired due to anal incontinence. The corresponding figure at 12 months was 9/15 (p = 0.43). Three patients remained sexually inactive throughout the study, five patients increased their sexual activity and one had decreased activity. Out of the 12 who were active, four stated dyspareunia at baseline, and only one reported dyspareunia at 12 months. The mean Miller incontinence scores at baseline and 12 months were 10.1 and 8.7, respectively. The change in incontinence score did not differ between those with decreased, stable or increased sexual activity. However, there was a definite correlation (r = 0.54 - 0.60, p < 0.05) between change in sexual function and deferring time for stool. Clinical Implications: Operative management of anal sphincter tears alone is not curative for sexual problems due to anal incontinence but can be a part of the treatment. Strengths and Limitations: The study is a prospective study of sexual function. The limitations are that the questionnaires were not validated due to lack of such questionnaires at the time of the study and that the study population is quite small. Conclusion: Patients with a sphincter injury and fecal incontinence often have an impaired sexual function. Increased deferring time for stools after surgery increases the likelihood of improved sexual function.
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| 6. |
- Danielson, Johan, 1975-, et al.
(author)
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Efficacy and quality of life 2 years after treatment for faecal incontinence with injectable bulking agents
- 2013
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In: Techniques in Coloproctology. - : Springer Science and Business Media LLC. - 1123-6337 .- 1128-045X. ; 17:4, s. 389-395
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Journal article (peer-reviewed)abstract
- BACKGROUND:Stabilized non-animal hyaluronic acid/dextranomer (NASHA® Dx) gel as injectable bulking therapy has been shown to decrease symptoms of faecal incontinence, but the durability of treatment and effects and influence on quality of life (QoL) is not known. The aim of this study was to assess the effects on continence and QoL and to evaluate the relationship between QoL and efficacy up to 2 years after treatment.METHODS:Thirty-four patients (5 males, mean age 61, range 34-80) were injected with 4 × 1 ml NASHA Dx in the submucosal layer. The patients were followed for 2 years with registration of incontinence episodes, bowel function and QoL questionnaires.RESULTS: Twenty-six patients reported sustained improvement after 24 months. The median number of incontinence episodes before treatment was 22 and decreased to 10 at 12 months (P = 0.0004) and to 7 at 24 months (P = 0.0026). The corresponding Miller incontinence scores were 14, 11 (P = 0.0078) and 10.5 (P = 0.0003), respectively. There was a clear correlation between the decrease in the number of leak episodes and the increase in the SF-36 Physical Function score but only patients with more than 75 % improvement in the number of incontinence episodes had a significant improvement in QoL at 24 months.CONCLUSIONS:Anorectal injection of NASHA Dx gel induces improvement of incontinence symptoms for at least 2 years. The treatment has a potential to improve QoL. A 75 % decrease in incontinence episodes may be a more accurate threshold to indicate a successful incontinence treatment than the more commonly used 50 %.
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| 7. |
- Danielson, Johan, 1975-, et al.
(author)
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Injectable bulking treatment of persistent faecal incontinence after anorectal malformations. A preliminary report.
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Other publication (other academic/artistic)abstract
- Background/PurposeDuring the last decades injectable bulking therapy has emerged as a promising treatment option for fecal incontinence (FI). Very little has been published on the use of injectable bulking therapy on patients with persistent FI after anorectal malformations (ARM). This study aimed to evaluate non-animal stabilized hyaluronic acid with dextranomer (NASHA/Dx) for the treatment of adult ARM patients with persistent FI.MethodsSeven adult patients with persistent FI after ARM were treated with perianal submucuos injection of NASHA/Dx. They were evaluated preoperatively and at three and six months after treatment with a validated bowel function questionnaire and a two-week bowel diary as well as FIQL and SF-36 quality of life questionnaires.ResultsBefore treatment mean Miller incontinence score was 13,7 and the mean number of incontinence episodes over two weeks was 20,7. At 6 months after treatment the corresponding figures were 10,7 (P=0,1088) and 5,3 (P=0,0180) respectively. No significant changes could be found in either FIQL or SF-36 scores. No serious adverse events occurred during the study.ConclusionsNASHA/Dx is a promising treatment option for selected adult patients with persistent FI after ARM. Long-term follow up of larger patient series as well as studies on patients in adolescence are needed.
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| 8. |
- Danielson, Johan, 1975-, et al.
