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| 14. |
- Chaireti, Roza, et al.
(författare)
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Endogenous thrombin potential is higher during the luteal phase than during the follicular phase of a normal menstrual cycle
- 2013
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Ingår i: Human Reproduction. - : Oxford University Press (OUP): Policy B1 - Oxford Open Option B. - 0268-1161 .- 1460-2350. ; 28:7, s. 1846-1852
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Tidskriftsartikel (refereegranskat)abstract
- Do thrombin generation and haemostatic parameters differ during the two phases of the menstrual cycle? less thanbrgreater than less thanbrgreater thanTotal thrombin concentration is higher during the luteal phase compared with the follicular phase of the menstrual cycle. less thanbrgreater than less thanbrgreater thanThe coagulation cascade is affected by many variables, such as fluctuations in the levels of sex hormones. The studies on the variations in haemostatic parameters during the menstrual cycle have produced diverse results. less thanbrgreater than less thanbrgreater thanThrombin generation and selected haemostatic parameters (fibrinogen, factor II, factor VII, factor VIII, factor X, von Willebrand factor, antithrombin and D-dimer) were measured during the two phases of a normal menstrual cycle in 102 healthy women not taking any form of hormone medication. less thanbrgreater than less thanbrgreater thanThe study cohort consisted of 102 healthy women with regular menstrual cycles. Thrombin generation was measured by the calibrated automated thrombogram method. Progesterone and sex hormone-binding globulin were measured by chemiluminescence enzyme immunoassays. Estradiol was measured by a sensitive radioimmunoassay. Fibrinogen was measured by a clotting method, antithrombin was measured by a chromogenic method and factor II, factor VII, factor VIII, factor X, von Willebrand factor and D-dimer were measured by photometric methods. less thanbrgreater than less thanbrgreater thanIt was shown that the total amount of generated thrombin (Endogenous Thrombin Potential) was significantly higher during the luteal compared with the follicular phase (P 0.027). Factor X was significantly higher during the follicular phase (P 0.028). Progesterone exhibited significant associations (measured by the least squares regression analysis) with fibrinogen and factor X during the follicular phase (P 0.043 and P 0.033, respectively) and with factors II and VII during the luteal phase (P 0.034 and P 0.024, respectively). The validity of the results from the regression analysis was further confirmed by performing correlation analyses (Pearson correlation matrix) for haemostatic markers for the luteal and follicular phases (accepted correlation level 0.8). less thanbrgreater than less thanbrgreater thanThe wide confidence interval for the differences in endogenous thrombin potential during the two phases could imply that the size of the cohort may not be sufficient to fully evaluate the biological variations. Additionally, the haemostatic markers were not shown to have significant associations with thrombin generation, suggesting that the increased thrombin concentration during the luteal phase would be mediated by another mechanism, as yet unidentified. less thanbrgreater than less thanbrgreater thanThe associations between progesterone and the haemostatic markers, as shown for both phases of the menstrual cycle, suggest a previously unknown or undefined yet potentially significant role for progesterone in the coagulation system. However, it has been shown that the use of progestogen-only preparations does not affect the coagulation system, which is partly the reason why they are considered safe for women with thrombophilia or previous thrombotic event. Further studies are required in order to demonstrate whether our results can be extrapolated for synthetic progestins, which might have significant implication on the indications for their use. less thanbrgreater than less thanbrgreater thanThis study was supported by the Karolinska Institutet, Linkping University and the County Council of stergtland. The authors report no conflicts of interest.
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| 15. |
- Cluff, AH, et al.
