A Bergqvist

Karolinska Institutet, Сольна, Stockholm, Sweden

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Publications (84)242.09 Total impact

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    ABSTRACT: To estimate the relative contribution of genetic influences and prevalence on endometriosis. Analysis of self-reported data from a nationwide population-based twin registry. Not applicable. In total 28,370 women, female monozygotic (MZ) or dizygotic (DZ) twins, who participated in either of two surveys (1998-2002 or 2005-2006). None. Self-reported endometriosis, validated by medical records. A history of endometriosis was reported by 1,228 female twins. The probandwise concordance was 0.21 for MZ and 0.10 for DZ twins. Higher within-pair (tetrachoric) correlation was observed among MZ (0.47) compared with DZ (0.20) twins. The best-fitting model revealed a contribution of 47% by additive genetic factors and the remaining 53% attributed to unique environmental effects. Our findings suggest both genetic and unique (nonshared) environmental influences on the complex etiology of endometriosis and support the hypothesis that genes have a strong influence on phenotypic manifestations of endometriosis. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Jul 2015 · Fertility and sterility
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    ABSTRACT: OBJECTIVE: Whether hormonal or surgical treatment of endometriosis is associated with risk of epithelial ovarian cancer. DESIGN: Nested case-control study. SETTING: Sweden. POPULATION: All women with a first-time discharge diagnosis of endometriosis in 1969-2007 were identified using the National Swedish Patient Register and constituted our study base. METHODS: By linkage to the National Swedish Cancer Register we identified all women diagnosed with epithelial ovarian cancer at least one year after the endometriosis diagnosis (cases). Two controls per case with no ovarian cancer before the date of cancer diagnosis of the case were randomly selected from the study base and matched for year of birth. Two-hundred-and-twenty cases and 416 controls entered the study. Information on hormonal and surgical treatments and other reproductive factors was extracted from medical records according to pre-specified protocols. Conditional logistic regression was used for all calculations. MAIN OUTCOME MEASURES: Crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) for all hormonal as well as surgical treatments. RESULTS: There was a significant association between one-sided oophorectomy, as well as for radical extirpation of all visible endometriosis, and ovarian cancer risk in both univariate analyses (crude OR 0.42, 95% CI 0.28-0.62 and OR 0.37, 95% CI 0.25-0.55, respectively) and multivariate analyses (adjusted OR 0.19, 95% CI 0.08-0.46 and OR 0.30, 95% CI 0.12-0.74, respectively). CONCLUSIONS: One-sided oophorectomy as well as radical extirpation of all visible endometriosis is protective against later development of ovarian cancer.
    No preview · Article · Apr 2013 · Acta Obstetricia Et Gynecologica Scandinavica
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    A Melin · C Lundholm · N Malki · M-L Swahn · P Sparen · A Bergqvist
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    ABSTRACT: Studies have shown an increased risk of malignancies in women with endometriosis. Little is known about the impact of endometriosis on cancer survival. We investigated whether the survival after a diagnosis of a malignancy differs in women with a previously diagnosed endometriosis compared to other women. Women with a first time diagnosis of a malignancy in 1969-2005, were identified using the National Swedish Cancer Register (NSCR). By use of the National Swedish Patient Register (NSPR) we identified all women with a diagnosis of endometriosis during the same period and linked these patients with the data from the NSCR. The cohort comprised 4,278 women with endometriosis and a malignancy, and 41,831 randomly selected matched women without endometriosis. Cox regression was used for all calculations to obtain crude and adjusted cause specific mortality rates, measured as hazard ratios (HR) with 95% confidence intervals (CI). A total of 46,109 women entered the study. There was a statistically significant better survival for women with endometriosis for all malignancies combined (HR=0.92) and for breast cancer (HR=0.86) and ovarian cancer (HR=0.81) specifically. For breast cancer the survival enhancing effect in women with endometriosis decreased with increasing parity. There was poorer survival in malignant melanoma for women with endometriosis (HR=1.52). The survival in a malignancy is better in women with a previously diagnosed endometriosis compared to women without endometriosis especially for breast and ovarian cancers. The prognosis of malignant melanoma is poorer in women with endometriosis.
