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1.
  • Akhter, Tansim, 1967-, et al. (author)
  • Artery Wall Layer Dimensions during Normal Pregnancy : A longitudinal study using non-invasive high-frequency ultrasound
  • 2013
  • In: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 304:2, s. H229-H234
  • Journal article (peer-reviewed)abstract
    • The vascular effects of normal pregnancy were investigated by estimating the intima and media thicknesses of the common carotid artery separately using 22MHz ultrasound (Collagenoson, Meudt, Germany) in 57 healthy women with normal pregnancies and pregnancy outcomes, in all three trimesters and at one year postpartum. A thick intima, thin media and high intima/media (I/M) ratio are signs of a less healthy artery wall. The mean artery wall layer dimensions remained fairly constant during pregnancy but the intima thickness and I/M thickness ratio appeared to improve (decrease) postpartum (p<0.001 for both). The cardiovascular risk parameters age, body mass index (BMI), and blood pressure in the first trimester were associated with higher I/M ratios, especially in the second trimester, whereas higher serum estradiol levels were significantly associated with a lower I/M ratio. Changes from the first to second trimesters in I/M ratio, taking into account differential changes in intima and media thickness, were significantly (p<0.05-0.001) associated with all risk parameters tested except age, which was associated with increased intima thickness (p=0.02). Associations with third trimester values and changes from first to third trimesters were similar but less apparent. Thus, fairly constant mean artery wall layer dimensions during pregnancy appeared to improve postpartum. However, higher age, BMI or blood pressure, and lower serum estradiol levels in the first trimester appeared to negatively affect the artery wall, strongly suggesting that pregnancy has negative vascular effects in some women. A less likely explanation involves possible adaptation to physiological changes during and after pregnancy.
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2.
  • Akhter, Tansim, 1967-, et al. (author)
  • Association between angiogenic factors and signs of arterial aging in women with pre-eclampsia
  • 2017
  • In: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 50, s. 93-99
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: Pre-eclampsia (PE) is associated with an increased risk of cardiovascular disease (CVD) later in life. In PE there is a substantial increase in levels of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt1) and decreased levels of the pro-angiogenic factor placental growth factor (PlGF). Elevated levels of sFlt1 are also found in individuals with CVD. The aims of this study were to assess sFlt1, PlGF and the sFlt1/PlGF ratio and their correlation with signs of arterial aging by measuring common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE.METHODS: Serum sFlt1 and PlGF levels were measured using commercially available enzyme-linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high-frequency (22 MHz) ultrasonography in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, with reassessment one year postpartum. A thick intima, thin media and a high I/M ratio indicate a less healthy arterial wall.RESULTS: During pregnancy, higher levels of sFlt1, lower levels of PlGF and thicker intima, thinner media and higher I/M ratios were found in women with PE vs. controls (all p < 0.0001). Further, sFlt1 and the sFlt1/PlGF ratio were positively correlated with intima thickness and I/M ratio (all p < 0.0001), but negatively correlated with media thickness (p = 0.002 and 0.03, respectively). About one year postpartum, levels of sFlt1 and the sFlt1/PlGF ratio had decreased in both groups, but compared with controls women in the PE group still had higher levels (p = 0.001 and 0.02, respectively). Further, sFlt1 levels and the sFlt1/PlGF ratio were still positively correlated with intima thickness and I/M ratio.CONCLUSIONS: Higher sFlt1 levels and sFlt1/PlGF ratios in women with PE were positively associated with signs of arterial aging during pregnancy. About one year postpartum sFlt1 levels and the sFlt1/PlGF ratios were still higher in the PE group, and also associated with the degree of arterial aging.
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3.
  • Akhter, Tansim, 1967- (author)
  • Carotid Artery Wall Layer Dimensions during and after Pre-eclampsia : An investigation using non-invasive high-frequency ultrasound
  • 2013
  • Doctoral thesis (other academic/artistic)abstract
    • Pre-eclampsia is associated with increased risk of cardiovascular disease (CVD) later in life. The ‘gold standard’ for estimating cardiovascular risk - ultrasound assessment of the common carotid artery intima-media thickness (CCA-IMT) - does not convincingly demonstrate this increased risk. The aim of this thesis was to examine whether high-frequency (22 MHz) ultrasound assessment of the individual CCA intima and media layers and calculation of the intima/media (I/M) ratio - can indicate the increased cardiovascular risk after pre-eclampsia. After validation of the method in premenopausal women with systemic lupus erythematosus (SLE) who have a recognized increased risk of CVD, women during and after normal and preeclamptic pregnancies were investigated.Assessment of the individual artery wall layers reliably demonstrated the increased cardiovascular risk in premenopausal women with SLE, while CCA-IMT did not. The artery wall layer dimensions in women with SLE were comparable to those of postmenopausal women without SLE and were 30 years older.Among the women with normal pregnancies negative changes to the artery wall later on in the pregnancy were seen in those with lower serum estradiol, older age, higher body mass index or higher blood pressure early in the pregnancy. About one year postpartum, both the mean intima thickness and the I/M ratio had improved, compared to values during pregnancy. These findings support the theory that normal pregnancy is a stress on the vascular system.Women who developed pre-eclampsia (mean age 31 years) had thicker intima layers, thinner media layers and higher I/M ratios, both at diagnosis and one year postpartum, than women with normal pregnancies, indicating increased cardiovascular risk.Women with a history of severe pre-eclampsia (mean age 44 years; mean 11 years since the last delivery) had thicker intima layers and higher I/M ratios than women with a history of normal pregnancies, indicating long-standing negative vascular effects.Assessment of individual CCA wall layers, but not of CCA-IMT, provided clear evidence of the well-known increased cardiovascular risk in women with SLE or pre-eclampsia. The method has the potential to become an important tool in reducing cardiovascular morbidity and mortality in these women through early diagnosis and intervention.
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4.
  • Akhter, Tansim, et al. (author)
  • Changes in the Artery Wall Layer Dimensions in Women with Preeclampsia : an investigation using non-invasive high frequency ultrasound
  • 2012
  • In: Acta Obstetricia et Gynecologica Scandinavica. - 0001-6349 .- 1600-0412. ; 91:S159, s. 28-28
  • Journal article (other academic/artistic)abstract
    • Background:Preeclampsia (PE) is associated with increased risk for cardiovascular disease later in life. Whether, the artery wall layer dimensions differ between PE and normal pregnancy is unclear. The aim of this study was to estimate if women with PE have different common carotid artery wall layer dimensions than women with normal pregnancy, both during pregnancy and about one year postpartum.Methods:By using high-frequency (22MHz) ultrasound (Collagenoson, Meudt, Germany) separate estimates of the common carotid artery intima and media layers were obtained and the I/M ratio was calculated in women with PE (n=55 during pregnancy and n=48 at postpartum) and with normal pregnancy (n=65 during pregnancy and n=59 at postpartum). Thick intima, thin media and a high intima/media ratio are signs of less healthy artery wall and vice versa.Results:In women with PE, the intima was thicker (0.18 } 0.03 vs. 0.11 } 0.02; p < .001), the media was thinner (0.47 } 0.12 vs. 0.55 } 0.14; p = .001) and the I/M ratio was higher (0.41 } 0.14 vs. 0.20 } 0.05; p < .001) compared to women with normal pregnancy. Further, for changes from pregnancy to postpartum, both for PE and normal pregnancy, the intima and the I/M ratio had improved but still significantly higher in women with PE than in women with normal pregnancy.Conclusion:In women with PE, we found a thicker intima, thinner media and a higher I/M ratio compared to women with normal pregnancy, indicating a more negatively affected artery wall layer dimensions. Persisting negative effects of PE on artery wall at postpartum, despite improvement of artery wall layers compared to values during pregnancy, indicates a permanent damage of the vascular system in this group of women.
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6.
  • Akhter, Tansim, 1967-, et al. (author)
  • Dimethylarginines correlate to common carotid artery wall layer dimensions and cardiovascular risk factors in pregnant women with/without preeclampsia : A group comparative study
  • 2021
  • In: European Journal of Obstetrics, Gynecology, and Reproductive Biology. - : Elsevier. - 0301-2115 .- 1872-7654. ; 258, s. 288-293
  • Journal article (peer-reviewed)abstract
    • Objectives: Asymmetric- and symmetric dimethylarginines (ADMA, SDMA) are elevated in cardiovascular disease (CVD). Preeclampsia is a pregnancy-specific syndrome and is an independent risk factor for subsequent CVD. Aims were to investigate whether ADMA, SDMA levels and L-arginine/ADMA and I.arginine/SDMA ratios during pregnancy and their changes from pregnancy to postpartum are associated to arterial wall layer dimensions and cardiovascular risk factors in women with and without preeclampsia. Study design: Dimethylarginines were analyzed by LC-MS, and the common-carotid-artery (CCA) intima and media thicknesses were estimated using 22-MHz non-invasive ultrasonography in women with preeclampsia (cases = 48) and normal pregnancies (controls = 58) in similar gestational age, with reassessment one-year postpartum. A thick intima, thin media and high intima/media ratio (I/M) indicates a less healthy arterial wall. Results: The median age of cases and controls was 30 years. During pregnancy, women with preeclampsia had higher plasma ADMA, SDMA and lower t-arginine/ADMA and L-arginine/SDMA (all p <0.01) than women with normal pregnancies. Further, ADMA, SDMA, L-arginine/ADMA and L-arginine/SDMA correlated to intima thickness (r(s) = 0.33/0.33/-0.33/-0.35 and p <0.01), UM (r(s) = 0.26/0.28/-0.22/-0.26 and p <0.05) and mean arterial pressure (MAP) (rs = 0.43/0.42/-0.39/-0.40 and p <0.0001). Changes in ADMA, SDMA and t-arginine/SDMA from pregnancy to postpartum correlated to changes in intima thickness (r(s) = 0.22/0.32/-0.21 and p < 0.05/<0.01/<0.05), I/M (r(s) = 0.22/0.31/0.08 and p < 0.05/<0.01/=0.43) and MAP (r(s) = 0.31/0.53/-0.25 and p < 0.01/<0.001/<0.05). No correlations were found for conventional CCA intima-media-thickness. Conclusions: Dimethylarginines were associated to signs of adverse effects on arterial wall layer dimensions and cardiovascular risk factors in women with and without preeclampsia, during pregnancy and to their changes from pregnancy up to one-year postpartum. (C) 2021 The Authors. Published by Elsevier B.V.
