| 1. |
- Boerma, M, et al.
(författare)
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A genetic polymorphism in connexin 37 as a prognostic marker for atherosclerotic plaque development
- 1999
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 246:2, s. 211-218
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Atherosclerosis is a multifactorial disease, in part characterized by chronic inflammatory changes in the vessel wall and loss of normal physical and biochemical interactions between endothelial cells and smooth muscle cells. Previous studies [Hu J., Cotgreave IA. J Clin Invest; 99: 1-5] have provided molecular links between inflammation and myoendothelial communication via gap junctions, suggesting that these structures may be important in the development of the atherosclerotic vessel phenotype. In order to strengthen this premise, the aim of the present work was to probe for structural polymorphisms in connexin 37, a gap junctional protein uniquely expressed in endothelial cells, and to assess for potential genotypic segregation in individuals displaying atherosclerotic plaque. METHODS AND RESULTS: Computer-based comparisons of Expressed Sequence Tags (ESTs) predicted a polymorphism in the human gap junctional protein connexin 37 (cx37). The C1019-T mutation results in a proline to serine shift at codon 319 (cx37*1-cx37*2). A Restriction Fragment Length Polymorphism (RFLP) assay, involving the insertion of a novel Drd I cleavage site in the proline variant revealed a statistically significant over-representation of the cx37*1 allele in association with atherosclerotic plaque-bearing individuals (Odds-ratio for the homozygote = 2.38, Chi2 = 7.693, P = 0.006), in comparison to individuals lacking plaque, irrespective of a history of hypertension. CONCLUSIONS: These data suggest that the C1019-T polymorphism in cx37 may provide 'single gene marker', which could be useful in assessing atherosclerotic plaque development, particularly in cardiovascular risk groups such as those with borderline hypertension.
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| 2. |
- Thulin, Åsa, et al.
(författare)
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Extracellular vesicles in atrial fibrillation and stroke
- 2020
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Ingår i: Thrombosis Research. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0049-3848 .- 1879-2472. ; 193, s. 180-189
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Tidskriftsartikel (refereegranskat)abstract
- Background: Atrial fibrillation (AF) is associated with a 5-fold increased risk of thromboembolic stroke. Extracellular vesicles (EVs) convey pathophysiological information and are possible biomarkers for risk of stroke. Methods: EVs were measured in 836 patients with AF (of which 280 were stroke cases) selected from the ARISTOTLE trial and in a cohort of unselected 70 year old individuals (n = 1007, reference material). EVs from platelets, leukocytes, erythrocytes and inflammatory endothelial cells were measured using flow cytometry and a solid-phase proximity ligation assay. Results: Concentrations of EVs were higher in the ARISTOTLE patients than in the PIVUS cohort for all the EV groups except EVs from endothelial cells (p < 0.0001). The distributions of the concentrations of the EVs were similar among the control group and the stroke cases for all of the sources of EVs in the ARISTOTLE study. EVs were modestly correlated with the levels of NT-ProBNP, Cystatin C, GDF-15 and D-dimer. Stronger correlations were found for platelet EVs as well as phosphatidyl serine positive EVs that were correlated with CD40 ligand in the ARISTOTLE study. Leukocyte EVs were correlated with IL-6 in both the ARISTOTLE and the PIVUS study, implicating them in different physiological processes. Conclusions: Higher levels of EVs were found in anticoagulated patients with AF and a higher risk of stroke than in a general population of similar age, possibly due to the high disease burden in AF patients. Our data with EVs representing a broad repertoire of activated blood cells in AF patients suggest that EVs are likely not a key mediator of occurrence of stroke in this population.
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| 3. |
- Bondeson, Lisa, et al.
(författare)
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Clinical outcomes in cancer patients with COVID-19 in Sweden.