(author)
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Injectable bulking treatment of persistent fecal incontinence in adult patients after anorectal malformations
- 2020
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In: Journal of Pediatric Surgery. - : W B SAUNDERS CO-ELSEVIER INC. - 0022-3468 .- 1531-5037. ; 55:3, s. 397-402
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Journal article (peer-reviewed)abstract
- Background/Purpose: Injectable bulking therapy has emerged as a treatment for fecal incontinence (IT, however there are no studies including adult patients with anorectal malformations (ARM). This study aimed to evaluate non-animal stabilized hyaluronic add with dextranomer (NASHA/Dx) for the treatment of adult ARM patients with persistent FI.Methods: Seven adults with ARM and incontinence to loose stool at least once weekly and without rectal or mucosal prolapse were treated with anal NASHA/Dx injection. They were evaluated preoperatively, at 6 and 18 months with a bowel function questionnaire and a 2-week bowel diary as well as FTQL and SF-36 quality of life questionnaires.Results: Before treatment, the mean number of incontinence episodes over 2 weeks was 20.7 (median 16, range 8-52). At 6 months, the corresponding figures were 53 (median 4, range 0-19, p = 0.018), and at 18 months the figures were 4.3 (median 2, range 1-20,p = 0.018). An improved physical function in SF-36 from 74.3 at baseline to 86.4 at 6 months was noted (p = 0.04). No serious adverse events occurred.Conclusions: NASHA/Dx is a promising treatment option for selected adult patients with persistent Ft after ARM. Longer follow up of larger patient series and studies on patients in adolescence is needed.
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| 9. |
- Danielson, Johan, 1975-, et al.
(author)
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Long-Term Outcome after Dynamic Graciloplasty for Treatment of Persistent Fecal Incontinence in Patients with Anorectal Malformations
- 2019
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In: European journal of pediatric surgery. - : GEORG THIEME VERLAG KG. - 0939-7248 .- 1439-359X. ; 29:3, s. 276-281
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Journal article (peer-reviewed)abstract
- Purpose Dynamic graciloplasty (DGP) has been used to treat severe fecal incontinence since the 1980s. Previous studies have shown an inferior outcome in patients with anorectal malformations (ARMs). Our experience has been that DGP has been appreciated by ARM -patients. The objective of the study was to evaluate the long-term outcome of DGP in our patients with ARM compared with patients with other underlying conditions. Materials and Methods Twenty-three patients operated with DGP at our institution from 1996 to 2010 were sent validated bowel function and quality of life questionnaires. Eighteen of 23 responded. Seven had ARM and 11 had other etiologies of fecal incontinence. The mean follow-up time was 11.6 years (range, 5-17). Results Four of 7 of the patients with ARM and 8 of 11 of patients with other etiologies used their implants at follow-up. The Miller incontinence score was slightly higher for patients with ARMs, but they had less constipation and higher Fecal Incontinence Quality of Life (FIQL)- and 36-Item Short Form Health Survey (SF-36) scores. None of the differences were statistically significant. Conclusion This study cannot confirm earlier reports in which DGP has an inferior outcome in patients with ARM. We therefore believe that the procedure should remain a treatment option for selected patients.
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| 10. |
- Danielson, Johan, et al.
(author)
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Long-term outcome after free autogenous muscle transplantation for anal incontinence in children with anorectal malformations
- 2010
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In: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 45:10, s. 2036-2040
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Journal article (peer-reviewed)abstract
- PURPOSE: Patients with high anorectal anomalies are often incontinent after reconstruction, particularly with the older forms of surgical treatment, that is, anorectal pull-through or Stephen's operations. In 1974, a new treatment for anal incontinence in children was introduced at the Akademiska Hospital: free autogenous muscle transplantation (FAMT) to the perirectal area. All the patients receiving FAMT were totally incontinent before the procedure and had no rectal sensitivity. The aim of this study was to evaluate the long-term functional outcome of this procedure. METHODS: Twenty-two patients (17 males) operated on with FAMT below the age of 15 years were identified through records. One of the patients had died, and 2 were not available for follow-up. The remaining 19 were sent a validated bowel function questionnaire, and 15 (78.9%) of 19 patients responded (12 males). These 15 patients were compared with 15 patients with the same sex, age, and a similar malformation from our patient database. RESULTS: At follow-up, after an average of 30 years postoperatively, 2 of 15 patients with FAMT had a stoma compared with 3 of 15 in the control group. The Miller incontinence score had a mean of 6.2 (median, 6; range, 0-15) in the FAMT group and 3.7 (median, 4; range, 0-12) in the control group. All patients in both groups could sense stool, and 11 of 13 patients in the FAMT group could distinguish between feces and flatus. CONCLUSIONS: The patients with FAMT had a slightly inferior anorectal function compared with the controls. Considering they were all totally incontinent before FAMT, we conclude that FAMT has an acceptable effect 30 years postoperatively. Therefore, we find that FAMT could be an alternative for anorectal malformation patients who are totally incontinent.
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