    Full-text · Article · Aug 2011 · International Journal of Cancer
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    ABSTRACT: Introduction The prevalence of endometriosis is difficult to estimate as the diagnosis requires surgery. In several cohort studies it has been estimated to affect 5-10 % of women in reproductive age. The pathogenesis is probably multifactorial, but heredity is one important factor and it is hypothesized that endometriosis has a genetic basis. One standard approach to determine whether or not a disease has a genetic basis is to calculate the concordance rates in large twin populations. Material and Methods The Swedish Twin Registry (STR) is the largest twin registry in the world and includes all twins born in Sweden since 1886. Two cross-sectional data bases are available: SALT (Screening across the life-span twin study) data collected 1998-2002, includes twins born 1886-1958. STAGE (Swedish twin study of adult's genes and environments) data collected 2005-2006, includes twins born 1959-1985. At data collection specific questions related to women's health and partly specific for endometriosis were included. The data from all female twin pairs who answered the questions about endometriosis constitute the study base. Both sets of data (SALT and STAGE) were analyzed for prevalence and concordance of endometriosis. All female twins who answered the questionnaire but who did not respond to the particular questions about endometriosis were also identified. All female twins with a discharge diagnosis of endometriosis were identified by linking the National Swedish Patient registry (NSPR) to the SALT and the STAGE data bases and the diagnosis of twins who had answered yes to the question if they had endometriosis could be confirmed. Some additional twins were identified with the diagnosis endometriosis through NSPR although they were non responders to the questionnaire or answered that they did not have endometriosis. Results In the SALT database in total 5 953 (11 906 individuals) complete female twin pairs (monozygotic, MZ and dizygotic, DZ) were identified. The prevalence of endometriosis was 5.3 % (635/11906). The pair wise concordance rate was 19.9 % and the proband wise concordance rate was 33.2 % in MZ twin pairs. The pair wise concordance rate was 14.4 % and the proband wise concordance rate was 25.1 % in DZ twin pairs. In the STAGE database in total 3790 (7580 individuals) complete female twin pairs (MZ and DZ) were identified. The prevalence of endometriosis was 4 % (301/7580). The pair wise concordance rate was 12.8 % and the proband wise concordance rate was 22.7 % in MZ twin pairs. The pair wise concordance rate was 4.3 % and the proband wise concordance rate was 8.3 % in DZ twin pairs. The distribution in age cohort of 5 years intervals of birth year of the 936 women who had endometriosis was highest, 17.5 %, in those born 1943-47 and lowest, 2.7 %, in those born 1978-1982. Conclusion The prevalence of endometriosis was 5 % in female twins aged ≥40 years and 4% in female twins between the ages 20-40 years, hence, somewhat lower than in some previous reports. Higher concordance rates among MZ than DZ twin pairs indicate that endometriosis has a genetic basis.
    No preview · Article · Jun 2010 · Human Reproduction
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    ABSTRACT: Hormonal suppressive therapy is not effective for endometriosis-associated subfertility and can even prevent conception. Medical inhibition of TNFalpha, which has been shown to improve conception, is effective in the prevention and treatment of endometriosis in baboons. Prospective, placebo-controlled fertility trial. Animal research and laboratory facility. Sixteen adult female baboons with induced endometriosis. All animals received a single IV dose of the anti-TNFalpha monoclonal antibody c5N (n = 9) or placebo (n = 7) at four different time points. The animals were then exposed to timed mating up to nine completed cycles or until pregnancy was achieved. Pregnancy rate (PR), cycle fecundity rate (CFR), time to pregnancy (TTP), and cumulative pregnancy rate (CPR). Inhibition of TNFalpha did not result in a significant improvement in PR (100% c5N vs. 86% placebo), CFR (18% c5N vs. 30% placebo), median TTP (5 cycles c5N vs. 2 cycles placebo), or CPR (100% c5N vs. 80% placebo). The duration of the menstrual cycle was unchanged in both groups before and after the study. Two nonpregnant baboons in the c5N-group died during the study. Medical inhibition of TNFalpha allowed for normal conception but did not improve fecundity in baboons with induced endometriosis when compared with placebo. Larger studies with clinically available TNFalpha blockers in baboons with moderate to severe endometriosis are needed to further test the potential of these agents in the prevention or treatment of endometriosis-associated subfertility.
