| 1. |
- Fransson, Kristin, et al.
(författare)
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Miljöhandbokför upphandlare
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Hållbar utveckling innefattar såväl social, ekonomisk som miljömässig hållbar utveckling.I Miljöhandboken kommer dessa tre aspekter av hållbar utveckling att behandlas,dock ligger störst fokus på miljöaspekterna.Miljöhandboken ska hjälpa upphandlare att ställa relevanta miljökrav vid upphandlingoch är ett komplement till exempelvis Konkurrensverkets (f.d. Miljöstyrningsrådets)upphandlingskriterier och ska bidra med fakta kring hur miljökrav kan ställas.Miljökrav vid upphandling kan innefatta bl. a. energianvändning, livslängd, skadligaämnen, strålning, återvinning och miljöledningssystem. Kravens betydelse påverkasbl. a. av upphandlingens omfattning och miljömognaden inom produktsegmentet. Imiljöhandboken presenteras inga specifika kriterier eller gränsvärden för olika miljöaspekter,i stället ges länkar till exempelvis lagstiftning, myndigheter och miljömärkningar.Detta för att kriterier och gränsvärden uppdateras kontinuerligt som en följdav teknikutveckling men också för att den samlade kunskapen om vad som är miljöproblemständigt växer och kan ge upphov till nya kriterier och gränsvärden. Tyngdpunkteni denna handbok ligger på miljöpåverkan ur ett livscykelperspektiv, vilket innebäratt hänsyn tas till miljöpåverkan från utvinning av råmaterial till resthantering aven produkt.
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| 2. |
- Yang, Fen, et al.
(författare)
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Association of Maternal Preeclampsia With Offspring Risks of Ischemic Heart Disease and Stroke in Nordic Countries
- 2022
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:11
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE An association between maternal preeclampsia and an increased risk of cardiovascular disease in the offspring is plausible, but evidence in this area is limited. OBJECTIVE To investigate (1) the association between maternal preeclampsia and risks of ischemic heart disease (IHD) and stroke in the offspring, (2) whether the association varies by severity or timing of onset of preeclampsia, and (3) the role of preterm birth and small for gestational age (SGA) birth, both of which are related to preeclampsia and cardiovascular diseases, in this association. DESIGN, SETTING, AND PARTICIPANTS This multinational population-based cohort study obtained data from Danish, Finnish, and Swedish national registries. Live singleton births from Denmark (1973-2016), Finland (1987-2014), and Sweden (1973-2014) were followed up until December 31, 2016, in Denmark and December 31, 2014, in Finland and Sweden. Data analyses were performed between September 2020 and September 2022. EXPOSURES Preeclampsia and its subtypes, including early onset (<34 gestational weeks) and late onset (>= 34 gestational weeks), severe and mild or moderate, and with and without SGA birth. MAIN OUTCOMES AND MEASURES Diagnoses of IHD and stroke were extracted from patient and cause-of-death registers. Cox proportional hazards regression models and flexible parametric survival models were used to analyze the associations. Sibling analyses were conducted to control for unmeasured familial factors. RESULTS The cohort included of 8 475 819 births (2 668 697 [31.5%] from Denmark, 1636 116 [19.3%] from Finland, and 4171006 [49.2%] from Sweden, comprising 4350 546 boys [51.3%]). Of these offspring, 188 670 (2.2%) were exposed to maternal preeclampsia, 7446 (0.1%) were diagnosed with IHD, and 10 918 (0.1%) were diagnosed with stroke during the median (IQR) follow-up of 19.3 (9.0-28.1) years. Offspring of individuals with preeclampsia had increased risks of IHD (adjusted hazard ratio [HR], 1.33; 95% CI, 1.12-1.58) and stroke (adjusted HR, 1.34; 95% CI, 1.17-1.52). These associations were largely independent of preterm or SGA birth. Severe forms of preeclampsia were associated with a higher stroke risk than less severe forms (severe vs mild or moderate: adjusted HR, 1.81[95% CI, 1.41-2.32] vs 1.22 [95% CI, 1.05-1.42]; early vs late onset: adjusted HR, 2.55 [95% CI, 1.97-3.28] vs 1.18 [95% CI, 1.01-1.39]; with vs without SGA birth: adjusted HR, 1.84 [95% CI, 1.44-2.34] vs 1.25 [95% CI, 1.07-1.48]). Sibling analyses suggested that the associations were partially explained by unmeasured familial factors. CONCLUSIONS AND RELEVANCE Results of this study suggest that offspring born to individuals with preeclampsia had increased IHD and stroke risk that were not fully explained by preterm or SGA birth, and that the associated risks for stroke were higher for severe forms of preeclampsia.
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| 3. |
- Adman, Per, et al.
(författare)
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171 forskare: ”Vi vuxna bör också klimatprotestera”
- 2019
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Ingår i: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
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| 4. |
- Colmorn, Lotte B., et al.
(författare)
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Mode of first delivery and severe maternal complications in the subsequent pregnancy
- 2017
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 96:9, s. 1053-1062
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Severe obstetric complications increase with the number of previous cesarean deliveries. In the Nordic countries most women have two children. We present the risk of severe obstetric complications at the delivery following a first elective or emergency cesarean and the risk by intended mode of second delivery. Material and methods: A two-year population-based data collection of severe maternal complications in women with two deliveries in the Nordic countries (n = 213 518). Denominators were retrieved from the national medical birth registers. Results: Of 35 450 first cesarean deliveries (17%), 75% were emergency and 25% elective. Severe complications at second delivery were more frequent in women with a first cesarean than with a first vaginal delivery, and rates of abnormally invasive placenta, uterine rupture and severe postpartum hemorrhage were higher after a first elective than after a first emergency cesarean delivery [relative risk (RR) 4.1, 95% confidence intervals (CI) 2.0-8.1; RR 1.8, 95% CI 1.3-2.5; RR 2.3, 95% CI 1.5-3.5, respectively]. A first cesarean was associated with up to 97% of severe complications in the second pregnancy. Induction of labor was associated with an increased risk of uterine rupture and severe hemorrhage. Conclusion: Elective repeat cesarean can prevent complete uterine rupture at the second delivery, whereas the risk of severe obstetric hemorrhage, abnormally invasive placenta and peripartum hysterectomy is unchanged by the intended mode of second delivery in women with a first cesarean. Women with a first elective vs. an emergency cesarean have an increased risk of severe complications in the second pregnancy.
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| 5. |
- Colmorn, Lotte B., et al.
(författare)
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The Nordic Obstetric Surveillance Study: a study of complete uterine rupture, abnormally invasive placenta, peripartum hysterectomy, and severe blood loss at delivery
- 2015
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 94:7, s. 734-744
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the rates and characteristics of women with complete uterine rupture, abnormally invasive placenta, peripartum hysterectomy, and severe blood loss at delivery in the Nordic countries. Design: Prospective, Nordic collaboration. Setting: The Nordic Obstetric Surveillance Study (NOSS) collected cases of severe obstetric complications in the Nordic countries from April 2009 to August 2012. Sample and methods: Cases were reported by clinicians at the Nordic maternity units and retrieved from medical birth registers, hospital discharge registers, and transfusion databases by using International Classification of Diseases, 10th revision codes on diagnoses and the Nordic Medico-Statistical Committee Classification of Surgical Procedure codes. Main outcome measures: Rates of the studied complications and possible risk factors among parturients in the Nordic countries. Results: The studied complications were reported in 1019 instances among 605362 deliveries during the study period. The reported rate of severe blood loss at delivery was 11.6/10000 deliveries, complete uterine rupture was 5.6/10000 deliveries, abnormally invasive placenta was 4.6/10000 deliveries, and peripartum hysterectomy was 3.5/10000 deliveries. Of the women, 25% had two or more complications. Women with complications were more often >35years old, overweight, with a higher parity, and a history of cesarean delivery compared with the total population. Conclusion: The studied obstetric complications are rare. Uniform definitions and valid reporting are essential for international comparisons. The main risk factors include previous cesarean section. The detailed information collected in the NOSS database provides a basis for epidemiologic studies, audits, and educational activities.
