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| 4. |
- Fadl, Helena, 1965-, et al.
(författare)
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Changing diagnostic criteria for gestational diabetes in Sweden-a stepped wedge national cluster randomised controlled trial-the CDC4G study protocol
- 2019
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Ingår i: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The optimal criteria to diagnose gestational diabetes mellitus (GDM) remain contested. The Swedish National Board of Health introduced the 2013 WHO criteria in 2015 as a recommendation for initiation of treatment for hyperglycaemia during pregnancy. With variation in GDM screening and diagnostic practice across the country, it was agreed that the shift to new guidelines should be in a scientific and structured way. The aim of the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) in Sweden () is to evaluate the clinical and health economic impacts of changing diagnostic criteria for GDM in Sweden and to create a prospective cohort to compare the many long-term outcomes in mother and baby under the old and new diagnostic approaches. Methods This is a stepped wedge cluster randomised controlled trial, comparing pregnancy outcomes before and after the switch in GDM criteria across 11 centres in a randomised manner. The trial includes all pregnant women screened for GDM across the participating centres during January-December 2018, approximately two thirds of all pregnancies in Sweden in a year. Women with pre-existing diabetes will be excluded. Data will be collected through the national Swedish Pregnancy register and for follow up studies other health registers will be included. Discussion The stepped wedge RCT was chosen to be the best study design for evaluating the shift from old to new diagnostic criteria of GDM in Sweden. The national quality registers provide data on the whole pregnant population and gives a possibility for follow up studies of both mother and child. The health economic analysis from the study will give a solid evidence base for future changes in order to improve immediate pregnancy, as well as long term, outcomes for mother and child.
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| 5. |
- Valgeirsdóttir, Inga Rós, 1984-, et al.
(författare)
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Metformin as treatment of GDM
- 2023
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Whether metformin should be used as treatment for gestational diabetes mellitus (GDM) is a matter of controversy. Concerns about the effects on neonatal birth weight (mainly small for gestational age, SGA) have been raised in one randomized controlled trial in type 2 diabetes in pregnancy. [1] The aim of this study was to evaluate pregnancy outcomes based on different GDM treatment modalities with focus on metformin.Methods: A cohort study, based on data from the stepped wedge cluster randomized trial; CDC4G (Changing diagnostic criteria for GDM in Sweden - www.cdc4g.se). Screening for GDM involved repeated random plasma glucose measurements and/or clinical risk factors. [2] Data were collected from electronic case record forms, and national health and quality registers. Singleton pregnancies during 2018 (last birth in August 2019) from eight clusters were included. Women with pregestational diabetes and/or previous gastric bypass surgery were excluded. Pregnancy outcomes for different treatment regimens were analyzed for women with GDM compared to the background population without GDM. Logistic regression analyzes with adjustments for confounders (body mass index, age, smoking, country of birth, chronic hypertensive disease and cluster) was performed (adjusted odds ratio (aOR) with 95% confidence interval (CI)) for all outcomes. Results: Of the 54 678 pregnancies included, 2 169 (4.0%) were diagnosed with GDM; of whom 1 076 (49.6%) were treated with diet only (dGDM), 668 (30.8%) with metformin only (mGDM), 116 (5.3%) with insulin only (iGDM), and 309 (14.2%) with both metformin and insulin (miGDM). Pregnancy outcomes were as follows: SGA (10th percentile) was significantly decreased in the mGDM group [aOR 0.57 (95% CI 0.41-0.79)] compared to the background population and no significant difference was found in the miGDM group [aOR 0.78 (95% CI 0.51-1.18)] compared to the background population. No significant difference in SGA (10th percentile) was found in the dGDM group [aOR 1.02 (CI 0.83-1.25)] compared to the background population. There was significant difference in neonates born large for gestational age (LGA, 90th percentile) in both mGDM and miGDM groups compared to the background population [aOR 2.29 (95% CI 1.88-2.78) and aOR 2.32 (95% CI 1.76-3.07), respectively]. There was not significant difference in LGA (90th percentile) in dGDM compared to the background population [aOR 0.90 (95% CI 0.73-1.12].Conclusions: These preliminary unpublished results show no increase in SGA for metformin treated GDM compared to the background population. Outcomes in the diet treated GDM group were similar to the background population. Further analyzes are needed to compare outcomes between pharmacologic treatment groups and assess whether specific treatment regimens lead to similar outcomes in different subgroups (eg ethnicity, obesity and glucose values on diagnostic oral glucose tolerance test).References:1.Feig DS, Donovan LE, Zinman B, Sanchez JJ, Asztalos E, Ryan EA, et al. Metformin in women with type 2 diabetes in pregnancy (MiTy): a multicentre, international, randomised, placebo-controlled trial. The lancet Diabetes & endocrinology. 2020;8(10):834-44.2.Fadl H, Saeedi M, Montgomery S, Magnuson A, Schwarcz E, Berntorp K, et al. Changing diagnostic criteria for gestational diabetes in Sweden - a stepped wedge national cluster randomised controlled trial - the CDC4G study protocol. BMC pregnancy and childbirth. 2019;19(1):398.
