| 1. |
|
|
| 2. |
- Jansson, Markus, 1982-, et al.
(författare)
-
Fecal incontinence and associated pelvic floor dysfunction during and one year after the first pregnancy
- 2023
-
Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 102:8, s. 1034-1044
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Obstetric anal sphincter injury is an important risk factor for postpartum fecal incontinence but few studies have reported fecal incontinence occurring, even during pregnancy. The first objective of this study was to examine the prevalence of fecal incontinence, obstructed defecation and vaginal bulging early and late in pregnancy and postpartum. The second objective was to assess the association between symptoms in pregnancy, delivery characteristics, and bowel and vaginal bulging symptoms at 1 year postpartum.MATERIAL AND METHODS: This prospective cohort study was conducted between October 2014 and October 2017, including 898 nulliparous women enrolled with the maternity healthcare service in Örebro County, Sweden. The women responded to questionnaires regarding pelvic floor dysfunction in early and late pregnancy and at 8 weeks and 1 year postpartum. The data were analyzed using random effect logistic models estimating odds ratios (ORs) and generalized linear models estimating relative risks, with 95% confidence intervals (CIs).RESULTS: At 1 year postpartum, the prevalence of fecal incontinence, obstructed defecation and vaginal bulging was 6% (40/694), 28% (197/699) and 8% (56/695), respectively. Among women with vaginal delivery, the risk of fecal incontinence and vaginal bulging increased significantly both in late pregnancy, with ORs of 3.4 (95% CI 1.5-7.7) and 3.6 (95% CI 1.6-8.1), respectively, and at 1 year postpartum, with ORs of 5.0 (95% CI 2.1-11.5) and 8.3 (95% CI 3.8-18.1), respectively, compared with early pregnancy. Among all women, factors associated with increased prevalence of fecal incontinence 1 year postpartum were fecal incontinence during pregnancy (adjusted relative risk [aRR] 7.4; 95% CI 4.1-13.3), obstructed defecation during pregnancy (aRR 2.0; 95% CI 1.1-3.9) and concurrent obstructed defecation (aRR 2.4; 95% CI 1.3-4.5).CONCLUSIONS: This prospective study shows an increased risk of fecal incontinence by late pregnancy, suggesting that the pregnancy itself may be involved in the development of postpartum fecal incontinence. Obstructed defecation during pregnancy and postpartum was found to be associated with increased risk of fecal incontinence postpartum, indicating that postpartum fecal incontinence may be a result of incomplete bowel emptying.
|
|
| 3. |
|
|
| 4. |
- Jansson, Markus, 1982-
(författare)
-
Pelvic Floor Dysfunction and Perineal and Vaginal Tears in Primiparous Women
- 2022
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pelvic floor dysfunction (PFD), including urinary incontinence, faecal incontinence (FI), and pelvic organ prolapse, is highly prevalent among parous women. There is evidence that pregnancy, vaginal delivery, and obstetric perineal tears increase the risk of pelvic floor dysfunction, but many of the studies in this field are retrospective. The overall aim of this thesis was to prospectively examine risk factors for perineal and vaginal tears and postpartum PFD in primiparous women.Study I was a validation study of a protocol for documentation of perineal tears, including 187 primiparous women in 2015–2016. The coverage of documentation was higher in the protocol compared to the obstetric record system (ObstetriX). Incidence of second degree perineal tears was 26% according to the protocol and 11% according to ObstetriX.Studies II–IV utilized a cohort of initially nulliparous women (n=1049) prospectively included in early pregnancy in 2014–2017. Women completed questionnaires on PFD in early and late pregnancy and at 8 weeks and 1 year postpartum.Study II (n=644) showed that high foetal weight and vacuum extraction were risk factors for both second degree tears and OASI, suggesting that these tears should be viewed as a continuum rather than different entities. Risk factors for high vaginal tears were large foetal head circumference, vacuum extraction, and heredity of PFD/connective tissue deficiency. Study III (n=670) found that vaginal delivery increased the risk of stress urinary incontinence (SUI) but not urgency urinary incontinence (UUI) 1 year postpartum. No single characteristic of the vaginal delivery was associated with SUI. SUI during pregnancy increased the risk of SUI postpartum, and UUI during pregnancy increased the risk of UUI postpartum.Study IV (n=898) showed that FI increased by late pregnancy, and that this increase persisted 1 year postpartum. Obstructed defecation was associated with increased FI postpartum, suggesting that post-defecatory faecal loss may be an underlying mechanism of FI. Overall conclusion: The extent to which pregnancy, vaginal delivery, and their respective characteristics contributed to the development of PFD differed between the pelvic floor disorders studied. For SUI, both the pregnancy and the vaginal delivery increased the risk, whereas for FI it was the pregnancy itself rather than the vaginal delivery that was demonstrated to increase the risk.