- 2021
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 60:12, s. 1572-1579
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Tidskriftsartikel (refereegranskat)abstract
- The results of studies on the relationship between cancer and COVID-19 have been conflicting and therefore further studies are needed. We aimed to examine the incidence of COVID-19 among patients at one of the largest oncology departments in Sweden, and to evaluate and identify risk factors for poor outcomes, hospital care and death, associated with COVID-19 among cancer patients.This retrospective study included cancer patients at a single center who tested positive for SARS-CoV-2 by PCR either in hospital, primary health care center or commercial laboratory between 1 March and 14 August 2020. Clinical and demographic data were collected from the medical records. Logistic regression analysis was used to identify variables that associated the primary outcomes of need for hospital care and death within 30days of positive test.Of 10,774 patients from the Department of Oncology at Sahlgrenska University Hospital, 135 tested positive for SARS-CoV-2 (1.3%). Twenty-eight patients were excluded from further the data collection since they did not meet the inclusion criteria. Altogether, 107 cancer patients were included and the case fatality rate (CFR) was 12% (13) within 30days of confirmed SARS-CoV-2 infection by PCR. Increasing years of age (OR 1.10; CI 95% 1.03-1.18), palliative treatment intent (OR 15.7; CI 95% 1.8-135.8), and transition to end-of-life care (OR 52.0; CI 95% 3.7-735.6) were associated with increased odds of death within 30days. Male sex was associated with needing hospital care (OR 3.7; CI 95% 1.50-9.1).As in the general population, male sex was found to be at greater risk of needing hospital care for COVID-19, with terminal cancer disease, and older age increasing the odds of fatality. Compared to the general population, slightly more cancer patients had COVID-19. The CFR was within the lower range of others reported in cancer patients.
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| 4. |
- Boyce, SW, et al.
(författare)
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Impact of sodium-hydrogen exchange inhibition by cariporide on death or myocardial infarction in high-risk CABG surgery patients: Results of the CABG surgery cohort of the GUARDIAN study
- 2003
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Ingår i: Journal of Thoracic and Cardiovascular Surgery. - 1097-685X. ; 126:2, s. 420-427
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate the effects of cariporide on all-cause mortality or myocardial infarction at 36 days in patients at risk,of myocardial necrosis after coronary artery bypass graft surgery. Methods: In the coronary artery bypass graft cohort of the GUARD During Ischemia Against Necrosis trial, patients greater than or equal to 18 years who required urgent coronary artery bypass graft, repeat coronary artery bypass graft, or had a history of unstable angina and 2 :2 risk factors (age >65 years, female gender, diabetes mellitus, ejection fraction <35%, or left main or 3-vessel disease) were randomized to placebo (n = 743) or cariporide 20 mg (n = 736), 80 mg (n = 705), or 120 mg (n = 734). A 1-hour intravenous infusion was initiated shortly before surgery and administered every 8 hours for 2 to 7 days. Patients were followed up for 6 months. A nonparametric covariance analysis was used to calculate the primary efficacy endpoint. Results: Baseline characteristics were similar between treatment groups. The cariporide 20- and 80-mg groups had event rates similar to placebo. The endpoint of all-cause mortality or myocardial infarction at day 36 was significant with cariporide 120 mg versus placebo (event rate 12.2% vs 16.2%; P = .027). The risk reduction was evident on postoperative day 1 (3.3% vs 6.5%; P = .005) and was maintained at 6 months (event rate 15.0% vs 18.6%; P = .033). Cariporide was well tolerated, and most adverse events were mild and transient in this high-risk population. Conclusions: Clinical benefit with cariporide 120 mg was observed early after treatment initiation and continued for 6 months postsurgery, suggesting that sodium-hydrogen exchange inhibition with cariporide is cardioprotective in patients undergoing high-risk coronary artery bypass graft surgery.
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| 5. |
- Braunerhjelm, Pontus, et al.
(författare)
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The Relationship Between Domestic and Outward Foreign Direct Investment : The Role of Industry-Specific Effects
- 2005
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Ingår i: International Business Review. - Amsterdam : Elsevier. - 0969-5931 .- 1873-6149. ; 14:6, s. 677-694
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Tidskriftsartikel (refereegranskat)abstract
- Previous research has been inconclusive as regards the effect of outward foreign direct investment (FDI) on domestic investments. In this article, we show that this inconclusiveness can be explained at a disaggregated level as a function of the way industries are organized. Based on a simple theoretical framework including monitoring and trade costs, we argue that a complementary relationship can be expected to prevail in vertically integrated industries, whereas a substitutionary relationship can be expected in horizontally organized production. The empirical analysis confirms a significant difference between the two categories of industry as regards the impact of outward FDI on domestic investment. The results may thus have profound policy implications.