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7.
  • Akhter, Tansim, 1967-, et al. (author)
  • Individual Common Carotid Artery Wall Layer Dimensions, but Not Carotid Intima-Media Thickness, Indicate Increased Cardiovascular Risk in Women With Preeclampsia : An investigation using non-invasive high-frequency ultrasound
  • 2013
  • In: Circulation Cardiovascular Imaging. - 1941-9651 .- 1942-0080. ; 6:5, s. 762-768
  • Journal article (peer-reviewed)abstract
    • Background Preeclampsia (PE) is associated with increased risk of cardiovascular disease later in life. Ultrasound assessment of the common carotid artery intima-media thickness (IMT) during or after PE has not indicated any increased cardiovascular risk. Methods and Results We used high-frequency ultrasound (22 MHz) to estimate the individual common carotid artery IMTs in 55 women at PE diagnosis and in 64 women with normal pregnancies at a similar stage. All were re-examined about 1 year postpartum. A thick intima, thin media, and high intima/media (I/M) ratio are signs of a less healthy artery wall. PE was associated with a significantly thicker mean common carotid artery intima, thinner media, and higher I/M ratio than in normal pregnancy (mean I/M difference, 0.21; 95% confidence interval, 0.17-0.25; P<0.0001). After adjustment for first trimester body mass index and mean arterial pressure, differences in intima thickness and I/M remained significant. About 1 year postpartum, these values had improved in both groups, but group differences remained significant (all adjusted P<0.0001). There were no significant differences in IMT between groups. In receiver-operating characteristic curve analysis, intima thickness and I/M were strongly predictive of prevalent PE (area under the curve, approximate to 0.95), whereas IMT was not (area under the curve, 0.49). Conclusions The arteries of women with PE were negatively affected during pregnancy and 1 year postpartum compared with women with normal pregnancies, indicating increased cardiovascular risk. Estimation of intima thickness and I/M ratio seem preferable to estimation of common carotid artery IMT in imaging cardiovascular risk in PE. Results from this pilot study warrant further confirmation.
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8.
  • Akhter, Tansim, 1967-, et al. (author)
  • Serum Pentraxin 3 is associated with signs of arterial alteration in women with preeclampsia.
  • 2017
  • In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 241, s. 417-422
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Preeclampsia (PE) in pregnancy is a state of exaggerated inflammation and is associated with an increased risk of cardiovascular disease (CVD) later in life. Levels of pentraxin 3 (PTX3), a novel inflammation marker, are increased during PE and in individuals with CVD. The primary aim of this study was to assess whether serum PTX3 in women with PE is associated with adverse arterial effects; a thicker intima and higher intima/media (I/M) ratio in the common carotid artery (CCA).METHODS: Serum PTX3 levels were measured using commercially available enzyme-linked immunosorbent assay kits, and individual CCA intima and media thicknesses were estimated by 22MHz non-invasive ultrasound in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, and about one year postpartum. A thick intima, thin media and high I/M ratio indicate a less healthy artery wall.RESULTS: During pregnancy serum PTX3 correlated positively with intima thickness and I/M ratio but negatively with media thickness (all p<0.0001), indicating adverse arterial effects. About one year postpartum, PTX3 levels had decreased in both groups and there remained no significant group difference or significant correlation with CCA wall layers.CONCLUSIONS: Higher levels of serum PTX3 in women with PE were significantly associated with signs of adverse arterial effects during pregnancy, but not one year postpartum, supporting the rapid dynamics of PTX3.
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9.
  • Akhter, Tansim, 1967-, et al. (author)
  • Sub-clinical atherosclerosis in the common carotid artery in women with/without previous pre-eclampsia : A seven-year follow-up
  • 2019
  • In: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 290, s. 206-213
  • Journal article (peer-reviewed)abstract
    • BACKGROUND AND AIMS: Pre-eclampsia is associated with increased risk of cardiovascular disease and premature death. However, conventional common carotid artery intima-media thickness (CCA-IMT) measurement does not reflect this. In contrast, measurement of the individual CCA intima and media thicknesses clearly indicates increased vascular risk both at diagnosis and about one year after pre-eclampsia. This study examined whether individual CCA wall layers, risk factors for cardiovascular disease, and markers of endothelial dysfunction had normalized or remained unfavorable seven years after pre-eclampsia.METHODS: The individual CCA intima and media thicknesses were measured using 22 MHz ultrasound. Conventional cardiovascular risk factors were recorded. A thick intima, thin media and high intima/media thickness ratio (I/M) are signs of sub-clinical atherosclerosis.RESULTS: The median age of women with previous pre-eclampsia (cases = 23) or normal pregnancies (controls = 35) was 39/37 years. At follow-up (median about seven years), the intima remained thicker and the I/M was higher in cases than in controls [all p < 0.0001; p < 0.001 after adjustment for time to follow-up, body mass index (BMI), and mean arterial pressure (MAP)], whereas the CCA-IMT was illogically thinner. Further, BMI, MAP, hip circumference, abdominal height, serum endostatin and apolipoprotein B levels were higher in cases (all p < 0.05). Intima and I/M measurements were correlated with age, MAP, endostatin and apolipoprotein B, whereas no logical correlations were found for CCA-IMT.CONCLUSIONS: The arteries in cases but not controls were still adversely affected after seven years. Measuring intima thickness and I/M appears preferable to measuring CCA-IMT for demonstrating vascular risk after pre-eclampsia.
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10.
  • Akhter, Tansim, 1967-, et al. (author)
  • Thicknesses of individual layers of artery wall indicate increased cardiovascular risk in severe pre-eclampsia
  • 2014
  • In: Ultrasound in Obstetrics and Gynecology. - : John Wiley & Sons. - 0960-7692 .- 1469-0705. ; 43:6, s. 675-680
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Pre-eclampsia, especially severe pre-eclampsia, is associated with an increased risk of cardiovascular disease later in life. However, ultrasound assessments of the common carotid artery intima-media thickness (CCA-IMT) do not convincingly demonstrate this. The aim of this study was to assess whether the individual thickness of the CCA intima and media layers and calculation of intima/media ratio (I/M) indicate an increased cardiovascular risk in women with previous severe pre-eclampsia.METHODS: The thicknesses of the CCA intima and media layers were obtained by non-invasive high-frequency ultrasound (22 MHz) in 42 women with previous severe pre-eclampsia and 44 women with previous normal pregnancies. A thick intima, thin media and high I/M are signs of a less healthy artery wall.RESULTS: Women with previous severe pre-eclampsia had a thicker CCA intima and a higher I/M than women with previous normal pregnancies, also after adjustment for mean arterial pressure, body mass index and CCA-IMT (all p < 0.0001). CCA-IMT did not differ significantly between the groups. In receiver operating characteristic curve analysis, intima thickness and I/M clearly discriminated between women with and without previous pre-eclampsia (c value about 0.95), whereas CCA-IMT did not (c = 0.52).CONCLUSIONS: Estimation of the individual CCA intima and media layers using high-frequency ultrasound and calculation of the I/M clearly demonstrated the well known increased cardiovascular risk in women with pre-eclampsia, whereas CCA-IMT did not. This method appears preferable to measuring CCA-IMT for imaging arterial effects and the increased cardiovascular risk in women with previous severe pre-eclampsia.
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11.