|
|
| 5. |
- Jansson, Markus, 1982-, et al.
(författare)
-
Risk factors for perineal and vaginal tears in primiparous women : the prospective POPRACT-cohort study
- 2020
-
Ingår i: BMC Pregnancy and Childbirth. - : BioMed Central. - 1471-2393 .- 1471-2393. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to estimate the incidence of second-degree perineal tears, obstetric anal sphincter injuries (OASI), and high vaginal tears in primiparous women, and to examine how sociodemographic and pregnancy characteristics, hereditary factors, obstetric management and the delivery process are associated with the incidence of these tears.Methods: All nulliparous women registering at the maternity health care in Region Örebro County, Sweden, in early pregnancy between 1 October 2014 and 1 October 2017 were invited to participate in a prospective cohort study. Data on maternal and obstetric characteristics were extracted from questionnaires completed in early and late pregnancy, from a study-specific delivery protocol, and from the obstetric record system. These data were analyzed using unadjusted and adjusted multinomial and logistic regression models.Results: A total of 644 women were included in the study sample. Fetal weight exceeding 4000 g and vacuum extraction were found to be independent risk factors for both second-degree perineal tears (aOR 2.22 (95% CI: 1.17, 4.22) and 2.41 (95% CI: 1.24, 4.68) respectively) and OASI (aOR 6.02 (95% CI: 2.32, 15.6) and 3.91 (95% CI: 1.32, 11.6) respectively). Post-term delivery significantly increased the risk for second-degree perineal tear (aOR 2.44 (95% CI: 1.03, 5.77), whereas, maternal birth positions with reduced sacrum flexibility significantly decreased the risk of second-degree perineal tear (aOR 0.53 (95% CI 0.32, 0.90)). Heredity of pelvic floor dysfunction and/or connective tissue deficiency, induced labor, vacuum extraction and fetal head circumference exceeding 35 cm were independent risk factors for high vaginal tears (aOR 2.32 (95% CI 1.09, 4.97), 3.16 (95% CI 1.31, 7.62), 2.53 (95% CI: 1.07, 5.98) and 3.07 (95% CI 1.5, 6.3) respectively).Conclusion: The present study corroborates previous findings of vacuum extraction and fetal weight exceeding 4000 g as risk factors of OASI. We found that vacuum extraction is a risk factor for second-degree tear, and vacuum extraction, fetal head circumference exceeding 35 cm and heredity of pelvic floor dysfunction and/or connective tissue deficiency were associated with increased risk of high vaginal tears. These findings have not been documented previously and should be confirmed by additional studies.
|
|
| 6. |
- Jansson, Markus, 1982-, et al.
