| 1. |
- Raghavan, Maanasa, et al.
(författare)
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Genomic evidence for the Pleistocene and recent population history of Native Americans
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 349:6250
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Tidskriftsartikel (refereegranskat)abstract
- Howand when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican" relict populations, including the historical Mexican Pericues and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.
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| 2. |
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| 3. |
- Bergstrom, Anna, et al.
(författare)
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Acetaminophen Attenuates Pulmonary Vascular Resistance and Pulmonary Arterial Pressure and Inhibits Cardiovascular Collapse in a Porcine Model of Endotoxemia
- 2023
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Ingår i: Shock. - : Shock Society. - 1073-2322 .- 1540-0514. ; 59:3, s. 442-448
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Tidskriftsartikel (refereegranskat)abstract
- Acetaminophen (paracetamol) is often used in critically ill patients with fever and pain; however, little is known about the effects of acetaminophen on cardiovascular function during systemic inflammation. Here, we investigated the effect of acetaminophen on changes in the systemic and pulmonary circulation induced by endotoxin (0.5 μg/kg/h) in anesthetized pigs. Endotoxin infusion led to a rapid increase in pulmonary artery (PA)-pressure and pulmonary vascular resistance index (PVRI). Acetaminophen delayed and attenuated this increase. Furthermore, acetaminophen reduced tachycardia and decreased stroke volume, accompanied by systemic inflammation, without affecting inflammatory parameters such as white blood cell count and TNF-α in blood. As a proof of concept, we injected a high dose of endotoxin (100 μg), which induced rapid cardiovascular collapse in pigs. Pigs treated with acetaminophen survived with no obvious hemodynamic instability during the 50 min observation period. In conclusion, acetaminophen attenuates the effects of endotoxin on pulmonary circulation in anesthetized pigs. This may play a role in severe systemic inflammation.
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| 4. |
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| 5. |
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| 6. |
- Bergstrom, H, et al.
(författare)
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Two different types of hollow-cathode discharges used for high resolution laser spectroscopy on copper
- 1989
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Ingår i: Zeitschrift für Physik D Atoms, Molecules and Clusters. - 0178-7683. ; 13:3, s. 203-206
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Tidskriftsartikel (refereegranskat)abstract
- Two different techniques, Doppler-free saturation spectroscopy on a hollow-cathode discharge and fluorescence spectroscopy on a collimated atomic beam produced from a hollow-cathode discharge, have been used for high-resolution laser-spectroscopy measurements on the 3d10 4p and 5p states in neutral Copper. The relative merits of the two techniques are discussed.
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| 7. |
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| 8. |
- Bjelkmar, Par, et al.
(författare)
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Early outbreak detection by linking health advice line calls to water distribution areas retrospectively demonstrated in a large waterborne outbreak of cryptosporidiosis in Sweden
- 2017
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Ingår i: BMC Public Health. - : BIOMED CENTRAL LTD. - 1471-2458. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the winter and spring of 2011 a large outbreak of cryptosporidiosis occurred in Skelleftea municipality, Sweden. This study summarizes the outbreak investigation in terms of outbreak size, duration, clinical characteristics, possible source(s) and the potential for earlier detection using calls to a health advice line. Methods: The investigation included two epidemiological questionnaires and microbial analysis of samples from patients, water and other environmental sources. In addition, a retrospective study based on phone calls to a health advice line was performed by comparing patterns of phone calls between different water distribution areas. Results: Our analyses showed that approximately 18,500 individuals were affected by a waterborne outbreak of cryptosporidiosis in Skelleftea in 2011. This makes it the second largest outbreak of cryptosporidiosis in Europe to date. Cryptosporidium hominis oocysts of subtype IbA10G2 were found in patient and sewage samples, but not in raw water or in drinking water, and the initial contamination source could not be determined. The outbreak went unnoticed to authorities for several months. The analysis of the calls to the health advice line provides strong indications early in the outbreak that it was linked to a particular water treatment plant. Conclusions: We conclude that an earlier detection of the outbreak by linking calls to a health advice line to water distribution areas could have limited the outbreak substantially.
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| 9. |
- Challis, Pontus, et al.
