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Biomedical subjects

A Bergqvist

Publications and source records attributed to A Bergqvist.

At least 19 recordsLinked to original sources
PubMed2006

Treatment with anti-TNF monoclonal antibody (c5N) reduces the extent of induced endometriosis in the baboon.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Animals↗
PubMed2006

Endometriosis and the risk of cancer with special emphasis on ovarian cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adolescent↗
PubMed2005

Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain.

BACKGROUND: A clinical study compared efficacy and safety of depot medroxyprogesterone acetate (DMPA) with leuprolide for endometriosis-associated pain. METHODS: 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. RESULTS: 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. CONCLUSIONS: DMPA-SC 104 reduces endometriosis-associated pain as effectively as leuprolide and improves productivity with significantly less BMD decline.

Administration, Cutaneous↗
PubMed2005

Enhanced interleukin-18 levels in the peripheral blood of children with coeliac disease.

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.

Adolescent↗
PubMed2004

In situ localization of mRNA for the fibrinolytic factors uPA, PAI-1 and uPAR in endometriotic and endometrial tissue.

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.

Endometriosis↗
PubMed2001

Interleukin 1beta, interleukin-6, and tumor necrosis factor-alpha in endometriotic tissue and in endometrium.

OBJECTIVE: To compare the levels of IL-1beta, IL-6, and TNFalpha in endometriotic tissue and in endometrium from women with endometriosis and healthy controls. DESIGN: Open. SETTING: Department of Obstetrics and Gynecology at a university hospital. PATIENT(S): Twenty-six women with endometriosis and 22 controls operated on for clinical indications. INTERVENTION(S): ELISA in homogenized tissue samples collected during surgery. MAIN OUTCOME MEASURE(S): Levels of IL-1beta, IL-6, and TNFalpha in tissue homogenates. RESULT(S): The three types of tissue differed significantly with respect to all three cytokines. Endometriotic tissue had significantly higher concentrations of IL-1beta than endometrium from both patients with endometriosis and healthy controls. Both endometriotic tissue and endometrium from patients had significantly higher concentrations of IL-6, and endometriotic tissue had significantly lower concentration of TNFalpha than did endometrium from controls. IL-1beta showed a cycle phase dependence that was significant in endometrium from patients, being higher in the secretory than in the follicular phase. IL-1beta was significantly higher in endometrioma than in lesions of other localizations. Concentrations of IL-1beta and IL-6 were positively correlated in endometriotic tissue and in endometrium from controls. No other significant correlations were found. CONCLUSION(S): This study has shown a significant production of IL-1beta, IL-6, and TNFalpha in endometriotic tissue and endometrium, with significant differences between the tissue types, indicating a deviating cytokine pattern in both endometriotic tissue and endometrium from women with endometriosis compared with that from healthy controls.

Endometriosis↗
PubMed2001

Reduced developmental potential in oocytes from women with endometriosis.

PURPOSE: To study retrospectively the outcome of intracytoplasmatic sperm injection (ICSI) in women with endometriosis compared with women with no known female infertility factor. METHODS: All couples treated with ICSI because of male infertility plus verified endometriosis (n = 26) and all couples treated with ICSI because of male infertility only (n = 125) during the period January 1995 to June 1999 were included. Data were collected from patient files and ICSI protocols. RESULTS: The time to complete down regulation was significantly longer (p = 0.0108), the dose of FSH significantly higher (0.0247), the day for oocyte pickup significantly later (p = 0.0091), and the cleavage rate of oocytes significantly lower (p = 0.0011) in women with endometriosis compared with controls. There was no significant difference in implantation rate or pregnancy rate between the groups. CONCLUSIONS: Women with endometriosis presented significantly reduced follicular response and oocyte cleavage rate, two mechanisms that might be related to a disturbed oogenesis.

Adult↗
PubMed2001

Transcriptional activation of the interleukin-2 promoter by hepatitis C virus core protein.