  • Al-Saqi, Shahla Hamza, et al. (author)
  • Oxytocin improves cytological and histological profiles of vaginal atrophy in postmenopausal women
  • 2016
  • In: Post Reproductive Health. - : SAGE Publications. - 2053-3691 .- 2053-3705. ; 22:1, s. 25-33
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To investigate if topical oxytocin can reverse vaginal atrophy, as assessed by cytological and histological examination of the vaginal mucosal epithelium, in postmenopausal women after 12 weeks of treatment as compared to placebo.STUDY DESIGN: Sixty-eight postmenopausal women diagnosed with vaginal atrophy were randomized for this multicenter, double-blinded, placebo-controlled trial. Thirty-three women received 600 IU vagitocin, an oxytocin containing gel, and 35 women received a placebo gel intravaginally. The dose was 600 IU daily for the first two weeks and thereafter 600 IU twice a week for 10 weeks. All participant women underwent four visits and a subgroup of 20 women had a further fifth visit. Vaginal smears for cytological evaluation were collected at all visits. Vaginal biopsies were taken in 20 women before and after 12 weeks of treatment for histological analysis. In these women a vaginal smear was also collected after 14 weeks.RESULTS: The increase in the percentage of superficial cells between 0 and 2 weeks was significantly greater after treatment with vagitocin in comparison with placebo (p = 0.04). The difference in the maturation value between 0 and 12 weeks was significantly higher in the vagitocin than in the placebo group (p = 0.01). The reduction in the scores of atrophy was according to the histological investigation significantly greater in the vagitocin group than in the placebo group at 12 weeks (p < 0.04).CONCLUSION: Daily intravaginal treatment with vagitocin 600 IU improves expressions of vaginal atrophy as recorded by cytological investigation of vaginal smears and histological analysis of vaginal biopsies. Treatment twice weekly seems to be less effective regarding the increase in superficial cells.
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12.
  • Bergman, Lina, et al. (author)
  • Cerebral Biomarkers in Women With Preeclampsia Are Still Elevated 1 Year Postpartum
  • 2016
  • In: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 29:12, s. 1374-1379
  • Journal article (peer-reviewed)abstract
    • BACKGROUND There is evidence of cerebral involvement among women with preeclampsia. Levels of the cerebral biomarkers neuron-specific enolase (NSE) and S100B are elevated during pregnancy in women developing preeclampsia. It is although not known if these biomarkers return to normal range postpartum. The aim with this study was to compare levels of S100B and NSE during pregnancy and 1 year postpartum in women who have had preeclampsia to women with normal pregnancies. METHODS This study was a longitudinal study of cases (n = 53) with preeclampsia and controls (n = 58) consisted of normal pregnant women in matched gestational weeks. Plasma samples were collected at inclusion during pregnancy and 1 year postpartum. Plasma samples were analyzed for levels of S100B and NSE by enzyme-linked immunosorbent assays kits. RESULTS Levels of NSE and S100B in women with preeclampsia were higher during pregnancy than in women with normal pregnancies. One year postpartum, women who have had preeclampsia still had a higher median level of both NSE (5.07 vs. 4.28 mu g/l, P < 0.05) and S100B (0.07 vs. 0.06 mu g/l, P < 0.05) compared to women with previous normal pregnancies. High levels of NSE and S100B postpartum remained associated with previous preeclampsia after adjustment for confounding factors. Levels of NSE correlated to S100B during pregnancy and postpartum. CONCLUSIONS Levels of NSE and S100B are still elevated 1 year postpartum in women who have had preeclampsia in contrast to women with previous normal pregnancies. We hypothesize that there might be a persistent cerebral involvement among women with preeclampsia even 1 year postpartum.
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  • Bergman, Lina, et al. (author)
  • Plasma Levels of S100B in Preeclampsia and Association With Possible Central Nervous System Effects
  • 2014
  • In: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 27:8, s. 1105-1111
  • Journal article (peer-reviewed)abstract
    • BACKGROUND:S100B is supposed to be a peripheral biomarker of central nervous system (CNS) injury. The purpose of this study was to compare levels of S100B in women with preeclampsia with levels in healthy pregnant control subjects and furthermore to analyze levels of S100B in relation to possible CNS effects.METHODS:A cross-sectional case-control study in antenatal care centers in Uppsala, Sweden, was performed. Fifty-three women with preeclampsia and 58 healthy pregnant women were recruited at similar gestational length; women with preeclampsia were recruited at time of diagnosis, and control subjects were recruited during their routine visit to an antenatal clinic. Plasma samples were collected, and levels of S100B were analyzed with an enzyme-linked immunosorbent assay. Information about demographic and clinical characteristics, including symptoms related to CNS affection, was collected from the medical records. The main outcome measures were plasma levels of S100B and possible CNS effects.RESULTS:Levels of S100B were significantly higher among women with preeclampsia than among control subjects (0.12 µg/L vs. 0.07 µg/L; P < 0.001). In preeclampsia, there was a significant association between high levels of S100B and visual disturbances (P < 0.05).CONCLUSIONS:S100B is increased among women with preeclampsia, and high levels of S100B associate with visual disturbances, which might reflect CNS affection in women with preeclampsia.
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  • Bohman, Hannes, 1965-, et al. (author)
  • Preclinical atherosclerosis in adolescents with psychotic or bipolar disorders investigated with carotid high-frequency ultrasound.
  • 2020
  • In: Brain and Behavior. - : Wiley. - 2162-3279 .- 2162-3279. ; 10:12
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Early-onset psychosis (EOP) and bipolar disorder (EOBP) (at <18 years of age), are associated with an increased future risk of cardiovascular disease (CVD) and premature death. Yet it is unknown whether the arteries show visible signs of atherosclerosis in EOP and EOBP. This study investigated whether having EOP or EOBP was associated with detectable signs of preclinical atherosclerosis.METHOD: By using 22 MHz high-frequency ultrasound, different layers of the arterial wall of the left common carotid artery (LCCA) were assessed in 77 individuals with EOP (n = 25), EOBP (n = 22), and in age-matched healthy controls (n = 30). Conventional CVD confounders were included in the analyses.RESULTS: Adolescents with EOP and EOBP, compared to controls, had a significantly thicker LCCA intima thickness (0.132 vs. 0.095 mm, p < .001) and intima/media ratio (0.24 vs. 0.17 p < .001). There was a nonsignificant intima difference between EOP and EOBP. Conventional CVD risk factors did not explain the association between EOP/EOBP and intima thickness. In the group of EOP/EOBP, there was a significant correlation between the dose of current antipsychotic medication and intima thickness; however, the correlation was attenuated to a nonsignificant level when adjusted for global function.CONCLUSIONS: Adolescents with EOP or EOBP had an increased LCCA intima thickness, interpreted as a sign of preclinical atherosclerosis. Global function of the disorders was the strongest determinant of intima thickness. The findings, if replicated, might have implications for long-term treatment of EOP and EOBP in order to reduce a future risk of CVD.
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  • Bohman, Hannes, 1965-, et al. (author)
  • Thicker carotid intima layer, thinner media layer and higher intima/media ratio in women with recurrent depressive disorders : a pilot study using non-invasive high frequency ultrasound
  • 2010
  • In: World Journal of Biological Psychiatry. - : Informa Healthcare. - 1562-2975 .- 1814-1412. ; 11:1, s. 71-75
  • Journal article (peer-reviewed)abstract
    • Background. Growing evidence indicates that depression is an important risk factor for coronary heart disease. Thus, the aim of the present study has been to investigate if young women with adolescent onset and recurrent depressive disorders have signs of carotid intima and media changes already at the age of 30. Methods. Fifteen subjects with adolescent onset recurrent depressive disorders, mean age 31.5 years, were compared to 20 healthy women with a mean age of 39.6 years. The thickness of carotid artery intima and media was assessed, using non-invasive high-frequency ultrasound (25MHz). Results. The subjects with recurrent depressive disorders had significantly thicker carotid intima, significantly thinner carotid media and significantly higher intima/media ratio despite the fact that they were about 10 years younger than the healthy women. Hypertension, obesity or smoking could not explain the results. Conclusion. Already at the age of 30, subjects with recurrent depressive disorders with adolescent onset do have early signs of carotid intima and media changes, indicating a less healthy artery wall, despite otherwise no clinical signs of cardiovascular disease.
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17.
  • Damberg, Mattias, et al. (author)
  • Investigation of transcription factor AP-2 beta genotype in women with premenstrual dysphoric disorder.
  • 2005
  • In: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 377:1, s. 49-52
  • Journal article (peer-reviewed)abstract
    • It has repeatedly been shown that the serotonergic system is involved in the symptomatology of premenstrual dysphoric disorder (PMDD). Women with PMDD are reported to differ from symptom-free controls with regard to serotonin-related biological markers. Evidence from family and twin studies suggests a genetic contribution to the aetiology of PMDD. The expression of human transcription factor AP-2beta in neural crest cell lineages and neuroectodermal cells suggests that this protein may be of importance for functional characteristics of neurons by regulating the expression of target genes. Within the monoaminergic systems, several genes have binding sites for AP-2beta in regulatory regions, suggesting an involvement of AP-2beta in these systems. The gene encoding AP-2beta is located on chromosome 6p12-p21.1 and includes a polymorphic region consisting of a variable number of [CAAA] repeats located in the second intron. We have earlier shown that AP-2beta genotype is associated with serotonergic phenotypes and that brainstem levels of AP-2beta correlate positively to serotonin metabolism in rat frontal cortex. The aim of this study was to investigate the relationship between PMDD and transcription factor AP-2beta genotype. The participants included 176 women with PMDD and 91 healthy controls. Genotyping was performed by polymerase chain reactions. We did not observe any differences in AP-2beta genotype frequencies between PMDD subjects and controls. Our results suggest that AP-2beta genotype is not a risk factor for PMDD. To our knowledge, this is the first study investigating transcription factor AP-2beta genotype in women with PMDD. Hence, these results should be considered preliminary until replicated.