(författare)
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Prolonged labour associated with lower expression of syndecan 3 and connexin 43 in human uterine tissue
- 2006
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Ingår i: Reproductive Biology and Endocrinology. - : Springer Science and Business Media LLC. - 1477-7827. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prolonged labour is associated with greater morbidity and mortality for mother and child. Connexin 43 is a major myometrial gap junction protein found in human myometrium. Syndecan 3 seems to prevail in the human uterus among heparan sulphate proteoglycans, showing the most significant increase during labour. The aims of the present study were to investigate syndecan 3 and connexin 43 mRNA expressions and protein distributions in human uterine tissue during normal and prolonged labour. Methods: Uterine isthmic biopsies were collected from non-pregnant (n = 7), term pregnant women not in labour (n = 14), in normal labour (n = 7) and in prolonged labour (n = 7). mRNA levels of syndecan 3 and connexin 43 were determined by real time RT-PCR. The localization and expression were demonstrated by immunohistochemistry and confocal microscopy. Results: In women with prolonged labour, the mRNA expressions of syndecan 3 and Connexin 43 were considerably lower than the expression level at normal labour (p < 0.05). In term-pregnant tissue, the expression of syndecan 3 and connexin 43 did not differ significantly compared to nonpregnant and normal labour. The immunoreactivity of syndecan 3 was strong at normal labour, in contrast to prolonged labour, where both a weaker expression and an irregular distribution were detected. The immunoreactivity of connexin 43 increased until term and further stronger staining occurred at normal labour. At prolonged labour, the immunoreactivity was weaker and more unevenly distributed. At labour, a co-localization of syndecan 3 and connexin 43 could be demonstrated in the smooth muscle by confocal microscopy. Conclusion: The high expression of syndecan 3 and connexin 43 and their co-localization to the smooth muscle bundles during normal labour, together with the significant reduction in prolonged labour, may indicate a role for these proteins in the co-ordination of myometrial contractility.
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| 16. |
- Dubicke, A., et al.
(författare)
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Different secretion patterns of matrix metalloproteinases and IL-8 and effect of corticotropin-releasing hormone in preterm and term cervical fibroblasts
- 2008
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Ingår i: Molecular Human Reproduction. - : Oxford University Press (OUP). - 1460-2407 .- 1360-9947. ; 14:11, s. 641-647
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Tidskriftsartikel (refereegranskat)abstract
- The aims of the present study were to compare the levels of mRNA and protein expression of matrix metalloproteinase (MMP)-1, -3, -8 and -9 in human cervical tissue in preterm and term labor as well as not in labor and to determine if corticotropin-releasing hormone (CRH) has an effect on MMP-1, -3 and interleukin (IL)-8 secretion in both preterm and term cervical fibroblasts. Cervical biopsies were taken from 60 women: 18 at preterm labor, 7 at preterm not in labor, 18 at term labor and 17 at term not in labor. ELISA and Immulite were used for protein and real-time RT-PCR for mRNA analysis. Cervical fibroblast cultures were incubated for 18 h with different CRH concentrations (10(-13)-10(-6) M). The mRNA expression of MMP-1, -3 and -9 was higher in laboring groups compared with term not in labor. Protein levels of MMP-8 and -9 were higher in term in labor group compared with non-laboring groups. There were no significant differences in mRNA and protein expression between the preterm and respective term control groups. CRH significantly increased secretion of IL-8 in preterm and term cervical fibroblasts compared with controls. The secretion of IL-8 and MMP-1 was significantly higher and MMP-3 secretion lower in preterm cervical fibroblasts. In conclusion, cervical ripening at preterm seems to be a similar inflammatory process as at term with CRH involved. However, preterm and term cervical fibroblasts might have different phenotypes based on different secretion patterns of IL-8, MMP-1 and MMP-3.
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| 21. |
- Giwercman, YL, et al.
(författare)
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Response to treatment in patients with partial androgen insensitivity due to mutations in the DNA-binding domain of the androgen receptor
- 2000
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Ingår i: Hormone research. - : S. Karger AG. - 0301-0163. ; 53:2, s. 83-88
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Tidskriftsartikel (refereegranskat)abstract
- The androgen insensitivity syndrome is a disorder caused by deficient function of the androgen receptor, characterized by varying degrees of undermasculinization in karyotypic males. We have identified four mutations in the androgen receptor gene, in the region encoding the DNA-binding domain of the protein. Two mutations, R607X and R615G, were found in patients with complete insensitivity to androgens, whereas the other two, S578T and A596T, were found in patients with partial insensitivity. The functional consequences of the three missense mutations were assayed in vitro after transient expression of the receptors in COS cells. All mutants showed normal androgen binding but abnormal abilities to stimulate transcription of an androgen-responsive reporter gene. R615G abolished transactivation whereas S578T and A596T were partially malfunctional. The function of A596T, but not of S578T, was normalized at high androgen concentrations in vitro, reflecting the in vivo situation. Thus, patients with specific mutations in the DNA-binding domain of the androgen receptor may benefit from androgen treatment.
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| 26. |
- Lalitkumar, PGL, et al.