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| 6. |
- Vikner, Pia, 1981, et al.
(författare)
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Att diagnostiseras med graviditetsdiabetes - påverkar det upplevelsen av graviditet, förlossning och amning?
- 2023
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Ingår i: Konferens Reproduktiv Hälsa 2023.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Graviditetsdiabetes uppkommer på grund av en ökad insulinresistens hos den gravida kvinnan. Sedan 2013 förespråkar WHO striktare diagnoskriterier för graviditetsdiabetes vilka även Socialstyrelsen rekommenderar sedan 2015. Trots rekommendationen används olika diagnoskriterier runtom i Sverige och förekomsten av graviditetsdiabetes varierar stort, allt från 1–22% (nationellt 6,2%). Att få diagnosen graviditetsdiabetes kan upplevas stigmatiserande och medföra ett ökat fokus på risker, övervakning och medicinska interventioner. Hur detta påverkar kvinnans upplevelse av graviditet, förlossning och amning är inte tillräckligt studerat. Syftet med studien är att undersöka om diagnosen graviditetsdiabetes påverkar kvinnans tillit till egen förmåga och känsla av sammanhang, hennes förlossningsupplevelse och tillit till egen förmåga att amma. Studien är en del av multicenterstudien CDC4G (ISRCTN 41918550) och förlossningsklinikerna i Örebro, Lund, Uppsala, Göteborg och Falun deltar. De kvinnor som enligt lokala riktlinjer för screening planeras för oralt glukostoleranstest (OGTT), kan tillfrågas om medverkan. Studien har etiktillstånd (2019–02080, 2020-00122). Studien pågår med insamling av enkäter som mäter känsla av sammanhang (SOC-13), tilltro till egen förmåga (GSE), förlossningsupplevelse (CEQ2) och tillit till egen förmåga att amma (BSE). Mätningarna sker före OGTT samt cirka åtta veckor postpartum. Jämförande analyser kommer att göras mellan svarande kvinnor som fått diagnosen (studiegrupp) med de som inte fått diagnosen (kontrollgrupp). Då diagnoskriterierna varierar på studieorterna kommer en andra kontrollgrupp bestå av kvinnor som inte fick diagnosen men vars resultat från OGTT överskred de rekommenderade diagnoskriterierna från Socialstyrelsen. Resultatet kommer att ge en ökad förståelse för om diagnosen graviditetsdiabetes påverkar kvinnans känsla av sammanhang och tilltro till egen förmåga under graviditet och amning samt fylla kunskapsluckan om diagnosen påverkar kvinnans förlossningsupplevelse. Slutsatserna kan bli ett viktigt bidrag i diskussionen om när och hur diagnosen graviditetsdiabetes ska användas under graviditet.
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| 8. |
- Behravesh, Masoud, et al.
(författare)
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A prospective study of the relationships between movement and glycemic control during day and night in pregnancy
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Both disturbed sleep and lack of exercise can disrupt metabolism in pregnancy. Accelerometery was used to objectively assess movement during waking (physical activity) and movement during sleeping (sleep disturbance) periods and evaluated relationships with continuous blood glucose variation during pregnancy. Data was analysed prospectively. 15-women without pre-existing diabetes mellitus wore continuous glucose monitors and triaxial accelerometers from February through June 2018 in Sweden. The relationships between physical activity and sleep disturbance with blood glucose rate of change were assessed. An interaction term was fitted to determine difference in the relationship between movement and glucose variation, conditional on waking/sleeping. Total movement was inversely related to glucose rate of change (p < 0.001, 95% CI (− 0.037, − 0.026)). Stratified analyses showed total physical activity was inversely related to glucose rate of change (p < 0.001, 95% CI (− 0.040, − 0.028)), whereas sleep disturbance was not related to glucose rate of change (p = 0.07, 95% CI (< − 0.001, 0.013)). The interaction term was positively related to glucose rate of change (p < 0.001, 95% CI (0.029, 0.047)). This study provides temporal evidence of a relationship between total movement and glycemic control in pregnancy, which is conditional on time of day. Movement is beneficially related with glycemic control while awake, but not during sleep.