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  • Darj, Elisabeth, et al. (author)
  • Ultrasonographic blood flow measurement in the carotid arteries in postmenopausal women
  • 1999
  • In: Gynecologic and Obstetric Investigation. - : S. Karger AG. - 0378-7346 .- 1423-002X. ; 47:1, s. 20-25
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: The aim of the present study was to evaluate blood flow in postmenopausal women on hormone replacement therapy (HRT) compared to controls. Blood flow was ultrasonographically measured in the great arteries of the neck instead of in the vessels of the internal genital organs. METHODS: Fifty healthy women with climacteric complaints, at least 6 months postmenopausal, participated in the study. They were randomly divided into two groups. One group received 2 mg estradiol (E2) for 12 days, continued with 2 mg E2 and 1 mg norethisterone acetate for 10 days, followed by 1 mg E2 for 6 days, cyclically during 6 months. The other group received placebo tablets the first 3 months and the same HRT as the first group for the last 3 months. Blood flow was measured ultrasonographically by color flow pulsed Doppler in the common (CCA), internal (ICA) and external (ECA) carotid arteries, before the start of the study, after 3 and 6 months of therapy. RESULTS: CCA and ICA, both low resistance vessels, and ECA, a high resistance vessel, and their waveforms were identified. Pulsatility index did not decrease statistically significant (p > 0.05) in any of the great vessels during 6 months of HRT in this study. There were no differences in blood flow between the HRT-treated group compared to control group during 3 months of therapy, except for the right ECA (p = 0.04). CONCLUSION: The difference in blood flow and wave-forms of the major arteries of the neck were clearly shown, but HRT did not have any important impact on the blood flow in this study. No difference was shown concerning blood flow between the two groups of postmenopausal women, on active therapy or placebo.
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21.
  • Eriksson, Olle, et al. (author)
  • Mood changes correlate to changes in brain serotonin precursor trapping in women with premenstrual dysphoria.
  • 2006
  • In: Psychiatry research. - : Elsevier BV. - 0165-1781 .- 0925-4927 .- 1872-7506. ; 146:2, s. 107-16
  • Journal article (peer-reviewed)abstract
    • The cardinal mood symptoms of premenstrual dysphoria can be effectively treated by serotonin-augmenting drugs. The aim of the study was to test the serotonin hypothesis of this disorder, i.e. of an association between premenstrual decline in brain serotonin function and concomitant worsening of self-rated cardinal mood symptoms. Positron emission tomography was used to assess changes in brain trapping of 11C-labeled 5-hydroxytryptophan, the immediate precursor of serotonin, in the follicular and premenstrual phases of the menstrual cycle in eight women with premenstrual dysphoria. Changes in mood and physical symptoms were assessed from daily visual analog scale ratings. Worsening of cardinal mood symptoms showed significant inverse associations with changes in brain serotonin precursor trapping; for the symptom "irritable", r(s)=-0.83, and for "depressed mood" r(s)=-0.81. Positive mood variables showed positive associations, whereas physical symptoms generally displayed weak or no associations. The data indicate strong inverse associations between worsening of cardinal symptoms of premenstrual dysphoria and brain serotonin precursor (11C-labeled 5-hydroxytryptophan) trapping. The results may in part support a role for serotonin in premenstrual dysphoria and may provide a clue to the effectiveness of serotonin-augmenting drugs in this disorder but should, due to small sample size and methodological shortcomings, be considered preliminary.
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22.
  • Eriksson, Olle, 1954-, et al. (author)
  • Ovarian morphology in premenstrual dysphoria
  • 2012
  • In: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 37:6, s. 742-751
  • Journal article (peer-reviewed)abstract
    • Ovarian cyclicity is a prerequisite for premenstrual dysphoria (PMD), as illustrated by the fact that this condition is effectively eliminated by ovariectomy or by treatment with a GnRH agonist. Despite the possibility of differences in ovarian function between women with and without PMD, no study comparing ovarian morphology in these two groups has ever been published. Fifty-two women were recruited for this study; 26 had premenstrual dysphoria, fulfilling criteria slightly modified from those of the premenstrual dysphoric disorder, and 26 were asymptomatic age-matched controls. Ovarian morphology was assessed using transvaginal 7MHz ultrasonography on day 5 after the start of menses, and venous blood was sampled for hormone analysis on days 3 and 8, the expected day of ovulation, and day -4 of the menstrual cycle. There were no significant differences between the groups with respect to the prevalence of polycystic ovaries (PCO), the total number of follicles, the total ovarian volume or serum levels of androgen hormones. In addition, serum free testosterone levels in late premenstrual phase showed an inverse association to premenstrual symptoms of irritability and a similar inverse association trend to symptoms of depressed mood. Unexpectedly, the prevalence of ovaries with fewer than five antral or growing follicles was significantly higher in women with PMD than in controls (p=0.016). While the results do not support a role for PCO or androgen hormones in eliciting late luteal phase irritability, the possible relationship between oligofollicular ovaries and PMD deserves further study.
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23.
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24.
  • Eriksson, Olle, 1954- (author)
  • Studies on Premenstrual Dysphoria
  • 2005
  • Doctoral thesis (other academic/artistic)abstract
    • Premenstrual dysphoria, so severe that it affects the lives of the women afflicted, is the condition studied in this thesis. Physiological and pharmacological mechanisms of pathogenetic relevance were investigated. Women with premenstrual dysphoria showed a stronger and less dampened response of LH to an estradiol challenge than asymptomatic women, indicating an altered neuroendocrine regulation. In women with premenstrual dysphoria, the LH response was correlated to the severity of irritability and bloating, and the early FSH response was correlated to the severity of depressed mood. The positron-emission study showed strong, consistent correlations between worsening of mood symptoms and a decrease in brain trapping of the immediate serotonin precursor, from the mid-follicular to the late luteal phase in women with premenstrual dysphoria. The strongest correlations were seen for the cardinal mood symptoms of premenstrual dysphoria, and for their opposites. Physical symptoms showed weaker or no correlations with the exception of nociceptive symptoms from erogenous body regions which showed positive correlations to serotonin precursor trapping in the right caudate nucleus. The findings are consistent with the serotonin hypothesis of premenstrual dysphoria, and might possibly explain the observed effects of serotonin-augmenting drugs in this condition.The partial 5-HT1A receptor agonist buspirone was superior to placebo in the treatment of premenstrual dysphoria. The weak SRI and 5-HT2 receptor antagonist nefazodone was not superior to placebo. For women with premenstrual dysphoria in need of medication and who do not tolerate SRIs because of the sexual sideeffects, buspirone may be an alternative drug, since it had no adverse effects on sexual function. The prevalence of polycystic ovaries and serum levels of androgens were not higher in women with premenstrual dysphoria than in their asymptomatic counterparts. The findings are not consistent with the hypothesis that irritability in women with premenstrual dysphoria is induced by elevated testosterone levels. Thesis results, which are in line with the serotonin hypothesis of premenstrual dysphoria, may imply that increased brain sensitivity is one of the factors underlying severe premenstrual mood symptoms, thereby further supporting a common serotonergic dysregulation in this condition.
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25.
  • Eriksson, Olle, 1954-, et al. (author)
  • Women with Premenstrual Dysphoria Lack the Seemingly Normal Premenstrual Right-Sided Relative Dominance of 5-HTP-Derived Serotonergic Activity in the Dorsolateral Prefrontal Cortices - A Possible Cause of Disabling Mood Symptoms.
  • 2016
  • In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 11:9
  • Journal article (peer-reviewed)abstract
    • To investigate potential quantitative and qualitative differences in brain serotonergic activity between women with Premenstrual Dysphoria (PMD) and asymptomatic controls.Serotonin-augmenting drugs alleviate premenstrual mood symptoms in the majority of women with PMD while serotonin-depleting diets worsen PMD symptoms, both indicating intrinsic differences in brain serotonergic activity in women with PMD compared to asymptomatic women.Positron-emission tomography with the immediate precursor of serotonin, 5-hydroxytryptophan (5-HTP), radiolabelled by 11C in the beta-3 position, was performed in the follicular and luteal phases for 12 women with PMD and 8 control women. Brain radioactivity-a proxy for serotonin precursor uptake and synthesis-was measured in 9 regions of interest (ROIs): the right and left sides of the medial prefrontal cortex, dorsolateral prefrontal cortex, putamen and caudate nucleus, and the single "whole brain".There were no significant quantitative differences in brain 5-HTP-derived activity between the groups in either of the menstrual phases for any of the 9 ROIs. However, multivariate analysis revealed a significant quantitative and qualitative difference between the groups. Asymptomatic control women showed a premenstrual right sided relative increase in dorsolateral prefrontal cortex 5-HTP derived activity, whereas PMD women displayed the opposite (p = 0.0001). Menstrual phase changes in this asymmetry (premenstrual-follicular) correlated with changes in self ratings of 'irritability' for the entire group (rs = -0.595, p = 0.006). The PMD group showed a strong inverse correlation between phase changes (premenstrual-follicular) in plasma levels of estradiol and phase changes in the laterality (dx/sin) of radiotracer activity in the dorsolateral prefrontal ROI (rs = -0.635; 0.027). The control group showed no such correlation.Absence of increased premenstrual right-sided relative 5-HTP-derived activity of the dorsolateral prefrontal cortices was found to strongly correlate to premenstrual irritability. A causal relationship here seems plausible, and the findings give further support to an underlying frontal brain disturbance in hormonally influenced serotonergic activity in women with PMD. Because of the small number of subjects in the study, these results should be considered preliminary, requiring verification in larger studies.