    Full-text · Article · Jun 2008 · Fertility and sterility
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    A Melin · P Sparén · A Bergqvist
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    ABSTRACT: Several epidemiological studies have shown an increased cancer risk among women with endometriosis, especially ovarian cancer. Infertility and nulliparity are also known risk factors for different types of cancer. The aim of this study is to investigate cancer risk among women with endometriosis, stratifying for parity. Women discharged from a hospital, with the diagnosis of endometriosis from 1969 to 2002, were identified using the National Swedish Inpatient Register. Data were linked to the National Swedish Cancer Register to identify cases of cancer and to the Swedish Multi-Generation Register to calculate parity and age at first birth. Standardized incidence ratios (SIR) were calculated. A total of 63,630 women entered the study. To exclude cancers already present at the time of endometriosis diagnosis, the first year of follow-up was excluded, leaving a number of 3,822 cases of cancer. There was no increased overall risk of cancer (SIR 1.01) among women with endometriosis. Endometriosis was associated with elevated risks for endocrine tumours (SIR 1.38), ovarian cancer (SIR 1.37), renal cancer (SIR 1.36), thyroid cancer (SIR 1.33), brain tumours (SIR 1.27), malignant melanoma (SIR 1.23) and breast cancer (SIR 1.08), as well as a reduced risk for cervical cancer (SIR 0.71). There were no significant differences between nulliparous and parous women with endometriosis regarding cancer risk for any of the cancer types. There was a non-significant decrease in risk of ovarian cancer with increasing parity for women with endometriosis. Women with endometriosis have an increased risk for several malignancies. The increased risks do not seem to be related to parity.
    Preview · Article · Dec 2007 · Human Reproduction
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    ABSTRACT: Inflammatory cytokines, including interleukin (IL)-1, IL-6, IL-8 and tumour necrosis factor-alpha (TNF-alpha), are important in the pathogenesis of endometriosis. We assessed the efficacy of anti-TNF monoclonal antibody (mAb, c5N), known to prevent induced endometriosis in baboons, in reducing established endometriosis in baboons. This prospective, randomized, blinded, controlled study was conducted in baboons at the Institute of Primate Research (IPR), Nairobi, Kenya. Endometriosis was induced in 18 adult female baboons (Papio anubis) with regular menstrual cycles and a normal pelvis; the extent of endometriosis was documented by videolaparoscopy 25 days later. The baboons were then randomly assigned to receive a single infusion of either placebo (n=7, 5 ml/kg) or c5N (n=11, 5 mg/kg). Follow-up laparoscopy was performed 25 days later to document any differences in the number, surface area and estimated volume of lesions between the two groups and between the first and the second laparoscopies in each group. Representative biopsies of at least one endometriotic lesion per baboon were obtained at the final laparoscopy. Significant reductions in total surface area, estimated total volume of endometriotic lesions and both number and surface area of red lesions were observed after treatment with c5N, but not after placebo treatment, when compared to the initial laparoscopy. Conversely, a significant increase in the number of typical and red lesions was observed after placebo treatment when compared to the initial laparoscopy. Neither c5N nor placebo treatment affected the menstrual cycle. In baboons with induced endometriosis, anti-TNF-mAb (c5N) treatment significantly reduced the extent of endometriosis, mainly due to reducing both the number and surface area of red lesions. These findings suggest that anti-TNF-mAb therapy may have therapeutic potential for active peritoneal endometriosis.