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| 9. |
- Bengtsson, Anders, et al.
(författare)
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SLE och graviditet - en utmaning
- 2021
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Ingår i: ReumaBulletinen. - 2000-2246. ; 145:2, s. 28-31
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
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| 11. |
- Brodszki, Jana, et al.
(författare)
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Vascular mechanical properties and endothelial function in pre-eclampsia with special reference to bilateral uterine artery notch
- 2008
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 87:2, s. 154-162
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To assess whether women with pre-eclampsia (PE) have different properties of the blood vessel wall compared to healthy pregnant controls. Further, to evaluate endothelial function and vascular mechanical properties in women with PE with special regard to its association with bilateral uterine artery notch and placental histopathology. Participants. Some 57 Caucasian pregnant women: 23 with uncomplicated pregnancies and normal uterine artery Doppler, and 34 with PE, the PE group comprising 2 subgroups according to the presence (n=20) or absence (n=14) of bilateral uterine artery notches. Methods. Ultrasonic echo-tracking assessed the elastic properties of the common carotid artery, abdominal aorta and popliteal artery. Flow-mediated dilatation (FMD) of the brachial artery was measured by ultrasonography. Histopathological examination of the placenta was carried out in 46 pregnancies: 18 uncomplicated pregnancies, 15 with PE with bilateral notch, and 13 with PE without bilateral notch. Results. There were no significant differences in carotid, aortic or popliteal vessel wall stiffness either between women with PE and controls or within the PE group. FMD was significantly lower in women with PE than in controls (p=0.03). The lowest FMD was observed in pre-eclamptic women with bilateral uterine artery notches 9.5% (SD: 5.3) compared to 11.6% (SD: 5.4) in pre-eclamptic women without bilateral uterine artery notch, and 13.4% (SD: 4.0) in controls (p=0.01). Bilateral uterine artery notching was significantly associated with a lower FMD (OR: 0.87, 95% CI: 0.77-0.98). There were significantly more placentas with high ischaemic score in the bilateral notch group than in the group with PE and normal circulation. Conclusions. There were no differences in vessel wall stiffness between women with PE and healthy controls. Women with PE showed signs of endothelial dysfunction, significantly more pronounced in women with bilateral uterine artery notch. Bilateral uterine artery notch was associated with ischaemic pathology of the placenta. Notwithstanding, a significant number of placentas in the PE group failed to show noteworthy ischaemic or other morphological changes that could explain the role of the placenta in the development of PE.
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| 12. |
- de Brun, Maryam, 1991-, et al.
(författare)
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Changing diagnostic criteria for gestational diabetes (CDC4G) in Sweden : A stepped wedge cluster randomised trial
- 2024
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 21:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The World Health Organisation (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) has been criticised due to the limited evidence of benefits on pregnancy outcomes in different populations when switching from previously higher glycemic thresholds to the lower WHO-2013 diagnostic criteria. The aim of this study was to determine whether the switch from previous Swedish (SWE-GDM) to the WHO-2013 GDM criteria in Sweden following risk factor-based screening improves pregnancy outcomes.METHODS AND FINDINGS: A stepped wedge cluster randomised trial was performed between January 1 and December 31, 2018 in 11 clusters (17 delivery units) across Sweden, including all pregnancies under care and excluding preexisting diabetes, gastric bypass surgery, or multifetal pregnancies from the analysis. After implementation of uniform clinical and laboratory guidelines, a number of clusters were randomised to intervention (switch to WHO-2013 GDM criteria) each month from February to November 2018. The primary outcome was large for gestational age (LGA, defined as birth weight >90th percentile). Other secondary and prespecified outcomes included maternal and neonatal birth complications. Primary analysis was by modified intention to treat (mITT), excluding 3 clusters that were randomised before study start but were unable to implement the intervention. Prespecified subgroup analysis was undertaken among those discordant for the definition of GDM. Multilevel mixed regression models were used to compare outcome LGA between WHO-2013 and SWE-GDM groups adjusted