Most patients infected with hepatitis C virus (HCV) become chronic carriers. Viruses that efficiently establish persistent infections must have effective ways of evading host defenses. In the case of HCV, little is known about how chronic infections are established or maintained. Besides hepatocytes, several reports suggest that HCV can infect T and B lymphocytes. Since T cells are essential for viral clearance, direct or indirect effects of HCV on T-cell function could influence the outcome of infection. Given that T-cell growth and differentiation require the cytokine interleukin 2 (IL-2), we asked whether HCV might modulate synthesis of IL-2. Portions of the HCV polyprotein were expressed in Jurkat cells under a variety of conditions. We found that the highly conserved HCV core protein, in combination with other stimuli, was able to dramatically activate transcription from the IL-2 promoter. The carboxy-terminal hydrophobic portion of the core protein was required for this activity. Activation was dependent on nuclear factor of activated T cells (NFAT), occurred in cells deficient in the tyrosine kinase p56(lck), and could be blocked by addition of cyclosporin A and by depletion of calcium. These results suggest that the HCV core protein can activate transcription of the IL-2 promoter through the NFAT pathway. This novel activity may have consequences for T-cell development and establishment of persistent infections.

Calcium↗
PubMed2001

Changes in quality of life after hormonal treatment of endometriosis.

BACKGROUND: To assess whether hormonal treatment of endometriosis improves quality of life for women with endometriosis. METHODS: In a prospective, randomized, double-blind, double-dummy study on 48 women with verified endometriosis, the pain pattern and quality of life were registered before, during and after treatment with nafarelin or medroxyprogesterone acetate. The distribution of the studied parameters were tested by means of a Skewness test. ANOVA analysis was used for normally distributed variables and Friedman's analysis and Mann-Whitney U-test for non normally distributed variables. RESULTS: There was a difference between the 30 women who participated all through the study and the 18 who dropped out. It was noticeable that anxiety-depression and sleep disturbances were significantly more common among the drop outs. There was a significant reduction in symptom score during the study, without any significant difference between the treatment groups. The sleep disturbances and anxiety-depression score improved significantly from before treatment to the end of the follow-up, but the anxiety-depression score increased during the nafarelin treatment period. There was a statistically significant improvement of paid working life in the nafarelin treated group. All the other psycho-social parameters as well as emotional balance improved during the study period without difference between groups. CONCLUSION: When hormonal treatment is planned it is very important to take into consideration previous psychosocial experiences of the patient. Factors of importance for quality of life such as sleep disturbances and anxiety-depression improved significantly after treatment with nafarelin or medroxyprogesterone acetate.

Adolescent↗
PubMed2000

[Endometriosis--an inflammatory disease in women. Pain and reduced fertility are serious symptoms].

Endometriosis is a common disease with serious consequences for the patient and for society. Until now there has been no reliable method for diagnosing endometriosis besides direct visualization, e.g. utilizing laparoscopy. IVF offers the most successful treatment of endometriosis-related infertility, and a patient should be offered that treatment after one year of infertility. Waiting lists are often rather long, and other treatment modalities might be attempted while waiting for IVF. Pharmacological treatment does not increase the chances of pregnancy, while surgical extirpation of mild to moderate endometriosis might well result in a pregnancy earlier than anticipated.

Chronic Disease↗
PubMed2000

[Current aspects on the treatment of endometriosis].

The aim of pharmacological treatment of endometriosis is to reduce estrogen levels, which may be achieved using gestagens or GnRH-agonists. The effects of the different hormones are mainly the same, while side effects differ. If the GnRH-agonist dose is modified, or if a low dose of estrogen and/or gestagen is given in addition, the hypo-estrogenic side effects of GnRH-agonists can be reduced. Surgical treatment can often be performed in conjunction with diagnostic laparoscopy. Supplementary hormonal treatment may postpone recurrence. Because endometriosis is in many women a chronically recurring disorder, continuity in the doctor-patient relationship is essential.

Analgesics↗
PubMed2000

Elevated expression of tumour necrosis factor alpha in cultured granulosa cells from women with endometriosis.