(författare)
-
Stress and urgency urinary incontinence one year after a first birth-prevalence and risk factors : A prospective cohort study
- 2021
-
Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 100:12, s. 2193-2201
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Few prospective studies have examined the effect of pregnancy and childbirth on stress and urgency urinary incontinence separately. The aim of the present study was to assess the extent to which pregnancy, vaginal delivery, and vaginal delivery characteristics affect the risk of significant stress and urgency incontinence 1 year after delivery.MATERIAL AND METHODS: We conducted a prospective cohort study of 670 nulliparous women from early pregnancy to 1 year partum. The women were recruited at maternity health care service in Region Örebro County, Sweden, between October 1, 2014 and October 1, 2017 and completed questionnaires in early and late pregnancy and at 8 weeks and 1 year postpartum. Primary outcome measures were significant stress and urgency incontinence at 1 year postpartum in women who reported being continent before pregnancy. Generalized linear models were used.RESULTS: Stress and urgency incontinence commencing before pregnancy were reported by 4% and 3% of women, respectively, in the first questionnaire in early pregnancy, and these women were excluded from subsequent analysis. Stress and urgency incontinence were reported by 21% and 8%, respectively, at 1 year postpartum, in women not reporting incontinence before pregnancy. Stress incontinence during pregnancy increased the risk of stress incontinence postpartum (risk ratio [RR] 2.48, 95% CI 1.86-3.3). Urgency incontinence during pregnancy increased the risk of urgency incontinence postpartum (RR 4.07, 95% CI 2.1-7.89). Vaginal delivery increased the risk of stress incontinence postpartum (adjusted RR 2.63, 95% CI 1.39-5.01) but not of urgency incontinence. This effect of vaginal delivery on stress incontinence was similar irrespective of incontinence status during pregnancy. The population-attributable fraction of stress incontinence associated with vaginal delivery was 0.58 (95% CI 0.23-0.77).CONCLUSIONS: This study shows essentially different risk factors for stress and urgency incontinence, supporting stress incontinence as being the subtype mostly associated with pregnancy and childbirth, and urgency incontinence as being more stable over time. At a population level, vaginal delivery was the major risk factor for stress incontinence, followed by reporting stress incontinence during pregnancy.
|
|
| 7. |
- Magnusson, Kristina, et al.
(författare)
-
Specific Uptake of an Amyloid-beta Protofibril-Binding Antibody-Tracer in A beta PP Transgenic Mouse Brain
- 2013
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 37:1, s. 29-40
-
Tidskriftsartikel (refereegranskat)abstract
- Evidence suggests that amyloid-beta (A beta) protofibrils/oligomers are pathogenic agents in Alzheimer's disease (AD). Unfortunately, techniques enabling quantitative estimates of these species in patients or patient samples are still rather limited. Here we describe the in vitro and ex vivo characteristics of a new antibody-based radioactive ligand, [I-125]mAb158, which binds to A beta protofibrils with high affinity. [I-125]mAb158 was specifically taken up in brain of transgenic mice expressing amyloid-beta protein precursor (A beta PP) as shown ex vivo. This was in contrast to [I-125]mAb-Ly128 which does not bind to A beta. The uptake of intraperitoneally-administered [I-125]mAb158 into the brain was age- and time-dependent, and saturable in A beta PP transgenic mice with modest A beta deposition. Brain uptake was also found in young A beta PP transgenic mice that were devoid of A beta deposits, suggesting that [I-125]mAb158 targets soluble A beta protofibrils. The radioligand was diffusely located in the parenchyma, sometimes around senile plaques and only occasionally colocalized with cerebral amyloid angiopathy. A refined iodine-124-labeled version of mAb158 with much improved blood-brain barrier passage and a shorter plasma half-life might be useful for PET imaging of A beta protofibrils.
|
|
| 8. |
- Tegerstedt, Karin
(författare)
-
Studies on polyomavirus virus-like particles : as vaccines and vectors for immune and gene therapy
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Virus-like particles (VLPs) are similar to natural virus particles except that they lack viral genes. They have a similar cellular uptake to the natural virus from which they are derived but are non-infectious and can therefore not reproduce themselves. VLPs have been used as a model to understand viral entry, infection and cell tropism, but have also been shown to be useful in other areas e.g. as vaccines against viral infection, as well as carriers for molecules in immune and gene therapy. This thesis is based on VLPs from two related viruses, murine polyomavirus (MPyV) and murine pneumotropic virus (MPtV) and the aim has been to investigate their possible use as viral vaccines and as vectors in gene and immune therapy. Both viruses consist