for clusters, time periods, and potential confounders. Multiple imputation was used for missing potential confounding variables. In the mITT analysis, 47 080 pregnancies were included with 6 882 (14.6%) oral glucose tolerance tests (OGTTs) performed. The GDM prevalence increased from 595/22 797 (2.6%) to 1 591/24 283 (6.6%) after the intervention. In the mITT population, the switch was associated with no change in primary outcome LGA (2 790/24 209 (11.5%) versus 2 584/22 707 (11.4%)) producing an adjusted risk ratio (aRR) of 0.97 (95% confidence interval 0.91 to 1.02, p = 0.26). In the subgroup, the prevalence of LGA was 273/956 (28.8%) before and 278/1 239 (22.5%) after the switch, aRR 0.87 (95% CI 0.75 to 1.01, p = 0.076). No serious events were reported. Potential limitations of this trial are mainly due to the trial design, including failure to adhere to guidelines within and between the clusters and influences of unidentified temporal variations.CONCLUSIONS: In this study, implementing the WHO-2013 criteria in Sweden with risk factor-based screening did not significantly reduce LGA prevalence defined as birth weight >90th percentile, in the total population, or in the subgroup discordant for the definition of GDM. Future studies are needed to evaluate the effects of treating different glucose thresholds during pregnancy in different populations, with different screening strategies and clinical management guidelines, to optimise women's and children's health in the short and long term.TRIAL REGISTRATION: The trial is registered with ISRCTN (41918550).
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| 13. |
- Dereke, Jonatan, et al.
(författare)
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IgG4 subclass glutamic acid decarboxylase antibodies (GADA) are associated with a reduced risk of developing type 1 diabetes as well as increased C-peptide levels in GADA positive gestational diabetes.
- 2016
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Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616. ; 162, s. 45-48
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Tidskriftsartikel (refereegranskat)abstract
- Some women with gestational diabetes (GDM) present with autoantibodies associated with type 1 diabetes. These are usually directed against glutamic acid decarboxylase (GADA) and suggested to predict development of type 1 diabetes. The primary aim of this study was to investigate if GADA IgG subclasses at onset of GDM could assist in predicting postpartum development. Of 1225 women diagnosed with first-time GDM only 51 were GADA-positive. Total GADA was determined using ELISA. GADA subclasses were determined with radioimmunoassay. Approximately 25% of GADA-positive women developed type 1 diabetes postpartum. Titers of total GADA were higher in women that developed type 1 diabetes (142.1 vs 74.2u/mL; p=0.04) and they also had lower titers of GADA IgG4 (index=0.01 vs 0.04; p=0.03). In conclusion we found that that women with high titers of total GADA but low titers of GADA IgG4 were more prone to develop type 1 diabetes postpartum.
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| 14. |
- Dereke, Jonatan, et al.
(författare)
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Soluble CD163 and TWEAK in early pregnancy gestational diabetes and later glucose intolerance
- 2019
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Gestational diabetes mellitus (GDM) is today universally diagnosed during late pregnancy. Treating hyperglycaemia during pregnancy reduces the risk of complications, the effect of interventions is however limited due to the late diagnosis. It is thus important to identify biomarkers reaching a high precision for GDM development in early pregnancy. Here we aim to investigate soluble CD163 (sCD163) and soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) in early pregnancy GDM and their association to the development of later glucose intolerance. In this case-control study, women diagnosed with GDM in early pregnancy (n = 70) at Lund University Hospital, Lund, Sweden in 2011–2015 were age- and BMI matched to pregnant volunteers without diabetes (n = 70) recruited in early pregnancy from maternal health care centres in 2014–2015. Plasma levels of sCD163 and sTWEAK were analysed using commercial ELISA. Plasma levels of sCD163 did not differ between patients with and without GDM in early pregnancy (p = 0.86), plasma levels of sTWEAK however was decreased in women with GDM (0.71 [0.4–1.75] ng/ml) compared to controls (1.38 [0.63–4.86] ng/ml; p = 0.003). Women with sTWEAK levels in the lowest tertile had an increased risk of GDM in early pregnancy (p = 0.014). Neither sCD163 nor sTWEAK were associated with later glucose intolerance in women with GDM. This study reports decreased levels of sTWEAK in women with early pregnancy GDM, independent of age and BMI. Neither sCD163 nor sTWEAK were found to be associated to later glucose intolerance.