    Full-text · Article · Aug 2006 · Human Reproduction
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    ABSTRACT: Endogenous retroviruses (ERVs) probably originate from ancient germ cell infections by exogenous retroviruses. A high expression of retroviruses in reproductive tissue increases the risk of viral transmission to germ line cells. We therefore investigated the expression of human ERVs (HERVs) in normal endometrium, endometriosis, normal ovaries, and ovarian cancer. Four real-time PCRs (QPCRs) for HERV-E, HERV-I/T, HERV-H, and HERV-W, respectively, and an expression control gene were used. HERV-E RNA expression was significantly higher in endometriotic tissue (average, SD) than in normal endometrium (average, SD), both measured as ratios versus control gene expression and as. HERV-E and HERV-W RNA were higher in normal ovarian tissue than in ovarian cancer. This illustrates that HERV expression is not automatically higher in malignant tissues. The other HERV PCRs did not show expression patterns as distinctive as HERVE and HERV-W in the two kinds of reproductive tissue. A small number of candidate HERV-E loci from which the transcription took place were identified by sequencing of amplimers. The role of HERV-E and HERV-W in endometriosis merits further investigation.
    No preview · Article · Jul 2006 · AIDS Research and Human Retroviruses
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    A Melin · P Sparén · I Persson · A Bergqvist
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    ABSTRACT: Several observations of the coexistence of endometriosis and cancer have been published. One study concerning endometriosis patients from 1969 to 1986 showed an overall relative cancer risk of 1.2 and relative risks for breast cancer, ovarian cancer and non-Hodgkin's lymphoma to be 1.3, 1.9 and 1.8, respectively. The aim of this study was to see whether these risk ratios stand in an extended study with longer follow-up. Women discharged from a hospital, with a diagnosis of endometriosis from 1969 to 2000, were identified using the National Swedish Inpatient Register. Data were linked to the National Swedish Cancer Register to identify cases of cancer. Data on hysterectomies and oophorectomies were available. Standardized incidence ratios (SIR) were calculated. 64 492 women entered the study. First year of follow-up was excluded, leaving 3349 cases of cancer. There was no increased overall risk of cancer [SIR 1.04, 95% CI 1.00-1.07]. Elevated risks were found for ovarian cancer (SIR 1.43, 95% CI 1.19-1.71), endocrine tumours (SIR 1.36, 95% CI 1.15-1.61), non-Hodgkin's lymphoma (SIR 1.24, 95% CI 1.02-1.49) and brain tumours (SIR 1.22, 95% CI 1.04-1.41). Women with early diagnosed and long-standing endometriosis had a higher risk of ovarian cancer, with SIR of 2.01 and 2.23, respectively. The average age at endometriosis diagnosis was 39.4, indicating that there are the moderate/severe cases that are included in this study. Women who had a hysterectomy before or at the time of the endometriosis diagnosis did not show an increased risk of ovarian cancer. Women with endometriosis have an increased risk of some malignancies, particularly ovarian cancer, and the risk increases with early diagnosed or long-standing disease. Hysterectomy may have a preventive effect against ovarian cancer.
    Full-text · Article · Jun 2006 · Human Reproduction
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    P.G. Crosignani · A Luciano · A Ray · A Bergqvist
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    ABSTRACT: A clinical study compared efficacy and safety of depot medroxyprogesterone acetate (DMPA) with leuprolide for endometriosis-associated pain. This multicentre, 18 month, evaluator-blinded, comparator-controlled trial randomized 300 women with laparoscopically diagnosed endometriosis to 6 month treatment with subcutaneous injection of 104 mg/0.65 ml DMPA (DMPA-SC 104) every 3 months or leuprolide (3.75 mg monthly or 11.25 mg every 3 months), with 12 months post-treatment follow-up. Endpoints included patient response to treatment in five signs/symptoms (dysmenorrhoea, dyspareunia, pelvic pain, pelvic tenderness, induration) and changes in bone mineral density (BMD) and productivity at 6 and 18 months. DMPA-SC 104 and leuprolide produced equivalent (P < 0.02) reductions in at least four pain categories and significant (P < 0.001) improvements in composite score at months 6 and 18. At month 6, reductions in total hip and lumbar spine BMD were significantly less (P < 0.001) with DMPA-SC 104 versus leuprolide. BMD returned to pre-treatment levels 12 months post-treatment in the DMPA-SC 104 but not the leuprolide group. Total productivity also significantly (P < or = 0.05) improved in both groups at 6 and 18 months. DMPA-SC 104 reduces endometriosis-associated pain as effectively as leuprolide and improves productivity with significantly less BMD decline.