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| 6. |
- Braunerhjelm, Pontus, et al.
(författare)
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The Relationship Between Domestic and Outward ForeignInvestment Revisited : The Impact of Industry-Specific Effects
- 2005
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The ambiguity reported in previous research as regards the effect of foreign direct investment(FDI) on domestic investments is shown to be related to how industries are organized. Basedon a simple model including monitoring and trade costs, we argue that a complementaryrelationship should prevail in vertically integrated industries, whereas a substitutionaryrelationship can be expected in horizontally organized production. Applying iterative SURtechnique,the empirical analysis confirms a significant difference between the two categoriesof industries. To our knowledge, this is the first attempt to reconcile the inconclusivenessreported in previous empirical analyses.
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| 7. |
- de Boer, Hugo J.
(författare)
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Snake Gourds, Parasites and Mother Roasting : Medicinal plants, plant repellents, and Trichosanthes (Cucurbitaceae) in Lao PDR
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background. Traditional plant use was studied in Lao PDR. Research focused on medicinal plant use by the Brou, Saek and Kry ethnic groups, traditional plant repellents against parasitic arthropods and leeches, and the phylogeny and biogeography of the medicinally-important snake gourd genus (Trichosanthes, Cucurbitaceae). Methods. The ethnobiology research used a combination of structured interviews, village surveys, botanical collecting, hydro-distillation, GC-MS analysis, literature studies, and laboratory experiments. The plant systematics research used a combination of morphological studies, molecular biology laboratory work, and phylogenetic, dating and biogeographical analysis. Results. Informants reported the use of close to 100 species to repel arthropods and leeches, many of which have constituents with documented efficacy. Brou, Saek and Kry informants use over 75 plant species for women’s healthcare, mainly during the postpartum period for steam sauna, steam bath, hotbed, mother roasting, medicinal decoctions and infusions, and postpartum diet. A molecular phylogeny of Trichosanthes and Gymnopetalum using a broad sampling of ~60% of their species and 4756 nucleotides of nuclear and plastid DNA shows that Gymnopetalum is nested within Trichosanthes. Fossil-calibrated Bayesian molecular dating of the Trichosanthes phylogeny reveals an early Oligocene origin of the genus, and many of the extant sections originating and diversifying during the Miocene. Biogeographical analysis shows a likely East or South Asian origin of Trichosanthes, with lineages diversifying and spreading throughout Australasia from the early Pliocene to the Pleistocene. Discussion. Traditional plant use in Lao PDR is common and widespread. The presence among the repellent species of economical alternatives to costly synthetic repellents is tenable, and the subject of ongoing studies. Postpartum traditions and medicinal plant use are essential parts of childbirth and postpartum recovery in these ethnic groups, and many other groups in Lao PDR. Efforts to improve maternal healthcare and reduce maternal and infant mortality need to integrate these traditions with modern notions of healthcare to achieve wider adoption. Documenting all possible uses of commonly used medicinal plant species shows that similarity in use between these ethnic groups is relatively low considering that they share, and have shared for many generations, the same environment and resources. A lack of effective cures leads to a process of continuous innovation, where effective cures are shared between cultures, but remedies of only cultural importance, or those under evaluation are culture-specific. The Trichosanthes phylogeny implies the merging of Gymnopetalum into Trichosanthes, and this is done using available names or new combinations. A synopsis of Trichosanthes, the new combinations, and a revision of the species in Australia, are made and presented. Conclusions. Traditional plant use is widespread in Lao PDR, and of significance to many people as a source of primary healthcare and inexpensive repellents. The important medicinal plant genus Trichosanthes includes Gymnopetalum, and has a complex biogeographic history with multiple colonization events of Australasia.
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| 8. |
- Dunberger, Gail, et al.
(författare)
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Cancer survivors' perception of participation in a long-term follow-up study.