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| 6. |
- Grabowski, Pawel, 1975-, et al.
(författare)
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Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status
- 2005
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 105:12, s. 4807-4812
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Tidskriftsartikel (refereegranskat)abstract
- B-cell chronic lymphocytic leukemia (CLL) consists of 2 prognostic entities where cases with mutated immunoglobulin VH genes have better outcome than unmutated cases. VH-mutated CLLs display longer telomeres compared with unmutated cases and telomere length has been indicated to predict outcome, although the prognostic value of telomere length has not been fully established in CLL. We analyzed telomere length, VH gene mutation status, and clinical parameters in a large series of CLL. Telomere length was assessed by quantitative polymerase chain reaction (PCR), giving a very good correlation to telomere length estimated by Southern blotting (P < .001). The prognostic information given by mutation status (n = 282) and telomere length (n = 246) was significant (P < .001, respectively). Telomere length was a prognostic factor for stage A (P = .021) and stage B/C (P = .018) patients, whereas mutation status predicted outcome only in stage A patients (P < .001). Furthermore, mutated CLLs were subdivided by telomere length into 2 groups with different prognoses (P = .003), a subdivision not seen for unmutated cases (P = .232). Interestingly, the VH-mutated group with short telomeres had an overall survival close to that of the unmutated cases. Thus, by combining VH mutation status and telomere length, an improved subclassification of CLL was achieved identifying previously unrecognized patient groups with different outcomes.
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| 7. |
- Jakobsson, Maija, et al.
(författare)
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Emergency peripartum hysterectomy: results from the prospective Nordic Obstetric Surveillance Study (NOSS)
- 2015
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 94:7, s. 745-754
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the prevalence and risk factors of emergency peripartum hysterectomy. Design:Nordic collaborative study. Population605362 deliveries across the five Nordic countries. Methods: We collected data prospectively from patients undergoing emergency peripartum hysterectomy within 7days of delivery from medical birth registers and hospital discharge registers. Control populations consisted of all other women delivering on the same units during the same time period. Main outcome measures: Emergency peripartum hysterectomy rate. Results: The total number of emergency peripartum hysterectomies reached 211, yielding an incidence rate of 3.5/10000 (95% confidence interval 3.0-4.0) births. Finland had the highest prevalence (5.1) and Norway the lowest (2.9). Primary indications included an abnormally invasive placenta (n=91, 43.1%), atonic bleeding (n=69, 32.7%), uterine rupture (n=31, 14.7%), other bleeding disorders (n=12, 5.7%), and other indications (n=8, 3.8%). The delivery mode was cesarean section in nearly 80% of cases. Previous cesarean section was reported in 45% of women. Both preterm and post-term birth increased the risk for emergency peripartum hysterectomy. The number of stillbirths was substantially high (70/1000), but the case fatality rate stood at 0.47% (one death, maternal mortality rate 0.17/100000 deliveries). Conclusions: A combination of prospective data collected from clinicians and information gathered from register-based databases can yield valuable data, improving the registration accuracy for rare, near-miss cases. However, proper and uniform clinical guidelines for the use of well-defined international diagnostic codes are still needed.
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| 8. |
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| 9. |
- Langhoff-Roos, Jens, et al.
(författare)
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The Nordic medical birth registers - a potential goldmine for clinical research
- 2014
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 93:2, s. 132-137
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Nordic medical birth registers have long been used for valuable clinical research. Their collection of data for more than four decades offers unusual possibilities for research across generations. At the same time, serum and blotting paper blood samples have been stored from most neonates. Two large cohorts (approximately 100000 births) in Denmark and Norway have been described by questionnaires, interviews and collection of biological samples (blood, urine and milk teeth), as well as a systematic prospective follow-up of the offspring. National patient registers provide information on preceding, underlying and present health problems of the parents and their offspring. Researchers may, with permission from the national authorities, obtain access to individualized or anonymized data from the registers and tissue-banks. These data allow for multivariate analyses but their usefulness depends on knowledge of the specific registers and biological sample banks and on proper validation of the registers.
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| 10. |
- Petersson, Malin, et al.
(författare)
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Patient-reported symptom severity in a nationwide myasthenia gravis cohort : cross-sectional analysis of the Swedish GEMG study
- 2021
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 97:14, s. e1382-e1391
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: To describe myasthenia gravis activities of daily living (MG-ADL) in relation to clinical characteristics in a large Swedish nationwide cohort.Methods: In a cross-sectional prevalence cohort study, the Genes and Environment in Myasthenia Gravis study, performed from November 2018 through August 2019, patients with myasthenia gravis (MG) were invited to submit an extensive 106-item life environment questionnaire, including the MG-ADL score. Patients were classified into early-onset MG (EOMG, <50 years), late-onset MG (LOMG, >= 50 years), or thymoma-associated MG (TAMG). Comparisons of disease-specific characteristics were made between subgroups, sexes, and different MG-ADL scores.Results: A total of 1,077 patients were included, yielding a 74% response rate: 505 (47%) were classified as EOMG, 520 (48%) LOMG, and 45 (4%) TAMG. Mean age at inclusion was 64.3 years (SD 15.7) and mean disease duration was 14.6 years (SD 14.0). Complete MG-ADL scores (n = 1,035) ranged from 0p to 18p, where 26% reported a score of 0p. Higher MG-ADL scores were associated with female sex, obesity, and diagnostic delay (odds ratio [OR] 1.62, 1.72, and 1.69; p(adj) = 0.017, 0.013, and 0.008) and inversely correlated with high educational attainment (OR 0.59; p(adj) = 0.02), but not with age at inclusion, disease subtype, or disease duration. Almost half of the population (47%) reported MG-ADL >= 3p, corresponding to an unsatisfactory symptom state.Discussion: In this nationwide study, comprising more than 40% of the prevalent MG population in Sweden, almost half of the patients reported current disease symptoms associated with an unsatisfactory symptom state, indicating the need for improved treatment options.
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| 11. |
- Smedby, Karin Ekström, et al.
(författare)
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Ultraviolet radiation exposure and risk of malignant lymphomas
- 2005
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 97:3, s. 199-209
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The incidence of malignant lymphomas has been increasing rapidly, but the causes of these malignancies remain poorly understood. One hypothesis holds that exposure to ultraviolet (UV) radiation increases lymphoma risk. We tested this hypothesis in a population-based case-control study in Denmark and Sweden. METHODS: A total of 3740 patients diagnosed between October 1, 1999, and August 30, 2002, with incident malignant lymphomas, including non-Hodgkin lymphoma, chronic lymphocytic leukemia, and Hodgkin lymphoma, and 3187 population controls provided detailed information on history of UV exposure and skin cancer and information on other possible risk factors for lymphomas. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by logistic regression. Statistical tests were two-sided. RESULTS: Multivariable-adjusted analyses revealed consistent, statistically significant negative associations between various measures of UV light exposure and risk of non-Hodgkin lymphoma. A high frequency of sun bathing and sunburns at age 20 years and 5-10 years before the interview and sun vacations abroad were associated with 30%-40% reduced risks of non-Hodgkin lymphoma (e.g., for sunbathing four times a week or more at age 20 versus never sunbathing, OR = 0.7, 95% CI = 0.6 to 0.9; for two or more sunburns a year at age 20 versus no sunburns, OR = 0.6, 95% CI = 0.5 to 0.8). These inverse associations increased in strength with increasing levels of exposure (all P(trend)< or =.01). Similar, albeit weaker, associations were observed for Hodgkin lymphoma. There were no clear differences among non-Hodgkin lymphoma subtypes, although associations were stronger for B-cell than for T-cell lymphomas. A history of skin cancer was associated with a doubling in risks of both non-Hodgkin and Hodgkin lymphoma. CONCLUSIONS: A history of high UV exposure was associated with reduced risk of non-Hodgkin lymphoma. The positive association between skin cancer and malignant lymphomas is, therefore, unlikely to be mediated by UV exposure.