    Preview · Article · May 2006 · Human Reproduction
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    ABSTRACT: To compare the efficacy and safety of SC depot medroxyprogesterone acetate (DMPA-SC 104) with that of leuprolide acetate in treatment of endometriosis. Phase 3, multicenter, randomized, evaluator-blinded, comparator-controlled trial. Clinical trial sites in Canada and United States. Two hundred seventy-four women with surgically diagnosed endometriosis. Intramuscular injections of DMPA-SC (104 mg) or leuprolide acetate (11.25 mg), given every 3 months for 6 months, with 12 months of posttreatment follow-up. Reduction in five endometriosis symptoms or signs (dysmenorrhea, dyspareunia, pelvic pain, pelvic tenderness, pelvic induration); change in bone mineral density (BMD), hypoestrogenic symptoms, bleeding, and weight. The depot medroxyprogesterone acetate given SC was statistically equivalent to leuprolide in reducing four of five endometriosis symptoms or signs at the end of treatment (month 6) and in reducing all five symptoms after 12 months' follow-up (month 18). Patients in the DMPA-SC 104 group showed significantly less BMD loss than did leuprolide patients at month 6, with scores returning to baseline at 12 months' follow-up. No statistically significant differences in median weight changes were observed between groups. Compared with leuprolide, DMPA-SC 104 was associated with fewer hypoestrogenic symptoms but more irregular bleeding. Efficacy of DMPA-SC 104 was equivalent to that of leuprolide for reducing endometriosis-associated pain, with less impact on BMD and fewer hypoestrogenic side effects but more bleeding.
    No preview · Article · Mar 2006 · Fertility and sterility
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    ABSTRACT: The objective was to develop recommendations for the diagnosis and treatment of endometriosis and its associated symptoms. A working group was convened comprised of practising gynaecologists and experts in evidence-based medicine from Europe, as well as an endometriosis self-help group representative. After reviewing existing evidence-based guidelines and systematic reviews, the expert panel met on three occasions for a day during which the guideline was developed and refined. Recommendations based solely on the clinical experience of the panel were avoided as much as possible. The entire ESHRE Special Interest Group for Endometriosis and Endometrium was given the opportunity to comment on the draft guideline, after which it was available for comment on the ESHRE website for 3 months. The working group then ratified the guideline by unanimous or near-unanimous voting; finally, it was approved by the ESHRE Executive Committee. The guideline will be updated regularly, and will be made available at http://www.endometriosis.org/guidelines.html with hyperlinks to the supporting evidence, and the relevant references and abstracts. For women presenting with symptoms suggestive of endometriosis, a definitive diagnosis of most forms of endometriosis requires visual inspection of the pelvis at laparoscopy as the 'gold standard' investigation. However, pain symptoms suggestive of the disease can be treated without a definitive diagnosis using a therapeutic trial of a hormonal drug to reduce menstrual flow. In women with laparoscopically confirmed disease, suppression of ovarian function for 6 months reduces endometriosis-associated pain; all hormonal drugs studied are equally effective although their side-effects and cost profiles differ. Ablation of endometriotic lesions reduces endometriosis-associated pain and the smallest effect is seen in patients with minimal disease; there is no evidence that also performing laparoscopic uterine nerve ablation (LUNA) is necessary. In minimal-mild endometriosis, suppression of ovarian function to improve fertility is not effective, but ablation of endometriotic lesions plus adhesiolysis is effective compared to diagnostic laparoscopy alone. There is insufficient evidence available to determine whether surgical excision of moderate-severe endometriosis enhances pregnancy rates. IVF is appropriate treatment especially if there are coexisting causes of infertility and/or other treatments have failed, but IVF pregnancy rates are lower in women with endometriosis than in those with tubal infertility. The management of severe/deeply infiltrating endometriosis is complex and referral to a centre with the necessary expertise is strongly recommended. Patient self-help groups can provide invaluable counselling, support and advice.