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| 15. |
- Elgaali, M, et al.
(författare)
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Female genital mutilation - an exported medical hazard
- 2005
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Ingår i: European Journal of Contraception & Reproductive Health Care. - : Informa UK Limited. - 1362-5187 .- 1473-0782. ; 10:2, s. 93-97
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Tidskriftsartikel (refereegranskat)abstract
- Background Female circumcision (FC) has remained a common practice in the countries where it has traditionally been performed. Following increased global mobility, it has also become a common medical issue in the predominantly non-Islamic countries where an increasing number of immigrants from regions where FC is still traditional, have settled. Objectives To investigate types of FC found in a group of immigrants from northern Africa with a current domicile in Scandinavia. To characterize these women with regard to education, socio-economic status and experienced complications and sequelae. To report attitudes to FC among the women and their husbands. Methods An autoquestionnaire was distributed to 220 immigrant women (16-42 years old), who belonged to an African community in Scandinavia and who had an been circumcised. Information was also gathered concerning 76 of their daughters (aged 1-13 years). Of the women's husbands, 95 were asked about their attitudes to FC. Results Of the 140 women, who had been circumcised in their home country before they migrated, 78 (35%) had been clitoridectomized, 38 (17%) had been subjected to genital excision and 24 (11%) to infibulation. The corresponding percentages in the remaining women, who had had FC when returning home for a visit, were 0%, 14% and 22%, respectively. Of the daughters, 15 (19%) had been circumcised whilst living in Scandinavia; all had been clitoridectornized. Twenty-eight (13%) women reported having experienced late complications or post-FC sequelae. A positive attitude to stopping the tradition of FC was reported twice as often by the husbands (69%) as by the circumcised women (35%). Religion (95% of the responders were Muslims and 5% Christians), cultural tradition, and increased chance of marriage or of continued health were the reasons put for-ward in favor of the continuation of FC by 58%, 27%, 10% and 4%, respectively. Five per cent could not supply an opinion. Conclusions FC is performed in immigrant women even after settling in areas where this practise is legally banned. Circumcised immigrant women experience medical and sexual problems which have to be dealt with in their new domicile country. Many African Islamic women, who have migrated to Scandinavia, seem still to be in favour of the continuation of circumcision for varying reasons.
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| 16. |
- Hertig, Alexandre, et al.
(författare)
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How should women with pre-eclampsia be followed up? New insights from mechanistic studies
- 2008
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Ingår i: Nature Clinical Practice Nephrology. - : Springer Science and Business Media LLC. - 1745-8323 .- 1745-8331. ; 4:9, s. 503-509
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Forskningsöversikt (refereegranskat)abstract
- Understanding of the maternal syndrome of pre-eclampsia has greatly improved over the past 5 years. Specifically, the notion has emerged that the placenta is a source of antiangiogenic factors, such as soluble fms-like tyrosine kinase 1, that can progressively impair the mother's vascular and glomerular function throughout pregnancy. This impairment can be harmless during normal pregnancy, but in cases of defective placentation, concentrations of antiangiogenic factors increase to a level that compromises vital vascular functions in the short term and jeopardizes long-term maternal and fetal outcomes. In both pre-eclamptic and healthy pregnancies, the transient imbalance between angiogenic and antiangiogenic factors elicited by pregnancy acts as a 'stress test' for the endothelium, particularly in the glomerular capillary bed. Women who do not pass this test (i.e. those who develop pre-eclampsia or gestational hypertension) should be screened for glomerular disease, and their cardiovascular risk should be carefully monitored throughout life.
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| 17. |
- Ishchuk, Olena P., et al.
(författare)
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The use of polyhydroxylated carboxylic acids and lactones to diminish biofilm formation of the pathogenic yeast : Candida albicans
- 2019
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Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 9:19, s. 10983-10989
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Tidskriftsartikel (refereegranskat)abstract
- The vaginal microbiome of healthy women is a diverse and dynamic system of various microorganisms. Any sudden change in microbe composition can increase the vaginal pH and thus lead to vaginal infections, conditions that affect a large percentage of women each year. The most common fungal strains involved in infections belong to the yeast species Candida albicans. The main virulence factor of C. albicans is the ability to transform from planktonic yeast-form cells into a filamentous form (hyphae or pseudohyphae), with the subsequent formation of biofilm. The hyphal form, constituted by filamentous cells, has the ability to invade tissue and induce inflammation. Our hypothesis is that certain polyhydroxylated carboxylic acids, that may serve as an alternative carbohydrate source and at the same time lower the pH, function as an indicator of a nutrient-rich environment for C. albicans, which favors planktonic cells over hyphae, and thus diminish the formation of biofilm. We have shown that the biofilm formation in C. albicans and other Candida species can be significantly reduced by the addition of glucono-δ-lactone (GDL).