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| 12. |
- Tobin, Gerard, et al.
(författare)
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Patients with chronic lymphocytic leukemia with mutated VH genes presenting with Binet stage B or C form a subgroup with a poor outcome
- 2005
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Ingår i: Haematologica. - 0390-6078 .- 1592-8721. ; 90:4, s. 465-469
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives. The immunoglobulin VH gene mutation status is a strong prognostic indicator in B-cell chronic lymphocytic leukemia (CLL), since unmutated VH genes are correlated with short survival. However, the traditional cut-off level dividing mutated and unmutated cases, i.e. more or less than 2% mutations, has been questioned and other cut-offs have been suggested. We investigated whether an alternative cut-off should be applied and the relation of mutational status to another prognostic marker, Binet staging. Design and Methods. VH gene mutation status was assessed in 332 CLL cases by polymerase chain reaction amplification and nucleotide sequencing and was further correlated with overall survival using different VH mutation cut-offs (1-7%) and Binet stage. Results. After testing different mutation borders, the 2% cut-off remained the best discriminative level for determining prognosis. Interestingly, prognostic stratification was improved by combining the information on VH gene mutation status with that of Binet stage: unmutated cases (all stages, n=151, mutated cases with stage A (n=77), and mutated cases with stage B or C (n=37) had a median survival of 82, 179 and 74 months, respectively. Interpretation and Conclusions. CLL cases displaying mutated VH genes with Binet stage B or C had a survival similar to that of unmutated cases and significantly shorter than that of mutated stage A CLL. Our result reveals clinical heterogeneity within the VH mutated CLL group by inclusion of Binet stage data, a finding which is of importance when considering surrogate marker(s) for VH mutation status. ©2005 Ferrata Storti Foundation.
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| 13. |
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| 14. |
- Walsh, Sarah H, et al.
(författare)
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Telomere length and correlation with histopathogenesis in B-cell leukemias/lymphomas
- 2007
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 78:4, s. 283-289
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Tidskriftsartikel (refereegranskat)abstract
- Telomere length was recently reported to correlate with cellular origin of B-cell malignancies in relation to the germinal center (GC). In this report, we measured telomere length by quantitative-PCR in 223 B-cell lymphomas/leukemias and correlated results with immunoglobulin (Ig) mutation status and immunostainings for GC/non-GC subtypes of diffuse large B-cell lymphoma (DLBCL). Shortest telomeres were found in Ig-unmutated chronic lymphocytic leukemia (CLL) [median telomere to single copy gene value (T/S) 0.33], differing significantly to Ig-mutated CLL (0.63). Contrary to this, mantle cell lymphomas (MCLs) exhibited similar telomere lengths regardless of Ig mutation status (0.47). Telomere length differed significantly between GC-like (0.73) and non-GC-like DLBCLs (0.43), and follicular lymphomas (FLs) had shorter telomeres (0.53) than GC-DLBCL. Hairy cell leukemias, which display Ig gene intraclonal heterogeneity, had longer telomeres (0.62) than FLs and non-GC-DLBCL, but shorter than GC-DLBCL. We conclude that although DLBCL and CLL subsets can be clearly distinguished, telomere length reflects many parameters and may not simply correlate with GC-related origin.
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| 15. |
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| 16. |
- Chang, Ellen T., et al.
(författare)
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Family history of hematopoietic malignancy and risk of lymphoma
- 2005
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 97:19, s. 1466-1474
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: A family history of hematopoietic malignancy is associated with an increased risk of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL), although the magnitude of the relative risk is unclear. We estimated the association between familial hematopoietic cancer and risk of lymphoma using validated, registry-based family data, and we also investigated whether associations between some environmental exposures and risk of lymphoma vary between individuals with and without such a family history. METHODS: In a population-based case-control study of malignant lymphoma, 1506 case patients and 1229 control subjects were linked to the Swedish Multi-Generation Register and then to the Swedish Cancer Register to ascertain history of cancer in first-degree relatives of patients with malignant lymphoma. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with the risk of lymphoma. RESULTS: A history of hematopoietic malignancy in any first-degree relative was associated with an increased risk of all NHL (OR = 1.8, 95% CI = 1.2 to 2.5), common B-cell NHL subtypes, and HL. Relative risks were generally stronger in association with sibling hematopoietic cancer (OR for all NHL = 3.2, 95% CI = 1.3 to 7.6) than with parental hematopoietic cancer (OR = 1.6, 95% CI = 1.1 to 2.3). A family history of NHL or chronic lymphocytic leukemia (CLL) was associated with an increased risk of several NHL subtypes and HL, whereas familial multiple myeloma was associated with a higher risk of follicular lymphoma. There was no statistically significant heterogeneity in NHL risk associations with environmental factors between individuals with and without familial hematopoietic malignancy. CONCLUSIONS: The increased risk of NHL and HL among individuals with a family history of hematopoietic malignancy was approximately twofold for both lymphoma types. There was no evidence that etiologic associations varied between familial NHL and nonfamilial NHL.
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| 17. |
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| 18. |
- Jönbrink, Anna Karin, et al.
(författare)
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Create Competitiveness In A Sustainable Society : - Use Ecodesign, In Cooperation
- 2011
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Ingår i: Design for Innovative Value Towards a Sustainable Society. - Dordrecht : Springer Science+Business Media B.V.. ; , s. 430-433
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Konferensbidrag (refereegranskat)abstract
- This paper will describe a new methodology for the use of Ecodesign, where various competences are combined to obtain high quality results. The competences needed are: Environmental experts, who can evaluate the environmental performance of a product or service through Life Cycle Assessment, LCA, material- and process experts for the materials and processes in the targeted product or service, experts of the final product or service who can provide high quality data for the LCA. This cross functional team can develop new products or services, with high performance combined with low environmental impact, applying ecodesign when cooperating closely. Using this methodology is a feasible way to obtain improved competitiveness for the industry in a sustainable society.
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| 19. |
- Kaderi, Mohd Arifin, et al.
(författare)
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The GNAS1 T393C polymorphism and lack of clinical prognostic value in chronic lymphocytic leukemia
- 2008
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 32:6, s. 984-987
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease with no known single predisposing genetic factor shown in all cases. Recently, a single nucleotide polymorphism (SNP) T393C in the GNAS1 gene has been reported to have a clinical impact on CLL progression and overall survival. In order to further investigate the T393C SNP in CLL, we have genotyped 279 CLL cases and correlated the genotypes to clinical outcome and other known prognostic factors such as the immunoglobulin heavy chain variable (IGHV) gene mutation status and CD38 expression. In the present study, no difference in overall survival or time to treatment was observed in the CLL patients with the different genotypes in contrast to the previous report. Furthermore, no correlation was observed with the T393C genotypes and IGHV mutational status, Binet stage or CD38 in this cohort. In summary, our data does not support the use of the T393C GNAS SNP as a clinical prognostic factor in CLL.