(författare)
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Factors associated with the increased incidence of necrotising enterocolitis in extremely preterm infants in Sweden between two population-based national cohorts (2004-2007 vs 2014-2016)
- 2024
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Ingår i: Archives of Disease in Childhood. - : BMJ Publishing Group Ltd. - 1359-2998 .- 1468-2052. ; 109:1, s. 87-93
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate potential risk factors behind the increased incidence of necrotising enterocolitis (NEC) in Swedish extremely preterm infants.Design Registry data from two population-based national cohorts were studied. NEC diagnoses (Bell stage >= II) were validated against hospital records.Patients All liveborn infants <27 weeks of gestation 2004-2007 (n=704) and 2014-2016 (n=895) in Sweden.Main outcome measures NEC incidence.Results The validation process resulted in a 28% reduction of NEC cases but still confirmed a higher NEC incidence in the later epoch compared with the earlier (73/895 (8.2%) vs 27/704 (3.8%), p=0.001), while the composite of NEC or death was lower (244/895 (27.3%) vs 229/704 (32.5%), p=0.022). In a multivariable Cox regression model, censored for mortality, there was no significant difference in early NEC (0-7 days of life) between epochs (HR=0.9 (95% CI 0.5 to 1.9), p=0.9), but being born in the later epoch remained an independent risk factor for late NEC (>7 days) (HR=2.7 (95% CI 1.5 to 5.0), p=0.001). In propensity score analysis, a significant epoch difference in NEC incidence (12% vs 2.8%, p<0.001) was observed only in the tertile of infants at highest risk of NEC, where the 28-day mortality was lower in the later epoch (35% vs 50%, p=0.001). More NEC cases were diagnosed with intramural gas in the later epoch (33/73 (45.2%) vs 6/26 (23.1%), p=0.047).Conclusions The increase in NEC incidence between epochs was limited to cases occurring after 7 days of life and was partly explained by increased survival in the most extremely preterm infants. Misclassification of NEC is common.
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| 10. |
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| 11. |
- Eriksson, Mats, et al.
(författare)
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Biotic dynamics and carbonate microfacies of the conspicuous Darriwilian (Middle Ordovician) 'Taljsten' interval, south-central Sweden
- 2012
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Ingår i: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier BV. - 1872-616X .- 0031-0182. ; 367, s. 89-103
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Tidskriftsartikel (refereegranskat)abstract
- Enclosed in the Darriwilian (Middle Ordovician) part of the reddish 'orthoceratite limestone' of Baltoscandia is a conspicuous c. 1.5 m thick unit colloquially known as the 'Taljsten' interval. It has a wide geographical distribution in the Baltoscandian paleocontinent but is particularly well exposed in south-central Sweden. The unit is characterized by its deviant gray color and beds with a mass occurrence of cystoid echinoderms. Moreover, the recent discovery of an anomalous abundance of extraterrestrial chromite grains and micrometeorites in the 'Taljsten' and immediately adjacent strata bear witness of a time of deposition correlating to an increased influx of extraterrestrial matter to Earth. In this study we analyze the faunal dynamics, based primarily on microfossils and carbonate microfacies, across this intriguing interval. Generally known as a macrolithologically monotonous succession, the 'Taljsten' proved more heterogeneous than previously believed in terms of fossil content and preservation, as well as mineral content and composition. The general texture is wackestone/packstone, but local heterogeneities are frequent. A microfaunal reorganization occurred with a transition from a trilobite- and brachiopod-dominated community to one dominated by echinoderms, which is mirrored also macroscopically by the cystoids. The latter pelmatozoans seem to have flourished and might even have aided in the formation of the numerous hardgrounds. The increase in echinoderms is linked to a Volkhovian increase in echinoderms in eastern Baltica. In the immediate post-'Taljsten' strata there is no distinct change back to the pre-'Taljsten' biota. Conodont and ostracod faunal diversity data reveal peak values in the 'Taljsten' compared to the enclosing strata, suggesting that the paleoenvironment was more suitable for higher diversity faunas of these metazoan groups. All data collectively support a regression in the beginning of the 'Taljsten', likely followed by transgression in its upper part. (C) 2012 Elsevier B.V. All rights reserved.
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| 12. |
- Farooqi, Aijaz, et al.
(författare)
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One-year survival and outcomes of infants born at 22 and 23 weeks of gestation in Sweden 2004-2007, 2014-2016 and 2017-2019
- 2024
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Ingår i: Archives of Disease in Childhood-Fetal and Neonatal Edition. - : BMJ Publishing Group Ltd. - 1359-2998 .- 1468-2052. ; 109:1, s. 10-17
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo explore associations between perinatal activity and survival in infants born at 22 and 23 weeks of gestation in Sweden. Design/SettingData on all births at 22 and 23 weeks' gestational age (GA) were prospectively collected in 2004-2007 (T1) or obtained from national registers in 2014-2016 (T2) and 2017-2019 (T3). Infants were assigned perinatal activity scores based on 3 key obstetric and 4 neonatal interventions. Main outcomeOne-year survival and survival without major neonatal morbidities (MNM): intraventricular haemorrhage grade 3-4, cystic periventricular leucomalacia, surgical necrotising enterocolitis, retinopathy of prematurity stage 3-5 or severe bronchopulmonary dysplasia. The association of GA-specific perinatal activity score and 1-year survival was also determined. Results977 infants (567 live births and 410 stillbirths) were included: 323 born in T1, 347 in T2 and 307 in T3. Among live-born infants, survival at 22 weeks was 5/49 (10%) in T1 and rose significantly to 29/74 (39%) in T2 and 31/80 (39%) in T3. Survival was not significantly different between epochs at 23 weeks (53%, 61% and 67%). Among survivors, the proportions without MNM in T1, T2 and T3 were 20%, 17% and 19% for 22 weeks and 17%, 25% and 25% for 23 weeks' infants (p>0.05 for all comparisons). Each 5-point increment in GA-specific perinatal activity score increased the odds for survival in first 12 hours of life (adjusted OR (aOR) 1.4; 95% CI 1.3 to 1.6) in addition to 1-year survival (aOR 1.2; 95% CI 1.1 to 1.3), and among live-born infants it was associated with increased survival without MNM (aOR 1.3; 95% CI 1.1 to 1.4). ConclusionIncreased perinatal activity was associated with reduced mortality and increased chances of survival without MNM in infants born at 22 and 23 weeks of GA.