    Full-text · Article · Nov 2005 · Human Reproduction
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    ABSTRACT: Endometriosis is a chronic and recurrent disease characterized by the presence and proliferation of endometrial tissue outside the uterine cavity, which occurs in approximately 10% of women of reproductive age. In this estrogen-dependent disorder, lesions become inactive and gradually undergo regression during states of ovarian down-regulation, such as amenorrhoea or menopause. The impact of endometriosis includes impaired fertility potential, as well as symptoms of dysmenorrhoea, dyspareunia and chronic non-menstrual pain, all of which adversely affect quality of life. Management of endometriosis focuses on pain relief and includes medical and surgical treatment. Pharmacologic therapies currently in use include combination oral contraceptives (COCs), danazol, GnRH analogues and progestins. Although some agents show efficacy in relieving pain, all differ in their side effects, making it difficult to achieve a balance between efficacy and safety. Efficacy has been demonstrated with danazol or GnRH analogues; however, treatment is limited to 6 months because of significant metabolic side effects. Alternatives for longer-term management of symptoms include add-back therapy with GnRH analogues, COCs or progestins. Newer options for treatment of endometriosis include depot medroxyprogesterone acetate subcutaneous injection, as well as several agents under investigation that may prove to have therapeutic potential.
    Preview · Article · Sep 2005 · Human Reproduction Update
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    ABSTRACT: To investigate whether separated and cultured endometriotic and endometrial stromal and epithelial cells release urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), and soluble plasminogen activator receptor (suPAR) antigens in vitro. In vitro study. University hospital clinic. Regularly menstruating women with and without endometriosis. Tissue samples were collected at surgery performed for clinical reasons. The antigen concentrations of uPA, PAI-1, and suPAR in culture medium were assayed by enzyme-linked immunosorbent assay. Both stromal and epithelial cells from endometriotic and endometrial tissue released the three types of antigens, but the release of PAI-1 was significantly higher from stromal cells in the three types of tissue than from epithelial cells. Furthermore, the release of PAI-1 was significantly higher from endometriotic cells than from endometrial stromal cells. This study has demonstrated the basic capacity of separated epithelial and stromal cells from all three types of tissue to release uPA, PAI-1, and suPAR without any paracrine influence, as in vivo. The higher release of PAI-1 from endometriotic stromal cells might have importance for the invasive growth.
    No preview · Article · May 2005 · Fertility and Sterility
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    H Lettesjö · T Hansson · A Bergqvist · J Grönlund · A Dannaeus
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    ABSTRACT: Coeliac disease (CoD) is a small intestinal disorder characterized by villous atrophy, crypt cell hyperplasia and an increased production of T helper cell type 1 (Th1) cytokines. Interleukin (IL)-18 is a pro-inflammatory cytokine that has a crucial role in maintaining the Th1 response. In this study, the serum levels of IL-18 were measured in children with CoD or other gastrointestinal diseases in order to evaluate the possibility of using IL-18 as a disease activity marker. IL-18 levels were higher in samples from CoD patients [median 443 pg/ml (148-885)] compared to healthy controls [median 205 pg/ml (11-379)], P <0.05. In contrast, the levels of IL-18 were not enhanced significantly in the serum from patients with inflammatory bowel disease (IBD) [median 324 pg/ml (207-546)] or in the disease control group [median 303 pg/ml (2-689)]. In CoD patients, after 2 weeks of gluten challenge (GC), serum IL-18 was unchanged [median 268 pg/ml (59-458)] compared to patients on a gluten-free diet [median 220 pg/ml (53-600)], while IL-18 was increased after 12 weeks of GC [median 551 pg/ml (94-952)], P <0.01. The IL-18 levels correlated with IgA anti-transglutaminase antibody levels (rs=0.59, P=0.016) in serum from untreated CoD patients, and IL-18 also followed the degree of small intestinal villous atrophy in 12 out of 19 CoD patients. Our results support the view that serum IL-18 concentrations in children with CoD follow disease activity, suggesting a role for IL-18 in the induction of an inflammatory Th1-response after gluten exposure.