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| 20. |
- Lovvik, T. S., et al.
(författare)
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Pregnancy and perinatal outcomes in women with polycystic ovary syndrome and twin births : a population-based cohort study
- 2015
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Ingår i: British Journal of Obstetrics and Gynecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 122:10, s. 1295-1302
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To investigate pregnancy and perinatal outcomes in twin births among women with and without polycystic ovary syndrome (PCOS) diagnosis. Design: Population-based cohort study. Setting: Sweden. Population: We identified 20965 women with twin births between 1995 and 2009 of whom 226 had a PCOS diagnosis through linkage between the Swedish Medical Birth Register and the Swedish National Patient Register. Methods: Calculating risk ratios (RR) with 95% confidence intervals (CI) using a log-binomial regression model and hazard ratios (HR) with 95% CI for preterm birth. Main outcome measures: Preterm birth, low birthweight, caesarean section, pre-eclampsia, Apgar score <7 at 5minutes and perinatal mortality. Results: PCOS diagnosis in twin pregnancy was associated with increased risk of preterm delivery (51% versus 43%, RR 1.18 [95% CI 1.03-1.37]), particularly spontaneous preterm delivery (37% versus 28%; RR 1.30 [95% CI 1.09-1.55]) and very preterm birth (<32weeks) (14% versus 8%, RR 1.62 [95% CI 1.10-2.37]). Twins of PCOS mothers had more often low birthweight (48% versus 39%, adjusted RR 1.40 [95% CI 1.09-1.80]). This difference disappeared when adjusting for gestational age. No risk difference was found for caesarean section, pre-eclampsia, low 5-minute Apgar score or perinatal mortality. Conclusions: The risk of preterm delivery in twin pregnancies is increased by having a PCOS diagnosis. This should be considered in risk estimation and antenatal follow-up of twin pregnancies.
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| 21. |
- Roos, Anna-Karin
(författare)
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Delivery of DNA vaccines against cancer
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- DNA vaccines against cancer have shown promising results in animal models. Efficient antigenspecific T cell responses and tumor protection have been demonstrated after vaccination with DNA encoding tumor antigens in mice. Phase I clinical trials have furthermore demonstrated that repetitive DNA vaccinations in humans are well tolerated, and that tumor antigen-specific immune responses can be induced. However, it stands clear that new adjuvants and/or delivery systems need to be explored to enhance the anti-tumor immune responses activated by DNA vaccines in humans. The aim of the studies in this thesis was to investigate different adjuvants and delivery methods for a DNA vaccine against prostate cancer (PC). PC is the most commonly diagnosed cancer in Swedish men (~ 9000 new cases/year), and the fourth leading cause of cancer-related deaths in the developed countries worldwide. Current treatments are debilitating and only available for localized disease. For men with hormone-refractory PC there is no curative treatment and the prognosis is extremely poor. Therefore, there is an urgent need for new treatment strategies. The development of immunotherapeutic vaccination protocols against PC, based on the induction of autoimmunity to prostate tissues, is attractive since the prostate is not a vital organ beyond the reproductive years. The DNA vaccine used in these studies encodes prostate-specific antigen (PSA), a protein expressed almost exclusively by normal prostate epithelial cells and PC cells. The first study of our PSA/DNA vaccine demonstrated that PSA-specific cytotoxic T lymphocytes could be induced in mice. When two cytokine adjuvants, granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-2 (IL-2), were co-delivered with the DNA vaccine, 80 % of the mice were protected against a syngenic challenge with PSA-expressing tumor cells. Next the safety, feasibility, and biological efficacy of the PSA/DNA vaccine was evaluated in a phase I clinical trial in patients with hormone-refractory PC. The DNA vaccine was delivered in doses of 100, 300 or 900 ìg together with the cytokines GM-CSF and IL-2, during five cycles with monthly intervals. No adverse effects (WHO grade >2) were observed in any patients. PSA-specific cellular responses and an increase in anti-PSA antibodies were detected in two of three patients after vaccination with the highest vaccine dose. This proved an important proof of principle, namely that tolerance to PSA in PC patients could be overcome by vaccination with PSA/DNA. The clinical study furthermore made clear that DNA vaccination must induce more effective immune responses to have an impact on survival of PC patients. To further improve PSA-specific immune responses induced by the PSA/DNA vaccine we investigated a new delivery method, in vivo electroporation (EP). When injecting the DNA vaccine intradermally and applying a short sequence (~ 3 sec) of optimized electrical pulses, the number of induced PSA-specific CD8+ T cells was greatly increased. The amount of DNA necessary to induce PSA-specific T cells could be reduced by 80 % when the DNA was delivered intradermally with EP, compared to nonelectroporative delivery in muscle. In preparation for a second clinical trial, where a xenogenic DNA vaccine encoding rhesus PSA will be delivered intradermally in combination with EP, an amino acid substitution in rhesus PSA creating a naturally processed and presented epitope with high HLA affinity was identified. As PSA/DNA encoding this modified epitope induces PSAspecific T cells in all human and murine T cell cultures tested, we believe that this epitope will facilitate the monitoring of vaccine efficacy in PSA/DNA vaccinated cancer patients.
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| 22. |
- Roos, Karin, et al.
(författare)
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Circulating anti-citrullinated protein antibodies containing secretory component are prognostic for arthritis onset in at-risk patients
- 2021
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Ingår i: Clinical and Experimental Immunology. - : Wiley. - 0009-9104 .- 1365-2249. ; 204:3, s. 344-351
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Tidskriftsartikel (refereegranskat)abstract
- Autoantibodies related to rheumatoid arthritis (RA), such as anti-citrullinated protein antibodies (ACPA), are often detectable in the preclinical period years before arthritis onset. However, events triggering arthritis development remain incompletely known. We aimed to determine whether ACPA isotype levels are prognostic for arthritis development in patients presenting with immunoglobulin (Ig)G ACPA and musculoskeletal pain. Study participants (n = 82) had musculoskeletal pain of any sort and duration and a positive IgG ACPA test. None of the patients had arthritis upon clinical examination at baseline, but during follow-up (mean = 6 years), 48% developed at least one arthritic joint. IgG, IgA, IgM and secretory component (SC)-containing ACPA was measured in longitudinally collected serum samples. Cox regression analysis was performed to test the prognostic value of baseline antibody levels and changes over time. All analysed ACPA isotype levels were associated with arthritis development in univariable Cox regression analysis. In multivariable analysis, baseline SC ACPA levels were independently prognostic for arthritis development in multivariable analysis [hazard ratio (HR) = 1 center dot 006, 95% confidence interval (CI) = 1 center dot 001-1 center dot 010, P = 0 center dot 012]. There were no significant changes in ACPA isotype levels over time, and no significant association between changes over time and arthritis development. In this prospective longitudinal study, baseline serum SC ACPA levels, but neither IgG, IgA nor IgM ACPA are prognostic for future arthritis development. Repeated measurement of ACPA isotypes do not bring additional prognostic value. The results reinforce a mucosal connection in RA development and encourage further exploration of the mechanisms underlying secretory ACPA formation as a trigger for arthritis development.
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| 23. |
- Roos, Karin, et al.