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| 13. |
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| 14. |
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| 15. |
- Hagstrom, Emil, et al.
(författare)
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IMPACT OF BODY WEIGHT AT AGE 20 AND WEIGHT GAIN DURING ADULTHOOD ON MIDLIFE CORONARY ARTERY CALCIUM IN 15,000 MEN AND WOMEN : AN INTERIM ANALYSIS OF THE SWEDISH CARDIOPULMONARY BIOIMAGE STUDY
- 2019
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 73:9, s. 1692-1692
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundElevated body weight in adolescence is strongly associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, or to weight gain with subsequent high adult weight is not known. Using data from the Swedish CArdioPulmonary bioImage Study (SCAPIS), we investigated the association between weight at age 20, weight gain to midlife and coronary artery calcium score (CACS) at midlife.MethodsIn the first 15,810 participants in SCAPIS (mean age 58 years, 52% women), data on CACS at midlife, self-reported body weight at age 20 and weight at examination in SCAPIS were recorded.ResultsCACS in midlife was significantly higher with increasing weight at age 20 (p<0.001 for both sexes), and then increased with weight gain until midlife at all levels of body weight at age 20 after adjusting for age, height, smoking, alcohol intake, education level, exercise levels and LDL cholesterol. However, the association with weight gain was only significant in men (p = 0.047), not in women (p=0.474). No significant interaction was seen between weight at age 20 and midlife weight with CACS. The effect of weight at age 20 on CACS was significantly more marked in men than in women, as was the effect of weight gain (p<0.001 for both interactions).ConclusionWeight at age 20 and weight gain to midlife were both related to CACS, but much more markedly so in men than in women, indicating a generally larger effect of both early adult weight and further weight gain until midlife on CACS in men, compared to women.
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| 16. |
- Henriksson, Anders E., et al.
(författare)
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Identification of Potential Plasma Biomarkers for Abdominal Aortic Aneurysm Using Tandem Mass Tag Quantitative Proteomics
- 2018
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Ingår i: Proteomes. - : MDPI AG. - 2227-7382. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- Plasma biomarkers that identify abdominal aortic aneurysm (AAA) rupture risk would greatly assist in stratifying patients with small aneurysms. Identification of such biomarkers has hitherto been unsuccessful over a range of studies using different methods. The present study used an alternative proteomic approach to find new, potential plasma AAA biomarker candidates. Pre-fractionated plasma samples from twelve patients with AAA and eight matched controls without aneurysm were analyzed by mass spectrometry applying a tandem mass tag (TMT) technique. Eight proteins were differentially regulated in patients compared to controls, including decreased levels of the enzyme bleomycin hydrolase. The down-regulation of this enzyme was confirmed in an extended validation study using an enzyme-linked immunosorbent assay (ELISA). The TMT-based proteomic approach thus identified novel potential plasma biomarkers for AAA.
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| 17. |
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| 18. |
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| 19. |
- Jeppsson, Anders, 1960, et al.
(författare)
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Preoperative supplementation with fibrinogen concentrate in cardiac surgery: A randomized controlled study
- 2016
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912. ; 116:2, s. 208-214
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bleeding remains a severe complication in cardiac surgery. Several studies have found an association between the preoperative plasma concentration of fibrinogen and postoperative bleeding in cardiac surgery patients. This raises the question of whether preoperative supplementation with fibrinogen concentrate can reduce postoperative blood loss. Methods: An investigator-initiated, prospective, randomized double-blind placebo-controlled study, was performed in 48 low-risk, coronary artery bypass grafting patients. Subjects were randomized to infusion of 2 g fibrinogen or placebo immediately before surgery, after induction of anaesthesia. The primary endpoint was blood loss during the first 12 h postoperatively. Secondary endpoints included the proportion of transfused subjects, the number of transfused allogeneic blood products (red blood cells, plasma and platelets), and haemoglobin concentration after surgery. Student's t-test and Mann-Whitney U-test was used to compare continuous data and chi(2)-test to compare categorical data between groups. Results: Median postoperative bleedingwas not significantly different between the fibrinogen and placebo groups [650 (25/75th percentile 500. 835) ml compared with 730 (543. 980) ml, P=0.29]. The proportion of transfused subjects (33 vs 29%, P=0.76), number of perioperative transfusions of allogeneic blood products (0 (0-2 vs 0 (0-3), P=0.76) and haemoglobin concentration 24 h after surgery (107 (SD 11) vs 100 (12) g L-1, P=0.07) were not significantly different between the fibrinogen and placebo group, respectively. Conclusions: Preoperative supplementation with 2 g fibrinogen concentrate did not significantly influence postoperative bleeding, in coronary artery bypass grafting patients without documented hypofibrinogenaemia.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Naessen, Sabine, et al.