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| 18. |
- Kappers, Mariette H W, et al.
(författare)
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The Vascular Endothelial Growth Factor Receptor Inhibitor Sunitinib Causes a Preeclampsia-Like Syndrome With Activation of the Endothelin System.
- 2011
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Ingår i: Hypertension. - 1524-4563. ; 58, s. 295-351
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Tidskriftsartikel (refereegranskat)abstract
- Angiogenesis inhibition is an established treatment for several tumor types. Unfortunately, this therapy is associated with adverse effects, including hypertension and renal toxicity, referred to as "preeclampsia." Recently, we demonstrated in patients and in rats that the multitarget tyrosine kinase inhibitor sunitinib induces a rise in blood pressure (BP), renal dysfunction, and proteinuria associated with activation of the endothelin system. In the current study we investigated the effects of sunitinib on rat renal histology, including the resemblance with preeclampsia, as well as the roles of endothelin 1, decreased nitric oxide (NO) bioavailability, and increased oxidative stress in the development of sunitinib-induced hypertension and renal toxicity. In rats on sunitinib, light and electron microscopic examination revealed marked glomerular endotheliosis, a characteristic histological feature of preeclampsia, which was partly reversible after sunitinib discontinuation. The histological abnormalities were accompanied by an increase in urinary excretion of endothelin 1 and diminished NO metabolite excretion. In rats on sunitinib alone, BP increased (ΔBP: 31.6±0.9 mm Hg). This rise could largely be prevented with the endothelin receptor antagonist macitentan (ΔBP: 12.3±1.5 mm Hg) and only mildly with Tempol, a superoxide dismutase mimetic (ΔBP: 25.9±2.3 mm Hg). Both compounds could not prevent the sunitinib-induced rise in serum creatinine or renal histological abnormalities and had no effect on urine nitrates but decreased proteinuria and urinary endothelin 1 excretion. Our findings indicate that both the endothelin system and oxidative stress play important roles in the development of sunitinib-induced proteinuria and that the endothelin system rather than oxidative stress is important for the development of sunitinib-induced hypertension.
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| 19. |
- Kristensen, Karl, et al.
(författare)
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Cystatin C, beta-2-microglobulin and beta-trace protein in pre-eclampsia
- 2007
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 86:8, s. 921-926
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Tidskriftsartikel (refereegranskat)abstract
- Background. An altered renal function is an essential component of the patho-physiology of pre-eclampsia. The plasma levels of low molecular mass proteins, e. g. beta-trace protein, beta-2-microglobulin and cystatin C, are increased in the third trimester of normal pregnancy. The plasma levels of cystatin C and beta-2-microglobulin are further increased in preeclampsia, and the cystatin C level has been reported to be a reliable marker for the disease. The aim of this investigation was to study the plasma levels of beta-trace protein, beta-2-microglobulin and cystatin C in pre-eclampsia, and to determine the diagnostic performance of these proteins compared to that of urate and creatinine. Methods. A case-control study of 57 women diagnosed with pre-eclampsia, and 218 healthy women with uncomplicated singleton pregnancies in the third trimester. Women in the catchment area of Lund, Sweden, were included during an 18-month period from October 2003 to April 2005. Venous blood samples were drawn upon inclusion when diagnosis was made. The maternal plasma concentrations of the 3 proteins were analysed by automated particle-enhanced immunoturbidimetric assays. Results. The plasma levels of the 3 proteins were significantly higher in the third trimester of pre-eclamptic patients compared to healthy pregnant women in the third trimester. The upper reference limits ( parametric 97.5 percentile) were 2.57 mg/l for beta-2-microglobulin, 0.72 mg/l for beta-trace protein and 1.37 mg/l for cystatin C. ROC analysis showed similar diagnostic performance for the 3 proteins, with b-trace protein displaying the best diagnostic performance of all the analytes. Conclusions. In this study, the maternal plasma levels of beta 2-microglobulin, beta-trace protein and cystatin C were all significantly elevated in pre-eclampsia compared to those of healthy pregnant women, and displayed similar diagnostic performance for diagnosing pre-eclampsia. The results indicate that low molecular mass proteins are useful as markers of renal impairment in pre-eclampsia.