(författare)
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Effects of Estradiol/Micronized Progesterone vs. Conjugated Equine Estrogens/Medroxyprogesterone Acetate on Breast Cancer Gene Expression in Healthy Postmenopausal Women
- 2023
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 24:4
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies suggest estradiol (E2)/natural progesterone (P) confers less breast cancer risk compared with conjugated equine estrogens (CEE)/synthetic progestogens. We investigate if differences in the regulation of breast cancer-related gene expression could provide some explanation. This study is a subset of a monocentric, 2-way, open observer-blinded, phase 4 randomized controlled trial on healthy postmenopausal women with climacteric symptoms (ClinicalTrials.gov; EUCTR-2005/001016-51). Study medication was two 28-day cycles of sequential hormone treatment with oral 0.625 mg CEE and 5 mg of oral medroxyprogesterone acetate (MPA) or 1.5 mg E2 as percutaneous gel/day with the addition of 200 mg oral micronized P. MPA and P were added days 15–28/cycle. Material from two core-needle breast biopsies in 15 women in each group was subject to quantitative PCR (Q-PCR). The primary endpoint was a change in breast carcinoma development gene expression. In the first eight consecutive women, RNA was extracted at baseline and after two months of treatment and subjected to microarray for 28856 genes and Ingenuity Pathways Analysis (IPA) to identify risk factor genes. Microarray analysis showed 3272 genes regulated with a fold-change of >±1.4. IPA showed 225 genes belonging to mammary-tumor development function: 198 for CEE/MPA vs. 34 for E2/P. Sixteen genes involved in mammary tumor inclination were subject to Q-PCR, inclining the CEE/MPA group towards an increased risk for breast carcinoma compared to the E2/P group at a very high significance level (p = 3.1 × 10−8, z-score 1.94). The combination of E2/P affected breast cancer-related genes much less than CEE/MPA.
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| 27. |
- Landstrom, U, et al.
(författare)
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Effect on truck drivers' alertness of a 30-min. exposure to bright light: a field study
- 2004
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Ingår i: Perceptual and motor skills. - : SAGE Publications. - 0031-5125 .- 1558-688X. ; 98:33 Pt 1, s. 770-776
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Tidskriftsartikel (refereegranskat)abstract
- Reduced alertness is common during night driving. Light treatment may constitute one countermeasure to reduce sleepiness. To test this idea six professional drivers participated in this study in which they self-administered a 30-min. light treatment during a break in the middle of a night drive of about 9 hours. Two experimental conditions were used, including light exposures with a light box and a light visor. There was a control condition. Alertness was measured on a 100-mm visual analogue scale. No significant effect of light was found, but ratings of sleepiness increased significantly through the night drive. The experimental light treatment was not correlated with any increased wakefulness compared to the drivings where no extra light exposures were carried out.
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| 29. |
- Lind, PA, et al.
(författare)
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Efficacy of preoperative radiochemotherapy in patients with locally advanced pancreatic carcinoma
- 2008
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 47:3, s. 413-420
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Tidskriftsartikel (refereegranskat)abstract
- Background. The optimal care for patients with unresectable, non-metastatic pancreatic adenocarcinoma (PAC) is debated. We treated 17 consecutive cases with preoperative radiochemotherapy (RCT) as a means for downstaging their tumours and compared outcome with 35 patients undergoing direct surgery for primarily resectable PAC during the same time period. Methods. The patients had biopsy proven, unresectable, non-metastatic PAC which engaged >/=50% of the circumference of a patent mesenteric/portal vein for a distance >/=2 cm and/or <50% of the circumference of a central artery for <2 cm. The preop therapy included two courses of Xelox (oxaliplatin 130 mg/m(2) d1; capecitabine 2 000 mg/m(2) d1-14 q 3 w) followed by 3-D conformal radiotherapy (50.4 Gy; 1.8 Gy fractions) with reduced Xelox (d1-5 q 1 w X 6). Results. No incident of RCT-related CTC Grade 3-4 haematologic and six cases of non-haematologic side-effects were diagnosed. Sixteen patients completed the RCT and were rescanned with CT and reevaluated for surgery 4 weeks post-RCT. Five cases were diagnosed with new metastases to the liver. Eleven patients were accepted for surgery whereof eight underwent a curative R(0)-resection. The median overall survival for the latter group was 29 months, which compared favourably with our control group of patients undergoing direct curative surgery for primarily resectable PAC (median OS: 16 months; R(O)-rate: 75%). Perioperative morbidity was similar in the two cohorts but the duration of surgery was longer (576 vs. 477 min) and the op blood loss was greater (3288 vs. 1460 ml) in the RCT-cohort (p < 0.05). The 30-day mortality was zero in both groups. Conclusion. Preoperative RCT in patients with locally advanced PAC resulted in a high rate of curative resections and promising median survival in our treatment series. This trimodality approach merits further exploration in new studies, which are currently underway at our Department.