(författare)
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Autoimmune Disease in Turner Syndrome in Sweden : An up to 25 Years' Controlled Follow-up Study
- 2024
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 109:2, s. e602-e612
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Tidskriftsartikel (refereegranskat)abstract
- Context: Turner syndrome (TS) is the most common chromosomal aberration in women; it is the result of structural or numeric abnormalities in the X chromosome. Autoimmune hypothyroidism has been recognized as one of the more prominent disorders associated with TS.Objective: This work aimed to study the prevalence of autoimmune diseases in TS.Methods: A cross-sectional, longitudinal, 25-year follow-up study was conducted of patients from adult Turner centers at the University Hospitals, Sweden. During 1994 to 2020, a total of 503 women aged 16 to 71 years with TS were evaluated consecutively every fifth year according to national guidelines. A random population sample of women, n = 401, aged 25 to 44 years, from the World Health Organization Monitoring of Trends and Determinants for Cardiovascular Disease (MONICA) project served as controls. Serum thyrotropin, free thyroxine, vitamin B-12, antithyroid peroxidase (anti-TPO), and antitransglutaminase antibodies were measured.Results: Mean follow-up time (years) was 16 +/- 7 for patients and 13 +/- 1 for controls. From study start, the prevalence increased in TS for hypothyroidism 40% to 58%, vitamin B-12 deficiency 5% to 12%, celiac disease 4% to 7%, positive anti-TPO 26% to 41%, and antitransglutaminase antibodies 6% to 8% (P < .0001 vs controls). Type 1 diabetes and Addison disease were rare. The only interrelationship was between hypothyroidism and vitamin B-12 deficiency, both in TS and controls. No association between autoimmune disease and karyotype, antecedent growth hormone treatment, or ongoing estrogen hormone replacement, was seen in TS.Conclusion: In women with TS up to older than 80 years, more than half developed hypothyroidism, mainly autoimmune, during follow-up. Awareness of vitamin B-12 deficiency and celiac disease throughout life is also recommended in women with TS.
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| 24. |
- Neiman, Maja, 1983-, et al.
(författare)
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Individual and stable autoantibody repertoires in healthy individuals
- 2019
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Ingår i: Autoimmunity. - : TAYLOR & FRANCIS LTD. - 0891-6934 .- 1607-842X. ; 52:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- In the era towards precision medicine, we here present the individual specific autoantibody signatures of 193 healthy individuals. The self-reactive IgG signatures are stable over time in a way that each individual profile is recognized in longitudinal sampling. The IgG autoantibody reactivity towards an antigen array comprising 335 protein fragments, representing 204 human proteins with potential relevance to autoimmune disorders, was measured in longitudinal plasma samples from 193 healthy individuals. This analysis resulted in unique autoantibody barcodes for each individual that were maintained over one year's time. The reactivity profiles, or signatures, are person specific in regards to the number of reactivities and antigen specificity. Two independent data sets were consistent in that each healthy individual displayed reactivity towards 0-16 antigens, with a median of six. Subsequently, four selected individuals were profiled on in-house produced high-density protein arrays containing 23,000 protein fragments representing 14,000 unique protein coding genes. Based on a unique, broad and deep longitudinal profiling of autoantibody reactivities, our results demonstrate a unique autoreactive profile in each analyzed healthy individual. The need and interest for broad-ranged and high-resolution molecular profiling of healthy individuals is rising. We have here generated and assessed an initial perspective on the global distribution of the self-reactive IgG repertoire in healthy individuals, by investigating 193 well-characterized healthy individuals.
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| 25. |
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| 26. |
- Nilsson, Anders, 1958, et al.
(författare)
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Results from a degradable TMC joint Spacer (Artelon) compared with tendon arthroplasty
- 2005
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Ingår i: J Hand Surg [Am]. - : Elsevier BV. - 0363-5023. ; 30:2, s. 380-9
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: A new spacer for the trapeziometacarpal joint (TMC) based on a biological and tissue-preserving concept for the treatment of TMC osteoarthritis (OA) has been evaluated. The purpose was to combine a spacing effect with stabilization of the TMC joint. METHODS: Artelon (Artimplant AB, Sweden) TMC Spacer is synthesized of a degradable polyurethaneurea (Artelon), which has been shown to be biocompatible over time and currently is used in ligament augmentation procedures. Fibers of the polymer were woven into a T-shaped device in which the vertical portion separates the bone edges of the TMC joint and the horizontal portion stabilizes the joint. Fifteen patients with disabling pain and isolated TMC OA were included in the study. Ten patients received the spacer device and the remaining 5 (control group) were treated with a trapezium resection arthroplasty with abductor pollicis longus (APL) stabilization. The median ages of the 2 groups were 60 and 59 years, respectively. Pain, strength, stability, and range of motion were measured before and after surgery. Radiographic examination was performed in all patients before and after surgery. At follow-up evaluation 3 years after surgery an unbiased observer evaluated all patients. Biopsy specimens were obtained from 1 patient 6 months after surgery. RESULTS: All patients were stable clinically without signs of synovitis. In both groups all patients were pain free. The median values for both key pinch and tripod pinch increased compared with before surgery in the spacer group but not in the APL group. The biopsy examinations showed incorporation of the device in the surface of the adjacent bone and the surrounding connective tissue. No signs of foreign-body reaction were seen. CONCLUSIONS: This study showed significantly better pinch strength after Artelon TMC Spacer implantation into the TMC joint compared with APL arthroplasty.