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26.
  • Frisk, Per, et al. (author)
  • Risk factors for cardiovascular disease are increased in young adults treated with stem cell transplantation during childhood
  • 2012
  • In: Pediatric Transplantation. - : Wiley. - 1397-3142 .- 1399-3046. ; 16:4, s. 385-391
  • Journal article (peer-reviewed)abstract
    • We measured risk factors for CVD in 18 patients at a median of 18.2 yr after SCT and in sex and age-matched controls. Three patients (17%), but none of the controls, met the criteria for the MetS (p = 0.25). In the patients, we found higher levels of triglycerides (0.94 vs. 0.62 mm, p = 0.019), total cholesterol (5.1 vs. 4.0 mm, p = 0.017), LDL (3.4 vs. 2.6 mm, p = 0.019), apolipoprotein B (1.04 vs. 0.74 g/L, p = 0.004), apolipoprotein B/A1 ratio (0.7 vs. 0.5, p = 0.026), and lower levels of adiponectin (4.9 vs. 7.5 mg/L, p = 0.008) than in the controls. The patients had a lower GHmax (9 vs. 20.7 mU/L, p = 0.002). GHmax was significantly correlated inversely with triglycerides (r = -0.64, p = 0.008), total cholesterol (r = -0.61, p = 0.011), apolipoprotein B (r = -0.60, p = 0.014), and apolipoprotein B/A1 ratio (r = -0.66, p = 0.005). We recorded a significantly thicker carotid intima layer among the patients than among matched controls (0.15 vs. 0.13 mm, p = 0.034). The level of adiponectin correlated inversely with carotid intima thickness (r = -0.55, p = 0.023). After SCT in childhood, long-term survivors may be at risk of developing premature CVD.
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27.
  • Hallberg, Gunilla (author)
  • Effects of Endogenous and Exogenous Hormones on the Female Breast : With Special Reference to the Expression of Proteoglycans
  • 2011
  • Doctoral thesis (other academic/artistic)abstract
    • This thesis aims to study the effects of endogenous and exogenous hormones and mammographic breast density (BD) on cellular markers in non-cancerous female breast tissue. Women on the waiting list for breast reduction plastic surgery were recruited (n = 79), and randomized to 2 months of hormone therapy or no therapy before surgery. The women had a mammogram and a needle biopsy 2 months before surgery and tissue samples were obtained at the operation. In premenopausal women, estrogen receptor (ER)α levels were associated with age (p = 0.0002), were similar in the follicular and luteal phases of the menstrual cycle and were higher in parous than in nulliparous women (p = 0.009). Current smokers had lower PR levels than non-smokers (p = 0.019). Women on oral contraception had lower ERα (p = 0.048) and PR (p = 0.007) levels than women in the follicular phase. The ERα levels did not differ significantly between postmenopausal estrogen and estrogen-progestogen users, but PR levels were lower among estrogen-progestogen users (p = 0.03). We found lower expression of the genes for decorin and syndecans 1 and 4 in the luteal phase than in the follicular phase, among parous women. Protein levels of the androgen receptor, syndecan-4 and decorin was lower in premenopausal women who were using oral contraceptives (OC) than in those in the follicular phase (p = 0.002 - 0.02), whereas no significant differences between OC use and the luteal phase were found. In premenopausal women, BD was negatively associated with age and body mass index but was similar for the menstrual phases. Breast density was associated with genetic expression of the androgen receptor and remained significant after adjustment for age (rs = 0.56; p = 0.04). After adjustement for age, breast density was also marginally associated with expression of the caspase 3 gene (0.55; 0.053). However, protein levels of caspase 3 was negatively associated (-0.61; 0.03).
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28.
  • Hallberg, Gunilla, et al. (author)
  • Effects of pre-and postmenopausal use of exogenous hormones on receptor content in normal human breast tissue: A randomized study
  • 2008
  • In: Gynecological Endocrinology. - : Informa UK Limited. - 0951-3590 .- 1473-0766. ; 24:8, s. 475-480
  • Journal article (peer-reviewed)abstract
    • Objective. To examine the effects of exposure to endogenous and exogenous hormones on estrogen receptor- (ER) and progesterone receptor (PR) levels in normal human breast tissue. Methods. In a randomized study of women scheduled for mammary reduction plasty (n = 81), ER and PR content in breast parenchyma was analyzed in premenopausal (n = 49) and postmenopausal (n = 16) women. Premenopausal women were randomized to surgery in the follicular or luteal phase of the menstrual cycle or after oral contraceptive treatment for 2 months. Postmenopausal women were randomized to sequential or estrogen-only therapy for 2 months prior to surgery. Results. ER content was higher in parous than in nulliparous (p = 0.009) premenopausal women and displayed a positive association with age (rs = 0.51, p = 0.0002). Compared with premenopausal women in the follicular phase, postmenopausal women had higher ER content (p = 0.040) whereas premenopausal women on oral contraception had lower ER (p = 0.048) and PR (p = 0.007) content. Smokers had lower PR content than non-smokers (p = 0.02). Conclusion. In the present study ER content was higher in parous than in non-parous women and associated with premenopausal age. Short-term oral contraceptives yielded lower ER and PR contents. Postmenopausal estrogen/progestogen combined therapy yielded lower PR content than estrogen-only therapy.
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29.
  • Hallberg, Gunilla, et al. (author)
  • Mammographic breast density and the expression of androgen receptor, caspase 3, Ki67 and proteoglycans in pre-menopausal women.
  • Other publication (other academic/artistic)abstract
    • Abstract   Background: Mammographic breast density (BD) is a strong risk factor for breast cancer, but underlying histopathological correlates are not fully understood. In the human breast the main part of the volume constitutes of stroma. We examined the correlation between BD and Ki67, caspase 3, androgen receptor (AR), syndecan-1 , syndecan –4 and decorin in pre-menopausal non cancerous breast tissue. Method: Pre-menopausal women (n = 55), planned for a reduction mammoplasty and having a breast sample (needle biopsy) at the same time of preoperative mammography, were included. Protein levels of the proteoglycans syndecan-1, syndecan-4, decorin and the AR, Ki67 and caspase 3, were examined by immunohistochemistry (IHC) and gene expression by real-time RT-PCR. Results were compared with regard to BD class (< 20% vs. > 40%) and mean BD (%), using non-parametric analysis and adjustments.  Results: BD (%) decreased significantly with age (p < 0.0001) and with BMI (p = 0.002) but was similar in the follicular and luteal phases. The AR gene expression increased significantly with increasing BD class and with mean BD% (rs = 0.43; p = 0.048, for both), and was strengthened after adjustment for age. After adjustment for age, caspace 3 was positively associated with mean BD (%), with borderline significance (0.55; 0.053), whereas IHC was negatively associated to BD class (-0.61; 0.026). PCR values for Ki67, syndecan-1 and syndecan-4 were numerically higher in dense breasts (p > 0.05 for all). Conclusion: In pre-menopausal women, gene expression for AR and caspase 3 increased, whereas protein levels of caspase 3 might decrease, with increasing breast density. This limited study showed no significant associations between Ki67, syndecans, decorin and breast density.  
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30.
  • Hallberg, Gunilla, et al. (author)
  • The effect of short-term oral contraceptive use on the expression of syndecan-1, syndecan-4, decorin and the androgen receptor in breast tissue from women of fertile age
  • 2011
  • In: The Breast Journal. - 1075-122X .- 1524-4741.
  • Journal article (other academic/artistic)abstract
    • BackgroundIn non-cancerous breast tissue from premenopausal women, we examined gene expression and protein levels of the androgen receptor and the proteoglycans decorin, syndecan-1 and syndecan-4, before and after use of oral contraceptives (OC).Material and MethodsPremenopausal women (n = 20) undergoing breast reduction plastic surgery, received two months use of  combined oral contraceptive with ethinylestradiol 30μg and levonorgestrel 150μg. Breast tissue was sampled at mammography (needle biopsy) two months before and at the operation. We analysed immunohistochemistry (n = 20) and real-time RT-PCR (n = 10).ResultsAfter two months of OC use, we found a significant decrease in the protein levels of syndecan-4 (p = 0.003), the androgen receptor (p = 0.002) and decorin (p = 0.018), but not of syndecan-1 protein, compared to expression during the follicular phase in the normal menstrual cycle before OC use.  Real- time RT-PCR indicated a significant decrease in gene expression for decorin (p = 0.002).  ConclusionsIn pre-menopausal women, short-term OC use yielded lower protein levels of syndecan-4, the androgen receptor and decorin, and lower gene expression for decorin, compared to that during the follicular phase of the menstrual cycle before OC use.
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31.