    Full-text · Article · Feb 2005 · Clinical & Experimental Immunology
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    ABSTRACT: The pathogenesis of endometriosis is presumed to be related to adhesion and invasion in ectopic sites of dispersed shed endometrium. The mechanism is poorly understood. The aim of this project was to investigate the role of the plasminogen-activating system (PAs), including urokinase plasminogen activator (uPA), urokinase plasminogen activator receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1), in the pathogenesis of endometriosis. The system is involved in tissue degradation and remodelling under both normal and pathological conditions. This project included the assay of the three proteins in tissue homogenates, localisation of both the proteins and their mRNA in tissue sections, and studies of their release in cell cultures. Our major findings were an up-regulation of mRNA for all three factors and higher concentrations of uPA, and PAI-1 in endometriotic and endometrial tissue from women with endometriosis compared to control endometrium. These findings might be of importance for menstrual shedding, adhesion, and invasion of viable endometrial fragments. The studies have shown above all that there is an important difference in the expression of the components of the PAs in endometrium from women with endometriosis compared to healthy endometrium, supporting the hypothesis that ectopic endometrial invasion takes place, at least partly, as a consequence of a disturbed fibrinolytic activity in the eutopic endometrium.
    No preview · Article · Sep 2004 · International Congress Series
  • Agneta Bergqvist · AnnaSofia Melin · Pär Sparén
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    ABSTRACT: The purpose of this study was to determine the risk of malignancies in a large cohort of patients with endometriosis through long-term follow-up. Results: This extensive Swedish national registry study comprising 64,492 women (766,556 person-years) diagnosed with endometriosis between 1969 and 2000, and followed for a mean of 12.7 years, showed a significantly increased risk of ovarian cancer, other endocrine types of cancer (i.e. in the adrenals, parathyroid glands, thymus, the pituitary gland, and pancreas), non-Hodgkin's lymphoma, and brain tumours. The risk of ovarian cancer was highest in women with ovarian endometriosis, but was also increased in women with other types of endometriosis; the risk was reduced in women with adenomyosis. Women with a hysterectomy before or at the same time as the endometriosis diagnosis had no increased risk of ovarian cancer. The risk of cervical cancer was reduced. Conclusion: Women with endometriosis have an increased risk of certain types of malignancy, in particular ovarian cancer. Hysterectomy appears to have a preventive effect.
    No preview · Article · Sep 2004 · International Congress Series
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    C Bruse · D Radu · A Bergqvist
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    ABSTRACT: Endometriotic tissue grows invasively. The plasminogen-activating system is suggested to participate in degradation of extracellular matrix (ECM) and modulation of cell adhesion and migration. We have previously demonstrated elevated levels of the fibrinolytic factors urokinase plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1) in endometriotic tissue and endometrium from women with endometriosis. The aim of the present study was to localize the uPA, PAI-1 and urokinase plasminogen activator receptor (uPAR) mRNA in endometriotic tissue and in endometrium both from women with and without endometriosis. With in situ hybridization, we found that uPA mRNA seems to be up-regulated in endometriotic glands and endometrial stroma as well as PAI-1 mRNA in endometriotic and endometrial stroma from women with endometriosis. uPAR mRNA likewise appears to be up-regulated in both glands and stroma in endometriotic tissue and in endometrial glands from patients compared to endometrial glands and stroma from healthy women. These differences might be important for menstrual shedding and adherence of endometrial fragments to peritoneal lining in women developing endometriosis and for the invasive growth of endometriotic tissue.