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| 27. |
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| 28. |
- Pinzke, Anders, et al.
(författare)
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Gamma-rays from dark matter annihilations strongly constrain the substructure in halos
- 2009
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 103:18, s. 181302-
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Tidskriftsartikel (refereegranskat)abstract
- Recently, it has been shown that electrons and positrons from dark matter (DM) annihilations provide an excellent fit to the Fermi, PAMELA, and HESS data. Using this DM model, which requires an enhancement of the annihilation cross section over its standard value to match the observations, we show that it immediately implies an observable level of gamma-ray emission for the Fermi telescope from nearby galaxy clusters such as Virgo and Fornax. We show that this DM model implies a peculiar feature from final state radiation that is a distinctive signature of DM. Using the EGRET upper limit on the gamma-ray emission from Virgo, we constrain the minimum mass of substructures within DM halos to be > 5x10^-3 M_sun -- about four orders of magnitudes larger than the expectation for cold dark matter. This limits the cutoff scale in the linear matter power spectrum to k < 35/kpc which can be explained by e.g., warm dark matter. Very near future Fermi observations will strongly constrain the minimum mass to be > 10^3 M_sun: if the true substructure cutoff is much smaller than this, the DM interpretation of the Fermi/PAMELA/HESS data must be wrong. To address the problem of astrophysical foregrounds, we performed high-resolution, cosmological simulations of galaxy clusters that include realistic cosmic ray (CR) physics. We compute the dominating gamma-ray emission signal resulting from hadronic CR interactions and find that it follows a universal spectrum and spatial distribution. If we neglect the anomalous enhancement factor and assume standard values for the cross section and minimum subhalo mass, the same model of DM predicts comparable levels of the gamma-ray emission from DM annihilations and CR interactions. This suggests that spectral subtraction techniques could be applied to detect the annihilation signal.
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| 29. |
- Ribom, Dan, et al.
(författare)
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Positron emission tomography 11C-methionine and survival in patients with low-grade gliomas
- 2001
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Ingår i: Cancer. - 0008-543X .- 1097-0142. ; 92:6, s. 1541-1549
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDConsiderable numbers of patients with low-grade gliomas experience an early malignant course and may benefit from aggressive treatment. These patients are difficult to identify using established prognostic factors. A retrospective study was performed to determine whether the 11C-methionine uptake in tumor is a survival factor in adult patients with supratentorial gliomas classified as World Health Organization Grade 2.METHODSThe authors identified 89 patients with histologically confirmed low-grade gliomas in whom an 11C-methionine positron emission tomography (PET) scan had been performed as part of the diagnostic tumor investigation from 1983 to 1998. Clinical data were collected, and the PET scans were re-evaluated according to a fixed protocol. The 11C-methionine uptake in the tumor and relevant clinical parameters were entered into univariate and multivariate survival analyses.RESULTSAt the end of the study, 49 patients (55.1%) had died. The median overall survival was 5.7 years. Low methionine uptake was significantly favorable in the multivariate survival analysis (P = 0.04) along with oligodendroglioma (P = 0.003). In the histologic subgroups, 11C-methionine uptake was an important survival factor among patients with astrocytomas (P = 0.05) and oligodendrogliomas (P = 0.03). Tumor resection was a favorable prognostic factor in patients with high methionine uptake (P = 0.01) but not in patients with low uptake.CONCLUSIONSBaseline 11C-methionine PET is a prognostic indicator in patients with low-grade gliomas. The results imply that PET is a valuable tool in the clinical management of these patients and may assist in the selection of patients for therapy.
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| 30. |
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| 31. |
- Sandelin, Martin, et al.
(författare)
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Patients with Non-small Cell Lung Cancer Analyzed for EGFR : Adherence to Guidelines, Prevalence and Outcome
- 2015
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 35:7, s. 3979-3985
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidermal growth factor receptor (EGFR) analysis is the first molecular test introduced in the routine care of patients with non-small cell lung cancer (NSCLC). In the present study, we describe the prevalence of EGFR mutations and the adherence to testing and treatment guidelines in a population-based Swedish NSCLC cohort. Materials and Methods: Patients with NSCLC analyzed for EGFR mutations were identified and their characteristics and survival data were retrieved. We compared the study cohort to a matched lung cancer population. Results: The EGFR mutation frequency was 10%. Mutations were enriched in women and in adenocarcinoma cases. Out of patients with advanced-stage NSCLC with non-squamous histology, only 49% were referred for EGFR analysis. Out of the patients with EGFR mutation and advanced disease, only 38% received EGFR-tyrosine kinase inhibitor (TKI) in first-line therapy. Conclusion: The EGFR-mutated NSCLC population studied is similar to other Western populations. Surprisingly, a large proportion of patients were not referred for EGFR analysis. Out of the patients with EGFR mutation, fewer than 40% received EGFR-TKI as first-line treatment. Our results highlight the need for follow-up of treatment and diagnostic algorithms in routine healthcare.