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| 20. |
- Kristensen, Karl, et al.
(författare)
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Increased plasma levels of ss(2)-microglobulin, cystatin C and ss-trace protein in term pregnancy are not due to utero-placental production.
- 2008
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68, s. 649-653
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Tidskriftsartikel (refereegranskat)abstract
- Objective . To study concentration gradients of the low molecular mass proteins, ss(2)-microglobulin, cystatin C and ss-trace protein, between the uterine and ante-cubital veins, the umbilical artery and vein and in the amniotic fluid compartment. Material and methods. The study comprised 27 healthy women with uncomplicated pregnancies undergoing caesarean section at term. Samples were collected simultaneously and paired t-tests were used to compare mean plasma concentrations. Results . There was no significant concentration gradient in the plasma levels of ss(2)-microglobulin, cystatin C or ss-trace protein between the uterine and antecubital veins. There were no correlations between the protein levels in the compartments. Conclusion . The utero-placental unit does not contribute significantly to the maternal levels of ss(2)-microglobulin, cystatin C and ss-trace protein in normal pregnancy, and the proteins are not likely to be transferred across the placental barrier.
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| 21. |
- Kristensen, Karl, et al.
(författare)
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Serum Amyloid A Protein and C-Reactive Protein in Normal Pregnancy and Preeclampsia.
- 2009
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Ingår i: Gynecologic and Obstetric Investigation. - : S. Karger AG. - 1423-002X .- 0378-7346. ; 67:4, s. 275-280
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To study plasma levels of serum amyloid A protein and C-reactive protein in pregnant women with and without preeclampsia and non-pregnant women. Plasma levels of haptoglobin, orosomucoid and ceruloplasmin were also analyzed. Methods: The study included 295 women with uncomplicated pregnancies, 57 women diagnosed with preeclampsia, and 58 healthy non-pregnant women. Plasma concentrations of acute phase proteins were analyzed by particle-enhanced immunoassays. Non-parametric Kruskal-Wallis and Mann-Whitney U tests were used to test differences between the groups. Results: Plasma levels of C-reactive protein and ceruloplasmin were increased in pregnant women with and without preeclampsia compared to non-pregnant women. Plasma levels of serum amyloid A protein and C-reactive protein were not elevated in women with preeclampsia compared to women with normal pregnancy. Conclusion: The description of preeclampsia as a systemic inflammatory state was not reflected in the plasma levels of serum amyloid A protein and C-reactive protein.
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| 22. |
- Kristensen, Karl, et al.
(författare)
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Temporal changes of the plasma levels of cystatin C, beta-trace protein, beta(2)-microglobulin, urate and creatinine during pregnancy indicate continuous alterations in the renal filtration process
- 2007
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 67:6, s. 612-618
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To determine the plasma levels of the renal functional markers creatinine, urate, cystatin C, beta(2)-microglobulin and beta-trace protein in samples from the first, second, early third and late third trimesters of 398 healthy women with uncomplicated singleton pregnancies. Material and methods. Plasma samples from 58 healthy non-pregnant women served as controls. The creatinine levels were significantly lower at all time-points in pregnancy, whereas the urate levels were lower during the first and second trimesters but increased in the late third trimester. The cystatin C, beta(2)-microglobulin and beta-trace protein levels displayed similar changes with increased levels in the third trimester but unaltered levels during the first and second trimesters. Results. The results indicate an increased filtration of low-molecular weight molecules during pregnancy, particularly during the first and second trimesters, whereas filtration of 10-30 kDa molecules is decreased in the third but unaltered in the first and second trimesters. The levels of albumin and alpha(2)-macroglobulin were measured in the same samples. Conclusions. The albumin levels decreased in the second and third trimesters, whereas the levels of alpha(2)-macroglobulin were unchanged, which is compatible with a virtually unaltered transfer of alpha(2)-macroglobulin between the intra-and extravascular space during pregnancy and a significantly increased extravascular fraction of albumin.
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| 23. |
- Latham-Cork, Harriett C., et al.