(författare)
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Circulating secretory IgA antibodies against cyclic citrullinated peptides in early rheumatoid arthritis associate with inflammatory activity and smoking
- 2016
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Ingår i: Arthritis Research & Therapy. - : BIOMED CENTRAL LTD. - 1478-6362. ; 18:119
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Tidskriftsartikel (refereegranskat)abstract
- Background: A possible association between mucosal immunization and inflammation, as well as the initiation and propagation of rheumatoid arthritis (RA), is attracting renewed interest. The aim of this study was to evaluate the possible occurrence and clinical correlations of circulating secretory immunoglobulin A (SIgA) antibodies against the second-generation cyclic citrullinated peptides (CCP) among patients with recent-onset RA followed prospectively over 3 years. Methods: Baseline serum samples from 636 patients with recent-onset RA were analyzed for SIgA anti-CCP antibodies by using an enzyme-linked immunosorbent assay with a secondary antibody directed against secretory component. SIgA anti-CCP status at baseline was analyzed in relation to smoking, HLA-DRB1/shared epitope (SE), and the disease course over 3 years. Significant findings were evaluated in regression analysis that included age, sex, smoking, and SE. Results: Seventeen percent of the patients tested positive for circulating SIgA anti-CCP, and the occurrence was confirmed by detection of secretory component in an affinity-purified IgA anti-CCP fraction. SIgA anti-CCP positivity at baseline was associated with slightly higher baseline erythrocyte sedimentation rate (ESR) (mean 38 vs. 31 mm/first hour, p = 0.004) and C-reactive protein (CRP) (mean 30 vs. 23 mg/L, p = 0.047). During follow-up, SIgA anti-CCP-positive patients had a higher mean AUC regarding ESR (adjusted p = 0.003), although there were no significant differences regarding CRP, tender and swollen joint counts, or radiological joint damage (median Larsen progression 1.0 vs. 1.0, p = 0.22). SIgA anti-CCP was associated significantly with smoking (79 % ever smokers among SIgA anti-CCP-positive patients vs. 59 % in SIgA anti-CCP-negative patients, adjusted OR 2.19, 95 % CI 1.01-4.37, p = 0.027) but not with carriage of the SE (80 % vs. 73 %, p = 0.62). Conclusions: Circulating SIgA anti-CCP, which is present in a subgroup of patients with early RA, is not related to SE, but it is environmentally linked to cigarette smoking. This finding strengthens the hypothesis that immunization against citrullinated peptides and/or proteins may occur at mucosal surfaces of the airways. Analysis of SIgA antibodies in serum may be a convenient and more versatile means to investigate the "mucosal connection" in RA compared with analyses in mucosal fluid samples.
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| 24. |
- Roos Ljungberg, Karin, et al.
(författare)
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Presence of salivary IgA anti-citrullinated protein antibodies associate with higher disease activity in patients with rheumatoid arthritis
- 2020
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Ingår i: Arthritis Research & Therapy. - : BMC. - 1478-6362. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Circulating IgA anti-citrullinated protein antibodies (ACPA) associate with more active disease, but a previous study implied that salivary IgA ACPA is related to a less severe disease. Therefore, we aimed to characterize the IgA ACPA response in the saliva and serum in relation to clinical picture and risk factors among patients with rheumatoid arthritis (RA).Methods: RA patients (n=196) and healthy blood donors (n=101), included in the cross-sectional study "Secretory ACPA in Rheumatoid Arthritis" (SARA), were analyzed for ACPA of IgA isotype, and for subclasses IgA1 and IgA2 ACPA in paired saliva and serum samples using modified enzyme-linked immunosorbent assays (ELISA) targeting reactivity to a cyclic citrullinated peptide (anti-CCP). Cutoff levels for positive tests were set at the 99th percentile for blood donors. Antibody levels were related to clinical characteristics, radiographic damage, smoking habits, and carriage of HLA-DRB1/shared epitope (SE).Results: IgA ACPA in the saliva was found in 12% of RA patients, IgA1 occurred in 10%, and IgA2 in 9%. In serum, IgA ACPA was found in 45% of the patients, IgA1 in 44%, and IgA2 in 39%. Levels of IgA ACPA in the saliva correlated significantly with serum levels of IgA (r=0.455). The presence of salivary IgA ACPA was associated with a higher erythrocyte sedimentation rate (ESR), 28-joint disease activity score, tender joint count, and patient global assessment at the time of sampling. None of the antibodies was associated with smoking, SE, or radiographic damage.Conclusion: Salivary IgA ACPAs were detected in a subset of RA patients in association with higher disease activity. This suggests that mucosal ACPA responses in the oral cavity may contribute to disease-promoting processes in RA.
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| 25. |
- Roos Ljungberg, Karin, et al.
(författare)
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Secretory anti-citrullinated protein antibodies in serum associate with lung involvement in early rheumatoid arthritis
- 2020
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 59:4, s. 852-859
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Tidskriftsartikel (refereegranskat)abstract
- Objective. A 'mucosal connection' in RA presently attracts increasing attention. We recently described the occurrence of secretory antibodies to citrullinated protein (SC-ACPA) in sera from patients with recent-onset RA. The current study was performed to evaluate possible associations between serum levels of secretory ACPA and signs of lung involvement in patients with early, untreated RA. Methods. One hundred and forty-two RA patients were included as part of the 'LUng Investigation in newly diagnosed RA' study. One hundred and six patients were examined with high-resolution CT (HRCT) and 20 patients underwent bronchoscopy, where bronchial biopsies and bronchoalveolar lavage fluid (BALF) samples were obtained. SC-ACPA in serum and BALF were detected by an enzyme-linked immunoassay. Antibody levels were related to smoking history, pulmonary function, HRCT, BALF cell counts and findings in bronchial biopsies. Results. SC-ACPA occurred in 16% of the serum samples and in 35% of the BALF samples. SC-ACPA levels in serum correlated with SC-ACPA levels in BALF (sigma = 0.50, P = 0.027) and were higher among patients with HRCT parenchymal lung abnormalities (P = 0.022) or bronchiectasis (P = 0.042). Also, ever smoking was more frequent among serum SC-ACPA-positive patients (91% vs 67%, P = 0.023), and the SC-ACPA levels correlated with the number of pack-years (sigma=0.20, P = 0.020). Conclusion. In early, untreated RA, serum levels of SC-ACPA reflect lung involvement in terms of local ACPA levels, smoking and lung abnormalities on HRCT. These findings strengthen the link between mucosal ACPA responses and the lungs in RA.
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| 26. |
- Roos Ljungberg, Karin, 1988-
(författare)
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Secretory Autoantibodies in Rheumatoid Arthritis
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease in which autoantibodies, such as anti-citrullinated protein antibodies (ACPA), can be detected in the serum of patients. Autoantibodies may appear in the circulation years before clinical signs of joint inflammation occur, indicating that early immunological pathogenetic steps take place outside of the joints. Although many of these mechanisms are currently unknown, the initial events leading up to ACPA production are thought to occur at mucosal surfaces. In this thesis, mucosa-associated secretory ACPA are investigated in the circulation and in local mucosal secretions to: (i) improve the understanding of the mucosal connection in RA; and (ii) investigate whether these antibodies can improve diagnostics and prognostics in early RA. We identified circulating secretory component containing (SC) ACPA in a subpopulation of patients (both early and established RA) and at-risk patients, with a prevalence of 16%-21%. In addition, SC ACPA was detected in bronchoalveolar lavage fluid (BALF) and IgA ACPA in saliva, indicating local production in the lungs and in the oral cavity. In at-risk patients who were positive for IgG ACPA, we found that the levels of circulating SC ACPA at inclusion predicted arthritis development. Circulating SC ACPA was associated with higher disease activity, including increased levels of inflammatory markers, in patients with early RA. Levels of circulating SC ACPA were associated with high-resolution computed tomography (HRCT) findings (parenchymal lung abnormalities and bronchiectasis) and smoking, but not with risk genes (shared epitope). We confirmed the presence of salivary ACPA and identified a novel association with increased disease activity and functional disability. In summary, SC ACPA is present in the sera of patients with RA who manifest different phases of the disease, and we found associations with arthritis onset, smoking, systemic inflammation, and lung abnormalities. SC ACPA is also detectable in mucosal secretions from the lungs and the oral cavity. These findings suggest that mucosal ACPA production may be an important factor in RA development and progression, and that serum SC ACPA should be further evaluated as a prognostic marker for disease onset among at-risk individuals.