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| 32. |
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| 33. |
- Shev, Steven, et al.
(författare)
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Herpes simplex virus-2 may increase susceptibility of the sexual transmission of hepatitis C
- 1995
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Ingår i: Sexually Transmitted Diseases. - 1537-4521. ; 22:4, s. 210-216
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Antibodies against herpes simplex viruses-1 and -2, cytomegalovirus, and syphilis were determined in six heterosexual couples with strong indications of having sexually transmitted hepatitis C virus infection and in 17 other heterosexual couples in which one partner was hepatitis C virus viremic (source partner), but the other had remained hepatitis C virus uninfected (exposed partner). STUDY DESIGN. Antibody testing was done with an enzyme-linked immunosorbent assay. Anti-herpes simplex virus 2 and anti-hepatitis C virus findings were further confirmed by immunoblotting. Hepatitis C virus RNA was determined by polymerase chain reaction and genotyped with type-specific primers. RESULTS. Five of six anti-hepatitis C virus-positive exposed heterosexual partners without parenteral risk factors, compared with three of 17 anti-hepatitis C virus-negative exposed partners, had antibodies to herpes simplex virus-2. On the other hand, no statistically significant difference was found regarding the frequency of herpes simplex virus-2 seropositivity when source partners in the anti-hepatitis C virus concordant and discordant couples were compared. The presence of antibodies to herpes simplex virus-1, cytomegalovirus, and syphilis did not significantly differ between source or exposed partners in anti-hepatitis C virus concordant and discordant couples, respectively. No predominance of any one hepatitis C virus genotype or liver morphology in couples concordant compared with discordant for anti-hepatitis C virus was found. CONCLUSIONS. The findings support the role of herpes simplex virus-2 in the heterosexual transmission of hepatitis C virus infections, and more specifically an increase in susceptibility to hepatitis C virus infections in exposed heterosexual partners with antibodies to herpes simplex virus-2.
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| 34. |
- Sjöwall, Johanna, et al.
(författare)
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Innate immune responses in Lyme borreliosis : Enhanced tumour necrosis factor-a and interleukin-12 in asymptomatic individuals in response to live spirochetes
- 2005
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 141:1, s. 89-98
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Tidskriftsartikel (refereegranskat)abstract
- Innate immunity is important for early defence against borrelia spirochetes and should play a role in the clinical outcome of the infection. In order to study early cytokine responses, in vitro differentiated dendritic cells (DCs) and whole blood cells from 21 patients with different clinical outcomes of Lyme neuroborreliosis were stimulated with live borrelia spirochetes. The borrelia-induced secretion of interleukin (IL)-4, IL-10, IL-12p70, Interferon (INF)-? and tumour necrosis factor (TNF)-a in DCs and IL-1ß, IL-6, IL-8, IL-10, IL-12p70, TNF-a, regulated upon activation normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1a, MIP-1ß and eotaxin in whole blood cells was measured by enzyme-linked immunospot (ELISPOT) and multiplex arrays, respectively. We found increased numbers of TNF-a-secreting DCs (P = 0.018) in asymptomatic seropositive individuals compared to patients with subacute neuroborreliosis and seronegative controls. Asymptomatic individuals were also found to have elevated levels of IL-12p70 (P = 0.031) in whole blood cell supernatants compared to seronegative controls. These results are in line with previous experiments using cells of the adaptive immune response, indicating that strong T helper type 1 (Th1) proinflammatory responses might be associated with a successful resolution of Lyme disease. © 2005 British Society for Immunology.
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| 35. |
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| 36. |
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| 37. |
- Thimour-Bergstrom, L., et al.
(författare)
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Triclosan-coated sutures reduce surgical site infection after open vein harvesting in coronary artery bypass grafting patients: a randomized controlled trial(dagger)
- 2013
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Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 44:5, s. 931-938
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of surgical site infection (SSI) after open vein harvesting in coronary artery bypass grafting (CABG) patients ranges in different studies between 2 and 20%. Triclosan is an antibacterial substance that reduces the growth of bacteria by inhibiting fatty acid synthesis. We hypothesized that wound closure with triclosan-coated sutures would reduce SSI after open vein harvesting. An investigator-initiated prospective randomized double-blind single-centre study was performed with 374 patients, randomized to subcutaneous and intracutaneous leg-wound closure with either triclosan-coated sutures (Vicryl Plus((R)) and Monocryl Plus((R)), Ethicon, Somerville, NJ, USA) (n = 184) or identical sutures without triclosan (n = 190) from the same manufacturer. All patients were followed up after 30 days (clinical visit) and 60 days (telephone interview). Primary endpoint was SSI within 60 days after surgery according to the definition of Center for Disease Control. Predefined secondary endpoints included culture-proven and antibiotic-treated SSI. The primary endpoint occurred in 23 patients (12.5%) with triclosan-coated sutures and in 38 patients (20.0%) in the group without triclosan (P = 0.0497, risk ratio 0.63, (95% confidence interval 0.39-1.00). Corresponding figures for culture-proven infections were 7.6 vs 12.1%, (P = 0.15), and for antibiotic-treated infections, 10.9 vs 18.4%, (P = 0.039). Staphylococcus aureus and coagulase-negative staphylococci were the most common pathogens in both groups. Insulin-treated diabetes and vein-harvesting time were associated with SSI after vein harvesting. Leg-wound closure with triclosan-coated sutures in CABG patients reduces SSIs after open vein harvesting. (ClinicalTrials.gov number NCT01212315).