(författare)
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A novel non-antimicrobial treatment of bacterial vaginosis : An open label two-private centre study
- 2021
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Ingår i: European Journal of Obstetrics and Gynecology and Reproductive Biology. - : Elsevier BV. - 0301-2115. ; 256, s. 419-424
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bacterial vaginosis (BV) is the most common cause of vaginal discharge. It is caused by an imbalance in the normal vaginal microbiota. Symptoms include an offensive odour. Standard oral or vaginal antimicrobial treatments have high immediate cure rates but almost as high recurrence rates. pHyph, a vaginal pessary, contains glucono-delta-lactone (GDL) and sodium gluconate (NaG) which restore normal pH and disrupt the associated biofilm. Aim: To investigate the clinical performance of pHyph, for both treatment and recurrence prevention. Design An open-label, single arm, multi-centre first in women study. Setting: Two private gynaecology clinics in Skåne County, Southern Sweden. Methods: Twenty four adult women with confirmed bacterial vaginosis received the investigational product for self-administration on days 0, 2, 4, and 6 and were assessed on day 7. Clinical cure was defined as absence of three of four Amsel's criteria (pH excluded) on day 7. Safety and tolerability were also recorded. Those not cured by day 7 received a prolonged treatment protocol. Results There were three withdrawals, two before the day 7 assessment. 18/22 (82 %) were clinically cured at day 7. The pessary was well tolerated. Recurrence rates at 14 days in patients cured at day 7 after receiving standard study treatment (n = 18) were 1/18 (5.6 %) with no additional recurrences reported at 35 days. Three of four patients not cured at 7 days received continued treatment (day 7, 9, 11, and 13), but none were cured at 14 days. Conclusion: pHyph has the potential for both high cure rates and a reduction in recurrence.
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| 24. |
- Malmgren, Linnea, et al.
(författare)
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The complexity of kidney disease and diagnosing it - Cystatin C, selective glomerular hypofiltration syndromes and proteome regulation.
- 2023
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 293:3, s. 293-308
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Tidskriftsartikel (refereegranskat)abstract
- Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous GFR-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterised by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules < 1kDa dominating the glomerular filtrate e.g., water, urea, creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterised by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.
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| 25. |
- Mistry, Hiten D., et al.
(författare)
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Evidence of Augmented Intrarenal Angiotensinogen Associated With Glomerular Swelling in Gestational Hypertension and Preeclampsia : Clinical Implications
- 2019
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 8:13
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Tidskriftsartikel (refereegranskat)abstract
- Background AGT (angiotensinogen) synthesis occurs in renal proximal tubular epithelial cells, independent from systemic AGT , as a component of the intrarenal renin-angiotensin system. We investigated urinary AGT , as a biomarker for renin-angiotensin system activation, and electrolyte concentrations, in relation to glomerular volume, as a proxy for glomerular endotheliosis in renal biopsy tissue from pregnant normotensive control and hypertensive women. Methods and Results Urine samples were collected from normotensive control (n=10), gestational hypertensive (n=6), and pre-eclamptic (n=16) women at the time a renal biopsy was obtained. Samples were collected from Lund University Hospital between November 1999 and June 2001. Urinary AGT , potassium, and sodium were measured, normalized to urinary creatinine. Mean glomerular volume was estimated from biopsy sections. AGT protein expression and localization were assessed in renal biopsies by immunohistochemistry. Urinary AGT concentrations were higher in hypertensive pregnancies (median, gestational hypertension: 11.3 ng/mmol [interquartile range: 2.8-13.6]; preeclampsia: 8.4 ng/mmol [interquartile range: 4.2-29.1]; normotensive control: 0.6 ng/mmol [interquartile range: 0.4-0.8]; P<0.0001) and showed a positive relationship with estimated mean glomerular volume. Urinary potassium strongly correlated with urinary AGT ( P<0.0001). Although numbers were small, AGT protein was found in both glomeruli and proximal tubules in normotensive control but was present only in proximal tubules in women with hypertensive pregnancy. Conclusions This study shows that pregnant women with gestational hypertension or preeclampsia have increased urinary AGT and potassium excretion associated with signs of glomerular swelling. Our data suggest that the kidneys of women with hypertensive pregnancies and endotheliosis have inappropriate intrarenal renin-angiotensin system activation, which may contribute toward the pathogenesis of hypertension and renal injury.
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