  • Hallberg, Gunilla, et al. (author)
  • The expression of syndecan-1, syndecan-4 and decorin in healthy human breast tissue during the menstrual cycle
  • 2010
  • In: Reproductive Biology and Endocrinology. - : Springer Science and Business Media LLC. - 1477-7827. ; 8, s. 35-41
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: In order to unravel the interactions between the epithelium and the extra cellular matrix (ECM) in breast tissue progressing to cancer, it is necessary to understand the relevant interactions in healthy tissue under normal physiologic settings. Proteoglycans in the ECM play an important role in the signaling between the different tissue compartments. The proteoglycan decorin is abundant in the breast stroma. Decreased expression in breast cancer tissue is a sign of a poor tumor prognosis. The heparane sulphate proteoglycans syndecan-1 and syndecan-4 promote the integration of cellular adhesion and proliferation. The aim of this study was to investigate the gene expression and location of decorin, syndecan-1 and syndecan-4 in the healthy breast during the menstrual cycle. METHODS: Tissue from healthy women undergoing breast reduction plastic surgery was examined using immunohistochemistry (n = 38) and Real-Time RT-PCR (n = 20). Both parous and nulliparous women were eligible and the mean age of the women was 34(+/- 10 years) with regular menstrual cycles (28 +/- 7 days). None of the women had used hormonal treatment the last three months. The women were randomized to needle biopsy two months before the operation in the follicular or luteal menstrual phase and for another biopsy at the operation in the opposite phase. Serum samples were obtained to characterize the menstrual phase. The Wilcoxon signed rank test and Mann Whitney test were used for statistical analyses. RESULTS: By real time-RT-PCR the gene signal for all three proteoglycans; decorin (p = 0.02) and syndecan-1 (p = 0.03) and syndecan-4 (p = 0.02) was significantly lower among parous women in the luteal phase than in the follicular phase. Immunohistochemistry confirmed the identification of the proteins but no significant difference between menstrual phases was observed. Serum samples verified the menstrual phase. CONCLUSIONS: Our study shows, for the first time in the healthy breast, a significantly lower expression of the genes for the three proteoglycans, decorin, syndecan-1 and syndecan-4 in the luteal phase during the menstrual cycle. These changes were registered under normal physiologic conditions. Since ECM molecules appear to be involved in tumor progression, these findings in the normal breast could constitute a base for further studies in women receiving hormonal therapy or those with breast cancer.
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32.
  • Hanrieder, Jörg, 1980, et al. (author)
  • Proteomic analysis of human follicular fluid using an alternative bottom-up approach.
  • 2008
  • In: Journal of proteome research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 7:1, s. 443-9
  • Journal article (peer-reviewed)abstract
    • Human follicular fluid (hFF) is the in vivo environment of oocytes during follicular maturation in the ovaries. It contains a huge variety of compounds such as, e.g., proteins that might play an important role in follicular development and oocyte growth. Previous proteomic studies on follicular fluid have isolated and already identified a certain number of proteins. Nevertheless, only a small part of proteins present in follicular fluid have been covered so far and a large number have still not been identified. Therefore, the need for new, more resolving, and sensitive approaches in proteome research is evident. We utilized a proteomic setup based on in solution isoelectric focusing (IEF) and reversed-phase nanoliquid chromatography coupled to matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (nano-LC MALDI TOF/TOF MS) for in depth protein analysis of human follicular fluid samples of patients undergoing controlled ovarian hyper stimulation (COH) for in vitro fertilization therapy (IVF). This approach led to the significant identification of 69 proteins, where 32 have not been reported before to be found in human follicular fluid with proteomic methods. Among these findings, at least two relevant compounds essentially involved in hormone secretion regulation during the folliculogenetic process were identified: sex hormone binding globulin (SHBG) and inhibin A (INHA). To confirm these results, both proteins were further validated by immunoassays.
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33.
  • Johnsson, Inger W, 1973-, et al. (author)
  • High birth weight was associated with increased radial artery intima thickness but not with other investigated cardiovascular risk factors in adulthood
  • 2018
  • In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 12, s. 2152-2157
  • Journal article (peer-reviewed)abstract
    • AIM: This study investigated whether a high birth weight was associated with increased risk factors for cardiovascular disease when Swedish adults reached 34-40.METHODS: We studied 27 subjects born at Uppsala University Hospital in 1975-1979, weighing at least 4500 g, and compared them with 27 controls selected by the Swedish National Board of Welfare with birth weights within ±1 standard deviations scores and similar ages and gender. The study included body mass index (BMI), blood pressure, lipid profile, haemoglobin A1c (HbA1c), C-reactive protein (CRP) and high-frequency ultrasound measurements of intima-media thickness, intima thickness (IT) and intima:media ratio of the carotid and radial arteries.RESULTS: Subjects with a high birth weight did not differ from controls with regard to BMI, blood pressure, lipid profile, high-sensitivity CRP, HbA1c or carotid artery wall dimensions. However, their radial artery intima thickness was 37% greater than the control group and their intima:media ratio was 44% higher.CONCLUSION: Our findings indicate that a high birth weight was associated with increased radial artery intima thickness, but not with other investigated cardiovascular risk factors, at 34-40 years of age. The clinical implications of these findings should be investigated further, especially in subjects born with a very high birth weight.
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34.
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35.
  • Kirilovas, Dmitrijus, et al. (author)
  • Conversion of circulating estrone sulfate to 17β-estradiol by ovarian tumor tissue : A possible mechanism behind elevated circulating concentrations of 17β-estradiol in postmenopausal women with ovarian tumors
  • 2007
  • In: Gynecological Endocrinology. - : Informa UK Limited. - 0951-3590 .- 1473-0766. ; 23:1, s. 25-28
  • Journal article (peer-reviewed)abstract
    • AIM: Elevated serum levels of 17beta-estradiol (E2) are frequently found in postmenopausal women with ovarian tumors not classified as estrogen-producing. Conversion of circulating estrone sulfate (E1S) to E2 is one alternative way of E2 formation in target tissues in postmenopausal women. Our aim was to find out if conversion of circulating E1S to E2 by the tumor tissue could be a reason for elevated serum E2 levels in postmenopausal women with 'non-estrogen-producing' ovarian tumors. METHOD: Serum E2 was measured in 12 postmenopausal women with 'non-estrogen-producing' ovarian tumors (nine benign, three malignant). Total hydrolysis of and [3H]E2 formation from [3H]E1S by the tumor tissue homogenates was studied in vitro. RESULTS: Serum E2 showed significant positive correlations with total hydrolysis of and [3H]E2 formation from [3H]E1S in the total material as well as in the benign tumor subgroup. [3H]E2 formation was the most important independent variable. CONCLUSION: Conversion of circulating E1S to E2 by the tumor tissue could be one important reason for elevated S-E2 levels in postmenopausal women with 'non-estrogen-producing' ovarian tumors.
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36.
  • Kirilovas, Dmitrijus, et al. (author)
  • Granulosa cell aromatase enzyme activity : Effects of follicular fluid from patients with polycystic ovary syndrome, using aromatase conversion and [11C]vorozole-binding assays
  • 2006
  • In: Gynecological Endocrinology. - : Informa UK Limited. - 0951-3590 .- 1473-0766. ; 22:12, s. 685-691
  • Journal article (peer-reviewed)abstract
    • The local regulation of ovarian aromatase enzyme in polycystic ovary syndrome (PCOS) was studied with aromatase conversion and [C-11]vorozole-binding assays to analyze aromatase activity, substrate-enzyme affinity and number of aromatase binding sites in non-cultured human granulosa cells (GC) incubated with different sources and preparations of follicular fluid (FF). Incubation with FF from women stimulated in in vitro fertilization cycles with follicle-stimulating hormone yielded higher conversion activity than with FF from healthy women and PCOS patients, paralleled with higher substrate affinity (lower K-d) than with FF from healthy women. In PCOS women, charcoal-pretreated FF yielded higher conversion, whereas the ether-pretreated FF yielded lower conversion activity, than with untreated PCOS FF. Both preparations of FF yielded higher affinity to substrate (lower Kd values) and the ether-pretreated FF a lower number of binding sites (B-max). It seems that steroids with the presence of proteins in PCOS FF reduced aromatase conversion activity through decreased substrate affinity, whereas FF preparations devoid of proteins reduced the aromatase conversion activity mainly through blocking of aromatase active sites. Identification of specific agents responsible for this rapid regulation of aromatase function might help to understand normal regulation of the menstrual cycle and supposed imbalances of inhibitors/activators in PCOS.
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37.
  • Kristjánsdóttir, Jóna, et al. (author)
  • Could SF-36 be used as a screening instrument for depression in a Swedish youth population?