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| 38. |
- Toren, K., et al.
(författare)
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Measures of bronchodilator response of FEV1, FVC and SVC in a Swedish general population sample aged 50-64 years, the SCAPIS Pilot Study
- 2017
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - : DOVE MEDICAL PRESS LTD. - 1176-9106 .- 1178-2005. ; 12, s. 973-980
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data are lacking from general population studies on how to define changes in lung function after bronchodilation. This study aimed to analyze different measures of bronchodilator response of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and slow vital capacity (SVC). Materials and methods: Data were derived from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) Pilot study. This analysis comprised 1,050 participants aged 50-64 years from the general population. Participants were investigated using a questionnaire, and FEV1, FVC and SVC were recorded before and 15 minutes after inhalation of 400 mu g of salbutamol. A bronchodilator response was defined as the relative change from baseline value expressed as the difference in units of percent predicted normal. Predictors of bronchodilator responses were assessed using multiple linear regression models. Airway obstruction was defined as FEV1/FVC ratio below lower limit of normal (LLN) before bronchodilation, and COPD was defined as an FEV1/FVC ratio below LLN after bronchodilation. Physician-diagnosed asthma was defined as an affirmative answer to " Have you ever had asthma diagnosed by a physician?". Asymptomatic never-smokers were defined as those not reporting physician-diagnosed asthma, physician-diagnosed COPD or emphysema, current wheeze or chronic bronchitis and being a lifelong never-smoker. Results: Among all subjects, the greatest bronchodilator responses (FEV1, FVC and SVC) were found in subjects with asthma or COPD. The upper 95th percentile of bronchodilator responses in asymptomatic never-smokers was 8.7% for FEV1, 4.2% for FVC and 5.0% for SVC. The bronchodilator responses were similar between men and women. In a multiple linear regression model comprising all asymptomatic never-smokers, the bronchodilator response of FEV1 was significantly associated with airway obstruction and height. Conclusion: When the bronchodilator response in asymptomatic never-smokers is reported as the difference in units of predicted normal, significant reversibility of FEV1, FVC and SVC to bronchodilators is 9%, 4% and 5%, respectively.
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| 39. |
- Toren, Kjell, et al.
(författare)
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Vital capacity and COPD : the Swedish CArdioPulmonary bioImage Study (SCAPIS)
- 2016
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - : DOVE MEDICAL PRESS LTD. - 1176-9106 .- 1178-2005. ; 11, s. 927-933
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Tidskriftsartikel (refereegranskat)abstract
- Background: Spirometric diagnosis of chronic obstructive pulmonary disease (COPD) is based on the ratio of forced expiratory volume in 1 second (FEV1)/vital capacity (VC), either as a fixed value <0.7 or below the lower limit of normal (LLN). Forced vital capacity (FVC) is a proxy for VC. The first aim was to compare the use of FVC and VC, assessed as the highest value of FVC or slow vital capacity (SVC), when assessing the FEV1/VC ratio in a general population setting. The second aim was to evaluate the characteristics of subjects with COPD who obtained a higher SVC than FVC. Methods: Subjects (n=1,050) aged 50-64 years were investigated with FEV1, FVC, and SVC after bronchodilation. Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPDFVC was defined as FEV1/FVC <0.7, GOLDCOPD(VC) as FEV1/VC <0.7 using the maximum value of FVC or SVC, LLNCOPDFVC as FEV1/FVC below the LLN, and LLNCOPDVC as FEV1/VC below the LLN using the maximum value of FVC or SVC. Results: Prevalence of GOLDCOPD(FVC) was 10.0% (95% confidence interval [CI] 8.2-12.0) and the prevalence of LLNCOPDFVC was 9.5% (95% CI 7.8-11.4). When estimates were based on VC, the prevalence became higher; 16.4% (95% CI 14.3-18.9) and 15.6% (95% CI 13.5-17.9) for GOLDCOPD(VC) and LLNCOPDVC, respectively. The group of additional subjects classified as having COPD based on VC, had lower FEV1, more wheeze and higher residual volume compared to subjects without any COPD. Conclusion: The prevalence of COPD was significantly higher when the ratio FEV1/VC was calculated using the highest value of SVC or FVC compared with using FVC only. Subjects classified as having COPD when using the VC concept were more obstructive and with indications of air trapping. Hence, the use of only FVC when assessing airflow limitation may result in a considerable under diagnosis of subjects with mild COPD.