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| 27. |
- Schrijver, Lieske H, et al.
(författare)
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Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers : an international cohort study
- 2021
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 225:1, s. 1-51
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive preparations (OCPs) use. While the effects of OCPs in the general population are well established (∼50% reduction), the estimated risk reduction in mutation carriers is much less precise due to potential bias and small sample sizes. In addition, only a few studies have examined the associations between duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer.OBJECTIVE(S): To investigate in more detail the associations between various characteristics of OCP use and risk of ovarian cancer, to provide health care providers and carriers with better risk estimates.STUDY DESIGN: In this international retrospective study, ovarian cancer risk associations were assessed using OCP data on 3,989 BRCA1 and 2,445 BRCA2 mutation carriers. Age-dependent weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as covariate. To minimize survival bias, analyses were left-truncated at 5 years before baseline questionnaire. Separate analysis were conducted for each of the aspects of OCP use and in a multivariate analysis including all these aspects. In addition, the analysis of duration of OCP use was stratified by recency of use.RESULTS: OCPs were less often used by mutation carriers who were diagnosed with ovarian cancer (Ever use: BRCA1 58.6%, BRCA2 53.5%) than by unaffected carriers (Ever use: BRCA1 88.9%, BRCA2 80.7%. The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer, and 9 and 8 years for ovarian cancer unaffected BRCA1 and BRCA2 carriers, respectively. For BRCA1 mutation carriers univariate analyses showed that both a longer duration of OCP use and more recent use of OCPs were inversely associated with risk of ovarian cancer. However, in multivariate analyses including duration of use, age at first use and time since last use, duration of use proved to be the prominent protective factor (compared with <5 years, 5-9 years HR=0.67;95%CI 0.40-1.12, 10+ years HR=0.37;95%CI 0.19-0.73; ptrend=0.008). The inverse association between duration of use and ovarian cancer risk persisted for more than 15 years (Duration of ≥10 years; BRCA1: <15 years since last use: HR=0.24 95%CI 0.14-0.43, 15+ years since last use: HR 0.56 95%CI 0.18-0.59). Univariate results for BRCA2 mutation carriers were similar, but due to limit sample size inconclusive.CONCLUSION: For BRCA1 mutation carriers, a longer duration of OCP use is associated with a greater reduction of ovarian cancer risk and the protection is long term.
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| 28. |
- Schöllkopf, Claudia, et al.
(författare)
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Cigarette smoking and risk of non-Hodgkin's lymphoma : a population-based case-control study
- 2005
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 14:7, s. 1791-1796
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epidemiologic evidence of an association between tobacco smoking and non-Hodgkin's lymphoma has been conflicting. This may reflect that non-Hodgkin's lymphoma comprises several distinct disease entities with different etiologies, as some studies have indicated an association between smoking and follicular lymphoma. OBJECTIVE: To investigate the association between cigarette smoking and non-Hodgkin's lymphoma risk, overall and by subtype. METHODS: As part of a nationwide Danish-Swedish population-based case-control study, we interviewed 3,055 incident non-Hodgkin's lymphoma patients and 3,187 population controls. All lymphomas were uniformly classified according to the WHO classification. We used unconditional logistic regression to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for the association between cigarette smoking and risk of non-Hodgkin's lymphoma. RESULTS: Cigarette smoking was not associated with the risk of non-Hodgkin's lymphoma overall (OR, 0.97; 95% CI, 0.87-1.08) nor with the major subgroups such as diffuse large B-cell lymphoma (OR, 0.94; 95% CI, 0.79-1.10), chronic lymphocytic leukemia (OR, 0.86; 95% CI, 0.72-1.02), or follicular lymphoma (OR, 1.03; 95% CI, 0.85-1.24). Female smokers were at a marginally increased risk of follicular lymphoma (OR, 1.41; 95% CI, 1.04-1.92). Men who had ever smoked had a significantly increased risk of T-cell lymphoma (OR, 1.67; 95% CI, 1.11-2.51). No dose-response association with cigarette smoking could be established for any lymphoma subgroup. CONCLUSION: We found little evidence of an association between cigarette smoking and non-Hodgkin's lymphoma risk overall. Although increased risks of follicular lymphoma in female smokers and of T-cell lymphoma in male smokers were suggested, no dose-response relationship was observed, leaving limited support for causality.
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| 29. |
- Sonne, C., et al.
(författare)
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Health effects from contaminant exposure in Baltic Sea birds and marine mammals: A review
- 2020
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 139
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Tidskriftsartikel (refereegranskat)abstract
- Here we review contaminant exposure and related health effects in six selected Baltic key species. Sentinel species included are common eider, white-tailed eagle, harbour porpoise, harbour seal, ringed seal and grey seal. The review represents the first attempt of summarizing available information and baseline data for these biomonitoring key species exposed to industrial hazardous substances focusing on anthropogenic persistent organic pollutants (POPs). There was only limited information available for white-tailed eagles and common eider while extensive information exist on POP exposure and health effects in the four marine mammal species. Here we report organ-tissue endpoints (pathologies) and multiple biomarkers used to evaluate health and exposure of key species to POPs, respectively, over the past several decades during which episodes of significant population declines have been reported. Our review shows that POP exposure affects the reproductive system and survival through immune suppression and endocrine disruption, which have led to population-level effects on seals and white-tailed eagles in the Baltic. It is notable that many legacy contaminants, which have been banned for decades, still appear to affect Baltic wildlife. With respect to common eiders, changes in food composition, quality and contaminant exposure seem to have population effects which need to be investigated further, especially during the incubation period where the birds fast. Since new industrial contaminants continuously leak into the environment, we recommend continued monitoring of them in sentinel species in the Baltic, identifying possible effects linked to climate change, and modelling of population level effects of contaminants and climate change. © 2020 The Authors
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| 30. |
- Svard, Anna, et al.
(författare)
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Secretory antibodies to citrullinated peptides in plasma and saliva from rheumatoid arthritis patients and their unaffected family members
- 2019
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 78, s. 1097-1097
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background Mucosal involvement in early phases of rheumatoid arthritis (RA) pathophysiology has emerged as an attractive hypothesis, supported by several findings. Elevated levels of antibodies against citrullinated peptides/proteins (ACPA) can be found during a long pre-symptomatic period, preceding manifest arthritis. Secretory antibodies are produced at mucosal surfaces, but can also be detected in the circulation. Secretory ACPA in plasma has been demonstrated in patients with RA (1). First-degree relatives (FDRs) of patients with RA can be regarded as potential pre-RA patients or at-risk individuals. In a previous study, a higher prevalence of ACPA was found in FDRs than in healthy controls (2), with IgA-ACPA being more common than IgG-ACPA.We hypothesized that formation of secretory ACPA is an early step in RA development, preceding the occurrence of regular non-secretory ACPA, and consequently secretory ACPA would be prevalent in a large proportion of FDRs.Objectives To evaluate secretory ACPA in plasma and saliva from patients with RA and FDRs.Methods We analyzed secretory antibodies to 2nd generation cyclic citrullinated peptides (anti-CCP) in plasma from 194 patients with RA and 191 FDRs unaffected by RA and salivary samples from 25 RA patients, 21 first-degree relatives and 11 controls.In plasma, cutoff for secretory ACPA was set at the 99th percentile of healthy blood donors. In saliva, a positive test was defined as a difference between optical density values for IgA anti-CCP and IgA anti-cyclic arginine peptide (delta OD value) >2 SD above the mean delta OD value of the controls.Mann-Whitney U test was used for continuous variables and Pearson Chi-square for categorical variables.Results Secretory ACPA occurred in 37 (19.1%) of RA patients but only in 2 (1%) of FDRs (table 1). Salivary IgA ACPA was found in 3/25 (12%) of patients with RA, but not in any of the 21 FDRs. 27% of FDRs were positive for regular non-secretory IgA ACPA in plasma, and out of them, only 2 individuals (5%) were positive for secretory ACPA in plasma. Among FDRs negative for regular ACPAs, no one was positive for secretory ACPA. Secretory ACPA had the highest PPV for identifying patients, while IgG ACPA had the highest negative predictive value (table 2).