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| 33. |
- Norman, M., et al.
(författare)
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Association of Maternal SARS-CoV-2 Infection in Pregnancy With Neonatal Outcomes
- 2021
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Ingår i: Jama-Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 325:20, s. 2076-2086
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The outcomes of newborn infants of women testing positive for SARS-CoV-2 in pregnancy is unclear. OBJECTIVE To evaluate neonatal outcomes in relation to maternal SARS-CoV-2 test positivity in pregnancy. DESIGN, SETTING, AND PARTICIPANTS Nationwide, prospective cohort study based on linkage of the Swedish Pregnancy Register, the Neonatal Quality Register, and the Register for Communicable Diseases. Ninety-two percent of all live births in Sweden between March 11, 2020, and January 31, 2021, were investigated for neonatal outcomes by March 8, 2021. Infants with malformations were excluded. Infants of women who tested positive for SARS-CoV-2 were matched, directly and using propensity scores, on maternal characteristics with up to 4 comparator infants. EXPOSURES Maternal test positivity for SARS-CoV-2 in pregnancy. MAIN OUTCOMES AND MEASURES In-hospital mortality; neonatal resuscitation; admission for neonatal care; respiratory, circulatory, neurologic, infectious, gastrointestinal, metabolic, and hematologic disorders and their treatments; length of hospital stay; breastfeeding; and infant test positivity for SARS-CoV-2. RESULTS Of 88 159 infants (49.0% girls), 2323 (1.6%) were delivered by mothers who tested positive for SARS-CoV-2. The mean gestational age of infants of SARS-CoV-2-positive mothers was 39.2 (SD, 2.2) weeks vs 39.6 (SD, 1.8) weeks for comparator infants, and the proportions of preterm infants (gestational age <37 weeks) were 205/2323 (8.8%) among infants of SARS-CoV-2-positive mothers and 4719/85 836 (5.5%) among comparator infants. After matching on maternal characteristics, maternal SARS-CoV-2 test positivity was significantly associated with admission for neonatal care (11.7% vs 8.4%; odds ratio [OR], 1.47; 95% CI, 1.26-1.70) and with neonatal morbidities such as respiratory distress syndrome (1.2% vs 0.5%; OR, 2.40; 95% CI, 1.50-3.84), any neonatal respiratory disorder (2.8% vs 2.0%; OR, 1.42; 95% CI, 1.07-1.90), and hyperbilirubinemia (3.6% vs 2.5%; OR, 1.47; 95% CI, 1.13-1.90). Mortality (0.30% vs 0.12%; OR, 2.55; 95% CI, 0.99-6.57), breastfeeding rates at discharge (94.4% vs 95.1%; OR, 0.84; 95% CI, 0.67-1.05), and length of stay in neonatal care (median, 6 days in both groups; difference, 0 days; 95% CI, -2 to 7 days) did not differ significantly between the groups. Twenty-one infants (0.90%) of SARS-CoV-2-positive mothers tested positive for SARS-CoV-2 in the neonatal period; 12 did not have neonatal morbidity, 9 had diagnoses with unclear relation to SARS-CoV-2, and none had congenital pneumonia. CONCLUSIONS AND RELEVANCE In a nationwide cohort of infants in Sweden, maternal SARS-CoV-2 infection in pregnancy was significantly associated with small increases in some neonatal morbidities. Given the small numbers of events for many of the outcomes and the large number of statistical comparisons, the findings should be interpreted as exploratory.
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| 35. |
- Tornblom, SA, et al.