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| 40. |
- Wechalekar, Ashutosh, et al.
(författare)
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Pharmacodynamic evaluation and safety assessment of treatment with antibodies to serum amyloid P component in patients with cardiac amyloidosis : an open-label Phase 2 study and an adjunctive immuno-PET imaging study
- 2022
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Ingår i: BMC Cardiovascular Disorders. - : BioMed Central (BMC). - 1471-2261 .- 1471-2261. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background In a Phase I study treatment with the serum amyloid P component (SAP) depleter miridesap followed by monoclonal antibody to SAP (dezamizumab) showed removal of amyloid from liver, spleen and kidney in patients with systemic amyloidosis. We report results from a Phase 2 study and concurrent immuno-positron emission tomography (PET) study assessing efficacy, pharmacodynamics, pharmacokinetics, safety and cardiac uptake (of dezamizumab) following the same intervention in patients with cardiac amyloidosis. Methods Both were uncontrolled open-label studies. After SAP depletion with miridesap, patients received <= 6 monthly doses of dezamizumab in the Phase 2 trial (n = 7), <= 2 doses of non-radiolabelled dezamizumab plus [Zr-89]Zr-dezamizumab (total mass dose of 80 mg at session 1 and 500 mg at session 2) in the immuno-PET study (n = 2). Primary endpoints of the Phase 2 study were changed from baseline to follow-up (at 8 weeks) in left ventricular mass (LVM) by cardiac magnetic resonance imaging and safety. Primary endpoint of the immuno-PET study was [Zr-89]Zr-dezamizumab cardiac uptake assessed via PET. Results Dezamizumab produced no appreciable or consistent reduction in LVM nor improvement in cardiac function in the Phase 2 study. In the immuno-PET study, measurable cardiac uptake of [Zr-89]Zr-dezamizumab, although seen in both patients, was moderate to low. Uptake was notably lower in the patient with higher LVM. Treatment-associated rash with cutaneous small-vessel vasculitis was observed in both studies. Abdominal large-vessel vasculitis after initial dezamizumab dosing (300 mg) occurred in the first patient with immunoglobulin light chain amyloidosis enrolled in the Phase 2 study. Symptom resolution was nearly complete within 24 h of intravenous methylprednisolone and dezamizumab discontinuation; abdominal computed tomography imaging showed vasculitis resolution by 8 weeks. Conclusions Unlike previous observations of visceral amyloid reduction, there was no appreciable evidence of amyloid removal in patients with cardiac amyloidosis in this Phase 2 trial, potentially related to limited cardiac uptake of dezamizumab as demonstrated in the immuno-PET study. The benefit-risk assessment for dezamizumab in cardiac amyloidosis was considered unfavourable after the incidence of large-vessel vasculitis and development for this indication was terminated. Trial registration NCT03044353 (2 February 2017) and NCT03417830 (25 January 2018).
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| 41. |
- Örlefors, Håkan
(författare)
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Positron Emission Tomography in the Management of Neuroendocrine Tumors
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neuroendocrine tumors (NET´s) are often characterized by overproduction of peptide hormones. In spite of pronounced clinical symptoms, the tumor lesions can be small and difficult to detect. The general aim of this thesis was to investigate, in vitro and in vivo, some of the potential monoamine pathways present in NET´s, using radiolabeled tracers for positron emission tomography (PET), with the intention to explore the value of PET-imaging in the management of NET´s. We used the 11C-labeled serotonin precursor 5-hydroxy tryptophan (HTP) as the tracer for imaging of NET´s. More than 95% of the subjects displayed a high tracer uptake on PET and tumor detection rate with PET was higher in >50% of the patients compared both to computed tomography (CT) and somatostatin receptor scintigraphy (SRS). The primary tumor was imaged by PET in 84% (16/19), compared to 47% and 42% for SRS and CT, respectively. Tumor visibility was better with PET due to a higher tumor-to-background ratio and a better spatial resolution. There was a strong correlation (r = .907) between changes in urinary-5-hydroxy indole acetic acid and changes in transport rate of 11C-5-HTP during treatment, indicating the use of PET in treatment monitoring of NET´s. Pretreatment with carbidopa decreased the urinary radioactivity concentration four-fold and significantly (p<0.001) increased the tumor tracer uptake. This greatly improved image interpretation and tumor lesion detection. A screening for expression of monoamine pathways in NET´s revealed a high in vitro binding of the monoamineoxidase-A ligand harmine to tumor sections. PET examinations with 11C-harmine could visualize tumors in all patients, including non-functioning endocrine pancreatic tumors (EPT´s). Finally, the in vitro turnover and in vivo distribution of the amino acids glutamate, glutamine and aspartate was investigated. Limited uptake in vivo indicates the lack of utility for these substances as PET-tracers for imaging and characterization of NET´s.
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