  • 2011
  • In: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 25:2, s. 262-268
  • Journal article (peer-reviewed)abstract
    •  Objective: Depression among youth is a condition associated with serious long-term morbidity and suicide. The aim of this study was to investigate whether a HRQoL instrument, the short form 36 version 1.0 (SF-36), could be used to screen for depression in a clinical Youth Centre (YC). A second purpose was to describe self-reported health and depression. Setting: A clinical YC at a University hospital. Design: A sample of 660 youths, 14-20 years old was assessed with SF-36 and Montgomery Asberg Depression Rating Scale, self-screening version (MADRS-S). Answers to all the questions in both instruments were given by 79% (519/660; 453 women and 66 men). Mean age in the sample was 17.5 +/- 1.6 years. Results: Strong correlations were found between all the SF-36 subscales and the depression ratio scale MADRS-S. Receiver operating characteristic (ROC) curve analysis confirmed that the SF-36 subscales mental health (MH) and vitality (VT) could correctly predict depression on the individual level with Area Under the ROC Curve values 0.87 and 0.84 in ROC curves. Individuals scoring 48 or lower on MH and 40 or lower on VT should be followed up with a clinical interview concerning possible depressive disorder. Mild to moderate depression was common (35.5%), especially among women (37.5%). Men scored higher than women on all SF-36 subscales except for physical functioning. Conclusions: The SF-36 can be used to screen for suspect depression in a youth population followed by interview. This gives an opportunity to detect and treat emerging depressive symptoms early.
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38.
  • Kristjánsdóttir, Jóna, et al. (author)
  • Health-related quality of life in young women starting hormonal contraception : a pilot study
  • 2018
  • In: European journal of contraception & reproductive health care. - : TAYLOR & FRANCIS LTD. - 1362-5187 .- 1473-0782. ; 23:3, s. 171-178
  • Journal article (peer-reviewed)abstract
    • Objectives: Our purpose was to study whether there is a difference in self-rated health-related quality of life (HRQOL) and changes in HRQOL perception after 3 months of hormonal contraceptive use in adolescents. Seasonal variations in symptoms of depression were also studied. Methods: A test group (T1) (n=193) and a selected control group (n=238) of women aged 14-20 years who were visiting a young person's clinic completed the 36-item short-form health survey (SF-36) and answered additional questions on menstrual history and pattern, need for menstrual pain relief medication, and other regular medication. The test group was reassessed after 3 months of hormonal contraception (T2). Seasonal variations in reported SF-36 scores were studied for the whole group. Results: The selected control group and test group at T1 were similar with regard to age at menarche and menstrual pattern. The duration of bleeding and use of painkillers were significantly reduced and the impact on everyday life was significantly improved after 3 months of hormonal contraception (p=.000, two-tailed). No changes in HRQOL or symptoms of possible depression were found after 3 months of hormonal contraception. The highest prevalence odds ratio for possible depression (SF-36 mental health scale score <= 48), adjusted for group, season and age, for spring vs winter, was 2.15 (95% confidence interval 0.95, 4.85). Conclusions: After 3 months of hormonal contraception both the number of days of menstrual bleeding and the use of medication to relieve menstrual pain were reduced, but there were no significant changes in self-rated HRQOL perception. Seasonal effects on HRQOL were reported.
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39.
  • Kristjánsdóttir, Jóna, et al. (author)
  • Health-related self-assessed quality of life in young people at a Youth Centre in Sweden
  • 2009
  • In: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 23:3, s. 465-472
  • Journal article (peer-reviewed)abstract
    • Objective: To study the self-reported health of young people visiting a Youth Centre (YC) at a University hospital, describe possible gender differences and to compare the results with those in previous Swedish reports on similar age groups using the same instrument. Design: All young people who visited a YC at a particular, randomly chosen time, were verbally asked to fill out a questionnaire, Short Form 36. The interviews were conducted during a 12-month period to lessen the impact of seasonal variations. Setting: A YC at the department for obstetrics and gynaecology, Uppsala University hospital. Participants: A total of 1495 young people aged 14-25 years who visited the YC. Results: The study population (n = 1495). Response rate was 96%. This population reported lower overall scores compared with the normative Swedish population from 1992. Further, females scored significantly lower than males on all subscales (p < 0.001), except for 'Physical Functioning'. The lowest scores were reported for the subscales Vitality, Role Emotional and Mental Health. Conclusion: This study describes physical functioning and mental health among young people visiting a YC. The results indicate a worsening of the perceived physical and MH in young individuals, especially in young women. Further studies are needed to monitor changes in MH and quality of life over time in this group and assess the effects of interventions. This study enhances the importance of a holistic approach towards health and health promotion comprising both physical and mental health issues.
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40.
  • Kristjansdottir, Jona, et al. (author)
  • Self-reported health in adolescent girls varies according to the season and its relation to medication and hormonal contraception : A descriptive study
  • 2013
  • In: European journal of contraception & reproductive health care. - : Informa UK Limited. - 1362-5187 .- 1473-0782. ; 18:5, s. 343-354
  • Journal article (peer-reviewed)abstract
    • Objectives To study seasonal variations in self-rated health and depressive symptoms in adolescent girls and possible differences in reported health with regard to use of medications. Method The SF-36 questionnaire was completed by 1250 girls with a mean age of 17 years, who visited a health centre in the course of one year. From January to July inclusive, depressive symptoms in 453 of the participants were also assessed using MADRS-S. Age and regular medication data were recorded. Results Significantly better mental health and less depressive symptoms were reported during the summer, than in winter months. Seasonality was more related to the SF-36 mental, than physical health subscales. Respondents treated with hormonal contraceptives (HCs) only and those not taking any medication scored better on several SF-36 subscales, than girls on antidepressives and other medications. Respondents taking HCs tended to report better physical health and less depressive symptoms on MADRS-S than those taking no medication. Conclusions Adolescent girls showed seasonal variations in self-reported health and depressive symptoms, with more symptoms during winter months. HC users tended to report better physical health and less depressive symptoms than those on no medication. The high prevalence of suspected depression during the winter months deserves attention.
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41.
  • Kushnir, Mark M., et al. (author)
  • Exploratory study of the association of steroid profiles in stimulated ovarian follicular fluid with outcomes of IVF treatment
  • 2016
  • In: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 162, s. 126-133
  • Research review (peer-reviewed)abstract
    • Steroid concentrations in stimulated follicular fluid (sFF) samples have been linked to the quality of oocytes used in IVF treatments. Most of the published studies focused on evaluating the association of the IVF outcomes with only a few of the steroids, measured by immunoassays (IA). We performed a treatment outcome, prospective cohort study using stimulated FF sampled from 14 infertile women undergoing IVF treatment; single oocyte was used per IVF cycle. Fourteen endogenous steroids were analyzed in 22 ovarian follicle aspirations, which corresponded to the embryos used in the IVF. Ten oocytes were associated with live birth (LB) and 12 with no pregnancy (NP). Steroids were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Differences in distribution of concentrations in association with the pregnancy outcome (LB or NP), and receiver operating characteristic (ROC) curves analysis were performed for the entire cohort and for within-women data. The predominant androgen and estrogen in stimulated sFF were androstenedione (A4) and estradiol (E2), respectively. Lower concentrations of pregnenolone (Pr), lower ratios of A4/ dehydroepiandrosterone (DHEA), testosterone (Te)/DHEA, and greater ratios of E2/Te, and estrone/A4 were observed in sFF samples associated with LB. Among the oocytes associated with NP, in four out of 12 samples total concentration of androgens was above the distribution of the concentrations in the oocytes corresponding to the LB group. Observations of the study indicated increased consumption of precursors and increased biosynthesis of estrogens in the follicles associated with LB. Our data suggest that potentially steroid profiles in sFF obtained during oocyte retrieval may serve as biomarkers for selection of the best embryo to transfer after IVF.
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42.
  • Kushnir, Mark M., et al. (author)
  • Protein and Steroid Profiles in Follicular Fluid after Ovarian Hyperstimulation as Potential Biomarkers of IVF Outcome
  • 2012
  • In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 11:10, s. 5090-5100
  • Journal article (peer-reviewed)abstract
    • Controlled ovarian hyperstimulation is performed to assist with generation of multiple mature oocytes for use in in vitro fertilization (IVF). The goal of our study was to evaluate differences in protein and steroid profiles in ovarian follicular fluid (hFF) samples obtained during oocy-te retrieval from women undergoing IVF treatment and to identify physiological pathways associated with the proteins. The hFF samples were depleted of abundant proteins, fractionated by ultrafiltration, digested, and analyzed by nano-LC QTOF. Concentrations of 15 endogenous steroids were determined in the samples using LC-MS/MS methods. The total number of proteins identified in the samples was 75, of which 4, 7, and 2 were unique to the samples from women with viable pregnancy, miscarriage, and no pregnancy, respectively. Identified proteins were associated with the acute response signaling, coagulation system, intrinsic and extrinsic prothrombin activation, complement system, neuroprotective role of THOP1, FXR/RXR activation, role of tissue factor, and growth hormone pathways. A greater number of proteins associated with biosynthesis was found in hFF samples corresponding to the oocytes resulting in pregnancy. The abundance of seven proteins was found to be associated with steroidogenesis. The obtained data will contribute to better understanding of the pathogenesis and development of noninvasive markers for assessment of oocytes viability.
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43.