Fertilization and oocyte cleavage rates have previously been demonstrated to be lower for women with endometriosis undergoing IVF compared with controls. This might be related to impaired oocyte function, possibly due to an inflammatory milieu in the pelvis of these women, where an elevated concentration of many cytokines is documented. The aim of this study was to examine whether granulosa cells from women with endometriosis deviated with respect to production of the inflammatory cytokines interleukin-1beta, interleukin-6, interleukin-8 and tumour necrosis factor alpha (TNFalpha) compared with granulosa cells from healthy women, undergoing IVF for male infertility. The effect of human chorionic gonadotrophin on cytokine production was also investigated. Granulosa cells in follicular fluid were obtained at oocyte retrieval for IVF. Incubated cell culture media were analysed by enzyme-linked immunosorbent assay. The basal production of all four cytokines was higher in cells from women with endometriosis when compared to controls, although the increase was only significant for TNFalpha. Chorionic gonadotrophin had no significant effect, although it had a tendency to suppress cytokine release in both patient categories. Whether aberrant cytokine production in granulosa cells from women with endometriosis may disturb fertilizing capacity of oocytes requires study.

Adult↗
PubMed2000

Production of interleukins 1beta, 6 and 8 and tumor necrosis factor alpha in separated and cultured endometrial and endometriotic stromal and epithelial cells.

The production of IL-1beta, IL-6, IL-8 and TNF-alpha was studied in short-time culture of separated stromal and epithelial cells. The cytokine secretion into culture medium was analyzed using immunoassay to evaluate the cytokine protein levels and bioassay to assess the bioactivity of the cytokines. Tissue samples of endometrium and ovarian endometriomas were obtained from 4 patients operated on for clinical reasons. Only IL-8 was found in all samples. IL-1beta and TNF-alpha were detected in the culture medium from most stromal cell samples, but in fewer media from epithelial cell samples. IL-6 was measurable in a few medium samples. Few of the samples displayed a bioactivity. There was no obvious difference between endometrium and endometriotic cell samples besides the production of IL-8 that seems to be lower in endometriotic tissue.

Adult↗
PubMed2000

A comparative study of the acceptability and effect of goserelin and nafarelin on endometriosis.

The effects of goserelin and nafarelin were compared in a prospective, randomized, open, parallel study of 6 months' treatment of 252 women with symptomatic, laparoscopically proven endometriosis. Twenty-eight departments of obstetrics and gynecology in Sweden, Norway, Denmark and Finland were included. Evaluations were made every 3 months for quantification of pain, bleeding and adverse events and convenience of treatment, and at 3 months after the end of treatment, when a control laparoscopy was performed for evaluation of changes in endometriotic lesion size, color and location. Thirty-nine patients withdrew and 113 women given goserelin and 100 women given nafarelin completed the study. There were no statistically significant differences between the groups, either in adverse events or in bleeding. There were no correlations between location, lesion size or type of lesion, and symptom score in either group, or between treatments with regard to change in endometriosis score. In both groups, the percentage of red and black lesions was reduced while the proportion of white lesions increased. The pain score was significantly reduced in both groups. Local irritation in the nasal mucosa was reported in both groups, mostly in the nafarelin-treated group. The goserelin-treated group also reported local symptoms at the injection site. We conclude that there is no statistically significant difference in treatment results or side-effects between goserelin and nafarelin when used for the treatment of endometriosis.

Administration, Intranasal↗
PubMed1999

Tenascin is differentially expressed in endometrium and endometriosis.

Endometriosis is characterized by the presence of functional endometrial tissue outside the uterine cavity, most commonly on the ovary and peritoneum. The aetiology of endometriosis is not understood, although the adhesion of endometrial cells to the extracellular matrix (ECM) would be expected to play a central role in its pathogenesis. The expression of ECM molecules in endometrium and in endometriosis has been investigated using immunohistochemistry and western blotting techniques. The ECM components collagen IV, laminin, vitronectin, and fibronectin had a similar pattern of expression throughout the menstrual cycle in endometrium and endometriosis. Expression of tenascin was elevated in the stroma of the functionalis region of the endometrium during the proliferative stage of the menstrual cycle and in endometriosis. Tenascin expression in endometriosis was not modulated according to the stage of the menstrual cycle. It is concluded that expression of tenascin is strictly regulated in endometrium and may be important in endometrial regeneration and in the pathogenesis of endometriosis.

Adult↗