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| 31. |
- Svärd, Anna, et al.
(författare)
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Antibodies against Porphyromonas gingivalis in serum and saliva and their association with rheumatoid arthritis and periodontitis. : Data from two rheumatoid arthritis cohorts in Sweden
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Periodontitis and oral pathogenic bacteria can contribute to the development of rheumatoid arthritis (RA). A connection between serum antibodies to Porphyromonas gingivalis (P. gingivalis) and RA has been established, but data on saliva antibodies to P. gingivalis in RA are lacking. We evaluated antibodies to P. gingivalis in serum and saliva in two Swedish RA studies as well as their association with RA, periodontitis, antibodies to citrullinated proteins (ACPA), and RA disease activity.Methods: The SARA (secretory antibodies in RA) study includes 196 patients with RA and 101 healthy controls. The Karlskrona RA study includes 132 patients with RA >= 61 years of age, who underwent dental examination. Serum Immunoglobulin G (IgG) and Immunoglobulin A (IgA) antibodies and saliva IgA antibodies to the P. gingivalis-specific Arg-specific gingipain B (RgpB) were measured in patients with RA and controls.Results: The level of saliva IgA anti-RgpB antibodies was significantly higher among patients with RA than among healthy controls in multivariate analysis adjusted for age, gender, smoking, and IgG ACPA (p = 0.022). Saliva IgA anti-RgpB antibodies were associated with RA disease activity in multivariate analysis (p = 0.036). Anti-RgpB antibodies were not associated with periodontitis or serum IgG ACPA.Conclusion: Patients with RA had higher levels of saliva IgA anti-RgpB antibodies than healthy controls. Saliva IgA anti-RgpB antibodies may be associated with RA disease activity but were not associated with periodontitis or serum IgG ACPA. Our results indicate a local production of IgA anti-RgpB in the salivary glands that is not accompanied by systemic antibody production.
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| 32. |
- Svärd, Anna, et al.
(författare)
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Secretory antibodies to citrullinated peptides in plasma and saliva from rheumatoid arthritis patients and their unaffected first-degree relatives
- 2020
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Ingår i: Clinical and Experimental Immunology. - : WILEY. - 0009-9104 .- 1365-2249. ; 199:2, s. 143-149
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate secretory antibodies to citrullinated proteins (ACPA) in plasma and immunoglobulin (Ig)A ACPA in saliva from patients with rheumatoid arthritis (RA) and their unaffected first-degree relatives (FDRs). Patients with RA (n = 194) and first-degree relatives unaffected by RA (n = 191) were recruited for analysis of secretory antibodies to second-generation cyclic citrullinated peptides (anti-CCP) in plasma. From a subpopulation (25 RA patients, 21 first-degree relatives and 11 controls), saliva samples were obtained for IgA anti-CCP analysis. The presence of secretory ACPA was compared between subject categories, and related to genetic and environmental risk factors. Secretory ACPA occurred in 37 (19%) plasma samples from patients with RA, but only in two (1%) of FDRs. IgA ACPA in saliva was found in three of 25 (12%) patients with RA, but not in any of the 21 FDRs (< 5%). No significant associations were seen between the presence of secretory ACPA and SE or smoking, either among RA patients or among FDRs. Despite occurring in 19% of RA plasma, secretory ACPA was rare in both saliva and plasma among FDRs, even among those positive for conventional ACPA of non-mucosal origin. Longitudinal studies are warranted to determine whether circulating secretory ACPA occurs before or in parallel with the development of clinical arthritis.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Tobin, Gerard, et al.
(författare)
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Subsets with restricted immunoglobulin gene rearrangement features indicate a role for antigen selection in the development of chronic lymphocytic leukemia.
- 2004
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 104:9, s. 2879-85
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Tidskriftsartikel (refereegranskat)abstract
- Pseudohypoaldosteronism type I (PHA1) is a condition associated with salt wasting leading to dehydration, hypotension, hyperkalemia, and metabolic acidosis. Sporadic cases and two familial forms, one autosomal dominant and one autosomal recessive form, have been described. The autosomal dominant or sporadic form manifests milder salt wasting that remits with age. Mutations in the gene encoding the mineralocorticoid receptor (MR) have been identified in patients with the autosomal dominant inheritance. However, recent studies suggest that the autosomal dominant and sporadic forms are genetically heterogeneous and that additional genes might be involved. We report on the study of 15 members of a Swedish five-generation family with the autosomal dominant form of PHA1. Interestingly, neuropathy was found in two of five affected individuals. A novel heterozygous nonsense mutation C436X in exon 2 was identified in the index patient by linkage analysis, PCR, and direct sequencing of the MR gene. Analysis of the family demonstrated that the mutation segregated with PHA1 in the family. It is unclear whether the neuropathy is associated with the mutation found. Our results together with previously published data suggest that loss-of-function mutations of the MR gene located at 4q31.1, commonly are associated with the autosomal dominant form of PHA1.
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| 38. |
- Valgeirsdóttir, Heiddis, et al.
(författare)
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Polycystic ovary syndrome and extremely preterm birth : A nationwide register-based study
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:2
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Women with polycystic ovary syndrome (PCOS) have increased risk of pregnancy complications, including preterm birth before 37 weeks. However, if this increased risk also includes extremely preterm births (<28 weeks) is unknown. Such information is important to identify women at risk and tailor antenatal care, since child morbidity and mortality become more prevalent with increasing prematurity.AIMS: To investigate the association between PCOS and extremely preterm birth, and whether onset of PCOS-related preterm birth is predominantly spontaneous or medically indicated.MATERIAL AND METHODS: This was a nationwide register-based cohort study in Sweden. The study population was all live singleton births registered in the Swedish Medical Birth Register 2005-2014 (n = 1 046 448). Women with and without PCOS were compared by severity of preterm birth [extremely (22+0 to 27+6 weeks), very (28+0 to 31+6 weeks) and moderately (32+0 to 36+6 weeks)] and delivery onset mode (spontaneous or medically indicated). Multinomial logistic regression was performed to estimate adjusted odds ratios (aOR) with 95% confidence intervals (CI). Adjustments were made for maternal age, parity, body mass index, smoking, country of birth and year of delivery.RESULTS: During the study period, 1.3% of the women giving birth had PCOS diagnosis. They had an overall higher preterm birth rate than women without PCOS (6.7% and 4.8%, respectively). Women with PCOS had increased odds of preterm birth of all severities, with the highest odds for extremely preterm birth (aOR 2.3; 95% CI 1.7-3.0), particularly of spontaneous onset (aOR 2.7; 95% CI 2.0-3.6).CONCLUSIONS: Women with PCOS had more than a two-fold increased risk of extremely preterm birth with spontaneous onset than women without such diagnosis. This can be important in antenatal risk assessment of preterm birth in women with PCOS. Future research is warranted to investigate the biological mechanisms behind preterm birth in women with PCOS.