    Preview · Article · Apr 2004 · Molecular Human Reproduction
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    ABSTRACT: We have investigated whether there are any differences in the release of urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) from cultured endometrial and endometriotic stromal cells, and whether the release is regulated by epidermal growth factor (EGF) or transforming growth factor beta1 (TGFbeta1). The cells were isolated from endometriomas and endometrium from women with and without endometriosis. After treatment with EGF or TGF and in untreated controls, incubated media collected at 0, 24, 48 and 72 h were analyzed by ELISA. Stromal cells from all three types of tissues released uPA and PAI-1, but the soluble receptor of uPA was not measurable in any group. The basal release of uPA and PAI-1 from endometriotic cells was higher than from endometrial cells. The uPA release in endometriotic cells was reduced with and without the addition of EGF (p < 0.05) or TGFbeta1 (p < 0.05). EGF increased the release of PAI-1 from stromal cells from women without endometriosis (p < 0.05) but decreased the release of PAI-1 from stromal cells from endometriotic women (p < 0.05). TGFbeta1 increased the release of PAI-1 from endometriotic cells (p < 0.05) but had no effect in endometrial cells.
    No preview · Article · Mar 2003 · Gynecologic and Obstetric Investigation
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    ABSTRACT: To investigate whether endometriotic stromal cells release the urokinase plasminogen activator, soluble urokinase plasminogen activator receptor and plasminogen activator inhibitor-1. If so, to establish if there are any differences between endometrial stromal cells from women with and without endometriosis, and whether the release is hormonally regulated. Biopsies were obtained from endometriotic tissue and from endometrium from women with and without endometriosis. Stromal cells were isolated, incubated and treated with estradiol-17beta, progesterone or raloxifen. Incubation media collected at 0, 24, 48 and 72 h were analyzed by enzyme-linked immunosorbent assay. All these types of stromal cells released the urokinase plasminogen activator, soluble urokinase plasminogen activator receptor and urokinase plasminogen inhibitor-1. There was a significantly higher release of urokinase plasminogen inhibitor-1 and lower release of urokinase plasminogen activator and soluble urokinase plasminogen activator receptor in endometriotic cells. The release of urokinase plasminogen activator from endometrial stromal cells decreased during the study period both in control cultures and in cultures treated with progesterone or estradiol-17beta, but not in cultures treated with raloxifen nor in endometriotic cultures. The given hormones did not influence the release of the soluble urokinase plasminogen activator receptor. Progesterone significantly increased the urokinase plasminogen inhibitor-1 release in endometrial cells from both patient categories, and raloxifen significantly reduced the urokinase plasminogen inhibitor-1 release from stromal cells from both tissue categories from endometriotic patients. Estradiol-17beta had no effect. This study shows that stromal cells from endometrium and endometriotic tissues release the urokinase plasminogen activator, soluble urokinase plasminogen activator receptor and urokinase plasminogen inhibitor-1. The release is partly hormonally regulated, but differently in endometriotic than in endometrial cells.
    No preview · Article · Jun 2002 · Acta Obstetricia Et Gynecologica Scandinavica

Publication Stats

3k Citations
242.09 Total Impact Points

Institutions

  • 1988-2015
    • Karolinska Institutet
      • • Department of Medical Epidemiology and Biostatistics
      • • Department of Obstetrics and Gynecology
      • • Aging Research Center - ARC
      Сольна, Stockholm, Sweden
  • 2004-2008
    • Danderyds Sjukhus AB
      Tukholma, Stockholm, Sweden
  • 2005
    • Turku University Hospital
      Turku, Varsinais-Suomi, Finland
  • 1997-2005
    • Karolinska University Hospital
      • Department of Obstetrics and Gynecology
      Tukholma, Stockholm, Sweden
  • 2002
    • Universitair Ziekenhuis Leuven
      Louvain, Flemish, Belgium
  • 2001-2002
    • Akademiska Sjukhuset
      Uppsala, Uppsala, Sweden
    • Stockholm County Council
      Tukholma, Stockholm, Sweden
  • 1998
    • Malmö University
      Malmö, Skåne, Sweden
  • 1981-1993
    • Lund University
      • • Department of Obstetrics and Gynecology
      • • Department of Surgery
      Lund, Skåne, Sweden
  • 1984
    • IT University of Copenhagen
      København, Capital Region, Denmark