(författare)
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15-Hydroxyprostaglandin dehydrogenase and cyclooxygenase 2 messenger ribonucleic acid expression and immunohistochemical localization in human cervical tissue during term and preterm labor
- 2004
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 89:6, s. 2909-2915
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Tidskriftsartikel (refereegranskat)abstract
- Here we have examined the enzymes cyclooxygenase (COX)-2 and 15-hydroxyprostaglandin dehydrogenase (15-OH PGDH) in pregnant human cervix. In biopsies taken transvaginally after preterm and term elective cesarean sections and vaginal deliveries, the levels of mRNA coding for COX-2 and 15-OH PGDH were assessed by Northern blotting. The cellular localization of the COX-2 and 15-OH PGDH proteins was determined by immunohistochemical analysis. COX-2 and 15-OH PGDH mRNAs were expressed at detectable levels in the cervical biopsies from all four groups of subjects. At cesarean sections ( unripe cervix), the level of 15-OH PGDH mRNA was significantly higher than the level in the ripe cervix at the time of partus, irrespective of the gestational length. In contrast, the level of COX-2 mRNA was similar in all subjects. Immunoreactivity of COX-2 and 15-OH PGDH was expressed by activated fibroblasts. The present investigation documents the expression and cellular localization of COX-2 and 15-OH PGDH in the preterm and term pregnant human cervix. This observation indicates that both preterm and term cervical ripening is associated with decreased degradation of prostaglandins.
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| 37. |
- Tornblom, SA, et al.
(författare)
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MRNA expression and localization of bNOS, eNOS and iNOS in human cervix at preterm and term labour
- 2005
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Ingår i: Reproductive Biology and Endocrinology. - : Springer Science and Business Media LLC. - 1477-7827. ; 3:33
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Tidskriftsartikel (refereegranskat)abstract
- Background: Preterm birth is the primary cause of the neonatal mortality and morbidity. There will be no preterm birth without a cervical softening. Nitric oxide ( NO) is shown to be a mediator of term cervical ripening. The aim of this study was to investigate mRNA expression of the three isomers of NO synthases ( NOS) and to identify them by immunohistochemistry in the human cervix at preterm birth compared to term. Methods: The three isomers of NOS- inducible ( iNOS), endothelial ( eNOS) and neuronal ( bNOS) - were investigated in the human cervix. The expression of mRNA was determined using RealTime Multiplex RT- PCR. The localisation of synthases in the cervical tissue was analysed using immunohistochemistry. Cervical biopsies were obtained from 4 groups of women without clinical signs of infection: preterm ( PTL), term labour ( TL), preterm not in labour ( PTnotL) and term not in labour ( TnotL) patients. One- Way ANOVA, Kruskal- Wallis, Student t- test or Mann- Whitney test were applied as appropriate to determine statistically significant differences among the groups. Results: Patients in preterm labour had significantly ( p < 0.01) higher mRNA levels of all the three NOS isomers compared to those in term labour. Women not in labour, irrespective of gestational age, thus with unripe cervices, had significantly lower eNOS mRNA levels compared to those in labour ( p < 0.01). Immunoreactivity for all three NO synthases was observed in each examined sample in all groups. The bNOS staining was the most prominent. Conclusion: The mRNA levels were higher in the preterm labour group compared to the women at term labour. The significant increase of the eNOS mRNA expression, from the unripe to the favourable cervical state during labour, may indicate a role of eNOS and supports the role of NO in the cervical ripening process. All the three synthases were identified by immunohistochemistry in all the groups of study.
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| 42. |
- Westergren Soderberg, M, et al.
(författare)
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Young women with genital prolapse have a low collagen concentration
- 2004
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 83:12, s. 1193-1198
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Tidskriftsartikel (refereegranskat)abstract
- Background. Genital prolapse is a common and handicapping form of pelvic floor dysfunction. To explain its genesis as a result of endopelvic connective tissue weakness, the collagen state was analyzed in women with and without genital prolapse. Methods. Punch biopsies from the paraurethral ligaments were obtained during the operation from 22 women undergoing surgery for genital prolapse. As controls, similar biopsies were taken from 13 women who underwent gynecologic surgery for other benign reasons. Collagen concentration as hydroxyproline and its extractability by pepsin digestion were studied in relation to age by multiple regression, two-way ANOVA, Levene's test, and Student's t-test. Histological examination was also performed. Results. Women, younger than 53 years, with genital prolapse had a 30% lower collagen concentration than age-matched controls, which reached significance, P = 0.01. The extractability by pepsin digestion, an indicator of cross-links in the collagen molecule, did not significantly differ between groups. It did, however, decrease significantly with age in both prolapse patient and control groups. Morphology supported these findings with a less-dense extracellular matrix composition subepithelially in genital prolapse compared to a healthy control. Conclusion. For the first time, we show that young women with genital prolapse have a decreased collagen concentration, suggesting a different organization of the endopelvic connective tissue extracellular matrix. Furthermore, these alterations differ from those earlier found in younger women with stress urinary incontinence.
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