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| 39. |
- Valgeirsdóttir, Heiddis, et al.
(författare)
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Polycystic ovary syndrome and risk of stillbirth : A nationwide register-based study
- 2021
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Ingår i: British Journal of Obstetrics and Gynecology. - : John Wiley & Sons. - 1470-0328 .- 1471-0528. ; 128:13, s. 2073-2082
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo investigate whether polycystic ovary syndrome (PCOS) is associated with increased risk of stillbirth and whether any such association is linked to PCOS with a severe hyperandrogenic profile.DesignNationwide register-based cohort study.SettingSweden.PopulationThe cohort consisted of women giving birth to singleton infants in 1997–2015. All women with a diagnosis of PCOS in the period 1997–2017 and a randomly selected reference group of women without PCOS diagnosis were included. PCOS with a severe hyperandrogenic profile was defined as a PCOS diagnosis with at least two dispensations of prescribed anti-androgens during 2005–2017.MethodsThe risk of stillbirth in women with PCOS was estimated through multiple logistic regression, using women without PCOS as a reference. Risks were expressed as adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs), adjusted for maternal age, parity, body mass index, type-1 diabetes, educational level and country of birth.Main outcome measuresStillbirth, at ≥22 weeks of gestation in 2008–2015 and at ≥28 weeks of gestation in 1997–2007.ResultsCompared with women without PCOS (n = 241 750), women with PCOS (n = 41 851) had a 50% increased risk of stillbirth (aOR 1.50, 95% CI 1.28–1.77). The incidence of stillbirth in women with PCOS was particularly increased at term. Women with PCOS and a severe hyperandrogenic profile (n = 13 713) did not have a stronger association with stillbirth than women with PCOS who did not have such a profile.ConclusionsPCOS is associated with stillbirth and should be considered as a possible risk factor in antenatal care. Further research is warranted to investigate possible causal mechanisms.
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| 40. |
- Valgeirsdóttir, Heiddis, et al.
(författare)
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Prenatal exposures and birth indices, and subsequent risk of polycystic ovary syndrome : a national registry-based cohort study
- 2019
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Ingår i: British Journal of Obstetrics and Gynecology. - : WILEY. - 1470-0328 .- 1471-0528. ; 126:2, s. 244-251
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study the associations between prenatal exposures and risk of developing polycystic ovary syndrome (PCOS).Design: National registry-based cohort study.Setting: Sweden.Population: Girls born in Sweden during the years 1982-1995 (n = 681 123).Methods: The girls were followed until the year 2010 for a diagnosis of PCOS. We estimated the associations between maternal body mass index (BMI), smoking, and size at birth with the risk of developing a PCOS diagnosis. Risks were calculated by adjusted hazard ratio (aHR) and 95% confidence intervals (95% CIs). Main outcome measures A diagnosis of PCOS at 15 years of age or later.Results: During the follow-up period 3738 girls were diagnosed with PCOS (0.54%). Girls with mothers who were overweight or obese had 1.5-2.0 times higher risk of PCOS (aHR 1.52, 95% CI 1.36-1.70; aHR 1.97, 95% CI 1.61-2.41, respectively), compared with girls born to mothers of normal weight. The risk of PCOS was increased if the mother smoked during pregnancy (1-9 cigarettes/day, aHR 1.31, 95% CI 1.18-1.47; >= 10 cigarettes/day, aHR 1.44, 95% CI 1.27-1.64). Being born small for gestational age (SGA) was associated with a later diagnosis of PCOS in crude estimates, but the association was not significant after adjusting for maternal factors.Conclusions: Maternal smoking and increased BMI appear to increase the risk of PCOS in offspring. The association between SGA and the development of PCOS appears to be mediated by maternal factors.
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| 41. |
- Wiberg, Karin, et al.
(författare)
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Concentrations and enantiomer fractions of organochlorine compounds in Baltic species hit by reproductive impairment
- 2002
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 21:12, s. 2542-2551
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Tidskriftsartikel (refereegranskat)abstract
- Concentrations and enantiomer fractions (EFs) of organochlorine compounds (OCs) were determined in tissues of gray seal (Halichoerus grypus) and salmon (Salmo salar) originating from the Baltic Sea. The selected seal specimens ranged from starved to unstarved animals, and some of them suffered from a disease complex, while the salmon samples originated from individuals, which were known to produce offspring with and without the M74 syndrome. Significant differences in residue levels and EFs were found between seal groups but not between M74 salmon and non-M74 salmon. The relations between chemical and biological variables of seal samples were investigated with multivariate statistics. Poor health status correlated strongly with age, while bad nutrition condition was associated mainly with high pollution loads and distinctively nonracemic chiral OC compositions. High biotransformation rate (as indicated by fraction of chlordane metabolites in relation to total level of chlordanes) was also associated with large deviations from racemic values and high contaminant levels.
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| 42. |
- Wilhelmsson, Anna, et al.
(författare)
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Motivation to uphold physical activity in women with breast cancer during adjuvant chemotherapy treatment
- 2017
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Ingår i: European Journal of Oncology Nursing. - : Elsevier. - 1462-3889 .- 1532-2122. ; 29, s. 17-22
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Physical activity (PA) is important for recovery after a breast cancer diagnosis; however, women's motivation to engage in PA can be impacted by disease and/or treatment, and can therefore be a challenge. This study explored factors associated with PA levels during chemotherapy among women with breast cancer.METHOD: The study had a cross-sectional descriptive and comparative design using a study-specific questionnaire. One hundred women with breast cancer receiving adjuvant chemotherapy were included. Data were analysed by Pearson's correlation coefficient and linear regression. The open question was subjected to manifest content analysis.RESULTS: Identified factors associated with engaging in PA during chemotherapy treatment were: being physically active before diagnosis, and the information given by the oncology nurse before the treatment start. The physically active women experienced higher psychological wellbeing, less fatigue, and faster recovery after treatment. They also experienced an overall feeling of fitness.CONCLUSION: It seems that PA is associated with less fatigue, better recovery between chemotherapy treatments, and a better mental condition leading to wellbeing. Information given by the oncology nurse may be an important factor for being physically active. Women with breast cancer need to get specific advice about and support in engaging in PA to feel better during chemotherapy treatment. Further research is required to develop guidelines for advice about and support regarding PA during chemotherapy treatment.
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| 43. |
- Young, Emma, 1990-, et al.
(författare)
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EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia
- 2017
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 31:7, s. 1547-1554
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Tidskriftsartikel (refereegranskat)abstract
- Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening (n = 1283) and two validation cohorts (UK CLL4 trial patients, n = 366; CLL Research Consortium (CRC) patients, n = 490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations. EGR2 mutations were detected in 91/2403 (3.8%) investigated cases, and associated with younger age at diagnosis, advanced clinical stage, high CD38 expression and unmutated IGHV genes. EGR2- mutated patients frequently carried ATM lesions (42%), TP53 aberrations (18%) and NOTCH1/FBXW7 mutations (16%). EGR2 mutations independently predicted shorter time-to-first-treatment (TTFT) and overall survival (OS) in the screening cohort; they were confirmed associated with reduced TTFT and OS in the CRC cohort and independently predicted short OS from randomization in the UK CLL4 cohort. A particularly dismal outcome was observed among EGR2-mutated patients who also carried TP53 aberrations. In summary, EGR2 mutations were independently associated with an unfavorable prognosis, comparable to CLL patients carrying TP53 aberrations, suggesting that EGR2-mutated patients represent a new patient subgroup with very poor outcome.
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| 44. |
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