  • Kushnir, Mark M, et al. (author)
  • Steroid profiles in ovarian follicular fluid from regularly menstruating women and women after ovarian stimulation
  • 2009
  • In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 55:3, s. 519-526
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Information on the concentrations of steroids in ovarian follicular fluid (FF) from regularly menstruating (RM) women has been limited because of the absence of methods for the simultaneous quantification of multiple steroids in small volumes of FF. We studied steroid profiles in FF during the early follicular phase of the menstrual cycle and after ovarian stimulation for in vitro fertilization (IVF), and compared concentrations with published values obtained by immunoassay (IA). METHODS: We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure 13 steroids in 40-microL aliquots of FF samples from 21 RM women and from 5 women after ovarian stimulation for IVF. Relationships between concentrations of steroids and their ratios (representations of the enzyme activities) were evaluated within and between subgroups. RESULTS: The concentrations of testosterone (Te), androstenedione (A4), and estradiol (E2) measured by LC-MS/MS were lower than those previously reported in studies with IAs. In RM women, androgens were the most abundant class of steroids, with A4 being the major constituent. The concentrations of 17-hydroxyprogesterone (17OHP), total androgens, and estrogens were 200- to 1000-fold greater in FF than in serum. Compared with RM women, FF samples from women undergoing ovarian stimulation had significantly higher concentrations of E2 (P = 0.021), pregnenolone (P = 0.0022), 17OHP (P = 0.0007), and cortisol (F) (P = 0.0016), and significantly higher ratios of F to cortisone (P = 0.0006), E2 to estrone (P = 0.0008), and E2 to Te (P = 0.0013). CONCLUSIONS: The data provide the first MS-based concentration values for 13 steroids in ovarian FF from RM women, from estrogen- and androgen-dominant follicles, and from women after ovarian stimulation for IVF.
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44.
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45.
  • Leonard, Dag, et al. (author)
  • Increased carotid intima thickness and decreased media thickness in premenopausal women with systemic lupus erythematosus : an investigation by non-invasive high-frequency ultrasound
  • 2011
  • In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 40:4, s. 279-282
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE:To determine whether high-frequency ultrasound (US) yielding separate assessments of intima and media thickness gives additional information about the vascular morphology compared with the total common carotid artery intima-media thickness (CCA-IMT).METHODS:Using a 22 MHz US instrument, we determined the near-wall CCA-IMT, the intima and media layers, and the intima/media (I/M) ratio in 47 premenopausal women with systemic lupus erythematosus (SLE), 20 healthy women, and 17 postmenopausal women (mean ages 37, 40, and 69 years, respectively).RESULTS:In SLE, the carotid intima was thicker (0.19 ± 0.04 vs. 0.12 ± 0.02 mm), the media thinner (0.45 ± 0.12 vs. 0.68 ± 0.24 mm), the I/M ratio higher (0.45 ± 0.17 vs. 0.20 ± 0.07) (all p < 0.0001), and the CCA-IMT lower (0.64 ± 0.13 vs. 0.80 ± 0.25 mm, p < 0.01) compared to age-matched controls. The SLE patients had a thicker carotid intima compared to the postmenopausal women (0.19 ± 0.04 vs. 0.14 ± 0.03 mm, p < 0.0001) and a similar I/M ratio.CONCLUSION:Separate assessment of carotid artery wall layers demonstrated a thicker intima, thinner media, and a higher I/M ratio in women with SLE compared to healthy controls and indicated an artery wall status in SLE comparable to 30-years-older healthy women. Separate estimates of carotid intima and media layers may be preferable to CCA-IMT in SLE patients.
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46.
  • Ljunggren, Mirjam, et al. (author)
  • Obstructive sleep apnea during rapid eye movement sleep is associated with early signs of atherosclerosis in women
  • 2018
  • In: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 41:7
  • Journal article (peer-reviewed)abstract
    • Study Objectives: Although obstructive sleep apnea (OSA) is associated with overall cardiovascular disease and mortality, the association with atherosclerotic cardiovascular disease is less clear, especially in women. Recently, it has been suggested that OSA during rapid eye movement (REM) sleep, associated with long apneas and deep desaturations, could have severe cardiometabolic consequences. The aim of this study was to investigate whether OSA during REM sleep is associated with early signs of atherosclerosis in a population-based sample of women. Methods: In the community-based "Sleep and Health in Women" (SHE) cohort study, 400 women underwent polysomnography, anthropometric measurements, blood sampling, blood pressure measurement, and answered questionnaires. Ten years later, 201 of the original participants, free of known atherosclerotic disease at baseline and without continuous positive airway pressure treatment for OSA, underwent a high-frequency ultrasound of the common carotid artery to assess the individual thickness of the layers of the artery wall. Results: Severe OSA during REM sleep (REM apnea-hypopnea index [AHI] >= 30) was associated with a thicker intima. This association was still significant after adjustment for age, body mass index, alcohol, and smoking, as well as for further adjustment for systolic blood pressure, low-density lipoprotein, C-reactive protein, and diabetes (ss-coefficient, 0.008; p-value, 0.022). The association between a REM AHI of >= 30 and intima thickness was also seen in women with no or mild OSA and normal non-REM AHI. Conclusions: In this study of a community-based sample of women, severe OSA during REM sleep was independently associated with early signs of atherosclerosis. Statement of Significance Individuals with obstructive sleep apnea run an increased risk of cardiovascular disease, but the relationship between obstructive sleep apnea and atherosclerotic diseases is still unclear, especially in women. Sleep apnea and respiration deteriorate during rapid eye movement (REM)-sleep and sleep apnea during REM sleep might have severe adverse effects. In this study of a community-based sample of women, severe sleep apnea during REM sleep was associated with early signs of atherosclerosis, defined as increased intima thickness, at 10 years of follow-up. The association was also seen in women with low overall apnea-hypopnea index, normally not considered for treatment of sleep apnea. This suggests that occurrence of frequent obstructive apneas during REM sleep has to be taken into consideration when diagnosing and treating sleep apnea.
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47.
  • Ljunggren, Mirjam, et al. (author)
  • Rapid eye movement sleep apnea and carotid intima thickness in men and women : a SHE-MUSTACHE cohort study
  • 2022
  • In: Journal of Sleep Research. - : John Wiley & Sons. - 0962-1105 .- 1365-2869. ; 31:5
  • Journal article (peer-reviewed)abstract
    • Rapid eye movement (REM) obstructive sleep apnea might be particularly harmful to the cardiovascular system. We aimed to investigate the association between sleep apnea during REM sleep and signs of atherosclerotic disease in the form of carotid intima thickness in a community-based sample of men and women and possible sex differences in this association. The association between sleep apnea during REM sleep and intima thickness was analysed cross-sectionally in women from the community-based "Sleep and Health in Women" (SHE) study (n = 253) and age- and body mass index (BMI)-matched men from the "Men in Uppsala; a Study of sleep, Apnea and Cardiometabolic Health" (MUSTACHE) study (n = 338). Confounders adjusted for were age, BMI, gender, alcohol, and smoking. All participants underwent a full-night polysomnography, high-resolution ultrasonography of the common carotid artery, anthropometric measurements, blood pressure measurements, and answered questionnaires. There was an association between sleep apnea during REM sleep and thicker carotid intima that remained after adjustment for confounding (adjusted β = 0.008, p = 0.032). The intima was increased by 9.9% in the group with severe sleep apnea during REM sleep, and this association between severe sleep apnea during REM sleep and increased intima thickness remained after adjustment for confounders (adjusted β = 0.043, p = 0.021). More women than men had severe sleep apnea during REM sleep; moreover, in sex-stratified analyses, the association between sleep apnea during REM sleep and intima thickness was found in women but not in men. We conclude that severe REM sleep apnea is independently associated with signs of atherosclerosis. When stratified by sex, the association is seen in women but not in men.
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48.
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49.
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50.
  • Naessen, Tord, et al. (author)
  • Early postmenopausal hormone therapy improves postural balance
  • 2007
  • In: Menopause. - : Ovid Technologies (Wolters Kluwer Health). - 1072-3714 .- 1530-0374. ; 14:1, s. 14-19
  • Journal article (peer-reviewed)abstract
    • Objective: Postmenopausal hormone therapy (HT) results in more substantial reductions in the risk of hip fracture when initiated sooner rather than later after menopause. We studied the effects of postmenopausal HT on the postural balance of postmenopausal women, with further assessment according to the time since they achieved menopause. Design: One hundred women with a mean age of 52.5 years (91 evaluable) were randomly and blindly assigned to either a sequential estradiol-norethisterone acetate regimen or placebo for 3 months, after which all participants received open HT for a further 3 months. Postural balance was assessed as sway velocity using a force platform. Results: After 3 months of HT, sway velocity had improved (decreased) from baseline by 7.0% (P = 0.007 vs baseline and P = 0.038 vs placebo). Continued HT for 6 months further improved sway velocity by 12% from baseline (P < 0.0001) to reach values similar to those historically found in younger women or in postmenopausal women after long-term HT. Closer proximity to menopause and more pronounced increases in serum estradiol values were associated with stronger improvements in sway velocity (P = 0.018 for interaction). HT also improved dizziness (P = 0.016 vs baseline and 0.022 vs placebo). (Nonparametric statistics are used throughout, except for analyses of interaction and dizziness.) Conclusions: Initiation of HT soon after menopause rapidly improved postural balance to levels normally seen in young women. We suggest that improved postural balance can contribute to the protection against fractures associated with HT and explain the more substantial reduction in hip fracture risk after HT initiated sooner, compared with later, after menopause. Further study is required to confirm these results.
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