of only a few genes and a protein capsid surrounding them. MPyV was discovered when it was shown to induce tumors in mice, thereof the name, “polyoma”, Greek for many tumors. It is easy to grow in cell culture, and because of its oncogenic potential and its small size it has been an important research tool in molecular biology. Studies on MPyV have led to many discoveries in understanding cellular events like DNA replication, cell growth regulation, and genes involved in tumor development. The MPtV on the other hand, is non-oncogenic, is difficult to grow and has not been well studied. We have been successful in producing VLPs from both these viruses, and used them as immunogens and as carriers for tumor antigens. They should both be suitable for therapeutic use in humans, since they are of non-human origin, and humans have no pre-existing immunity against them. In the first paper, the aim was to optimize MPyV-vaccination by examining the importance of the route of administration and the VLP structure. All, even immune deficient, mice were protected against subsequent MPyV infection by changing from intraperitoneal to subcutaneous VLP vaccination. Furthermore, VLPs were more efficient, than the more linear GST-VP1 in viral protection and in the induction of an antibody response. The conclusion from this study was that, the route of administration, and the antigenic structure are important. This antibody response is of value for MPyV vaccination, but more of an obstacle when using MPyV-VLPs as antigen carriers, where the antibodies may abolish the effect of a similar second treatment. Therefore the aim of the second study was to study VLPs from MPtV, as a possible complement to e.g. MPyV-VLPs. MPtV-VLPs were successfully produced; they entered all cell types tested and did not cross-react with MPyV-VLPs, which make them suitable as complement to MPyV-VLPs in prime-boost therapy. In the third paper MPyV-VLPs carrying the oncoprotein Her2, Her21-683PyVLPs, were successfully produced and were used to vaccinate against Her2-expressing tumors. Vaccination with Her21-683PyVLPs efficiently protected mice from tumor outgrowth of the transplantable Her2 positive tumor D2F2/E2, as well as against spontaneous mammary carcinoma outgrowth in BALBneuT mice, transgenic for rat Her2. In the fourth study, Her21-683PyVLP vaccination was compared to vaccination with Her21-683PyVLPs loaded on dendritic cells (DCs), with regard to efficiency and to anti-VLP response. Vaccination with Her21-683PyVLP loaded DCs was more efficient in protecting mice against outgrowth of D2F2/E2 tumor where a lower Her21-683PyVLP dose was sufficient for full protection, compared to vaccination with Her21-683PyVLPs alone. Furthermore; vaccination with Her21-683PyVLP loaded DCs resulted in lower anti-VLP titers. In conclusion, VLPs derived from mouse polyomaviruses can be used to vaccinate against a subsequent polyoma infection. Moreover, they can be used as carriers for molecules in immune and gene therapy. We show that VLPs have substantial potential for use in cancer immune therapy, and that MPyV-VLPs and MPtV-VLPs, due to lack of cross-reactivity, should be complementary and suitable for prime-boost therapy.
|
|
| 9. |
- Tucker, Stina, et al.
(författare)
-
The Murine Version of BAN2401 (mAb158) Selectively Reduces Amyloid-beta Protofibrils in Brain and Cerebrospinal Fluid of tg-ArcSwe Mice
- 2015
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 43:2, s. 575-588
-
Tidskriftsartikel (refereegranskat)abstract
- Amyloid-beta (A beta) immunotherapy for Alzheimer's disease (AD) has good preclinical support from transgenic mouse models and clinical data suggesting that a long-term treatment effect is possible. Soluble A beta protofibrils have been shown to exhibit neurotoxicity in vitro and in vivo, and constitute an attractive target for immunotherapy. Here, we demonstrate that the humanized antibody BAN2401 and its murine version mAb158 exhibit a strong binding preference for A beta protofibrils over A beta monomers. Further, we confirm the presence of the target by showing that both antibodies efficiently immunoprecipitate soluble A beta aggregates in human AD brain extracts. mAb158 reached the brain and reduced the brain protofibril levels by 42% in an exposure-dependent manner both after long-term and short-term treatment in tg-ArcSwe mice. Notably, a 53% reduction of protofibrils/oligomers in cerebrospinal fluid (CSF) that correlated with reduced brain protofibril levels was observed after long-term treatment, suggesting that CSF protofibrils/oligomers could be used as a potential biomarker. No change in native monomeric A beta(42) could be observed in brain TBS extracts after mAb158-treatment in tg-ArcSwe mice. By confirming the specific ability of mAb158 to selectively bind and reduce soluble A beta protofibrils, with minimal binding to A beta monomers, we provide further support in favor of its position as an attractive new candidate for AD immunotherapy. BAN2401 has undergone full phase 1 development, and available data indicate a favorable safety profile in AD patients.
|
|