- 2013
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Ingår i: Journal of medical ethics. - : BMJ. - 1473-4257 .- 0306-6800. ; 39:1, s. 41-5
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Tidskriftsartikel (refereegranskat)abstract
- Every year medical researchers make contact with a large number of cancer survivors with the aim of evaluating cancer treatment. For this reason we decided to investigate how Swedish cancer survivors perceived their participation in research studies focusing on the long-term consequences of being a survivor of gynaecological or urinary bladder cancer. Data were collected by means of two study-specific postal questionnaires, both consisting of questions covering physical symptoms, well-being and the experience of being a cancer survivor. Both questionnaires also included questions evaluating the participants' experience of being research subjects. The questionnaires were developed in close co-operation with cancer survivors. The study population consisted of 1068 cancer survivors. Of these, 95% (n=1003) reported that they thought the study was valuable and 54% (n=559) that they had been positively affected by participating. Four per cent (n=39) expressed that they had been negatively affected by their participation in the study. The vast majority of the cancer survivors thought that participating in their particular study was valuable.
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| 9. |
- Dyhrfort, Philip, et al.
(författare)
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Monitoring of Protein Biomarkers of Inflammation in Human Traumatic Brain Injury Using Microdialysis and Proximity Extension Assay Technology in Neurointensive Care
- 2019
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Ingår i: Journal of Neurotrauma. - : MARY ANN LIEBERT, INC. - 0897-7151 .- 1557-9042. ; 36:20, s. 2872-2885
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is followed by secondary injury mechanisms strongly involving neuroinflammation. To monitor the complex inflammatory cascade in human TBI, we used cerebral microdialysis (MD) and multiplex proximity extension assay (PEA) technology and simultaneously measured levels of 92 protein biomarkers of inflammation in MD samples every three hours for five days in 10 patients with severe TBI under neurointensive care. One mu L MD samples were incubated with paired oligonucleotide-conjugated antibodies binding to each protein, allowing quantification by real-time quantitative polymerase chain reaction. Sixty-nine proteins were suitable for statistical analysis. We found five different patterns with either early (<48 h; e.g., CCL20, IL6, LIF, CCL3), mid (48-96 h; e.g., CCL19, CXCL5, CXCL10, MMP1), late (>96 h; e.g., CD40, MCP2, MCP3), biphasic peaks (e.g., CXCL1, CXCL5, IL8) or stable (e.g., CCL4, DNER, VEGFA)/low trends. High protein levels were observed for e.g., CXCL1, CXCL10, MCP1, MCP2, IL8, while e.g., CCL28 and MCP4 were detected at low levels. Several proteins (CCL8, -19, -20, -23, CXCL1, -5, -6, -9, -11, CST5, DNER, Flt3L, and SIRT2) have not been studied previously in human TBI. Cross-correlation analysis revealed that LIF and CXCL5 may play a central role in the inflammatory cascade. This study provides a unique data set with individual temporal trends for potential inflammatory biomarkers in patients with TBI. We conclude that the combination of MD and PEA is a powerful tool to map the complex inflammatory cascade in the injured human brain. The technique offers new possibilities of protein profiling of complex secondary injury pathways.
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| 10. |
- Edvinsson, Lars, et al.
(författare)
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Sensory nerve terminal activity in severe hypertension as reflected by circulating calcitonin gene-related peptide (CGRP) and substance P
- 1992
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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 1:4, s. 223-229
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Tidskriftsartikel (refereegranskat)abstract
- In patients with severe hypertension and in age and sex matched controls the circulating levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and substance P-LI were measured. Samples were taken before medication, after 2-4 weeks and 2-12 months of pharmacological treatment to normotension. In the control group CGRP-LI levels were significantly higher for females than for males. No such relation was seen for substance P-LI. There were no correlations between CGRP-LI, substance P-LI or blood pressure. In the untreated acute hypertensive group there was a significant correlation between circulating levels of CGRP-LI and both diastolic and systolic blood pressure. No such relationship was seen for substance P-LI. The plasma levels of substance P-LI were significantly elevated (2.8 +/- 4.0) compared to controls (1.3 +/- 1.3, pmol/l, mean +/- S.D., p < 0.01). The levels of CGRP-LI did not differ from the control group. After 2-4 weeks of treatment the blood pressure decreased significantly and the plasma levels of substance P-LI were normalized while the CGRP-LI still did not differ from that of controls. After 2-12 months of treatment the blood pressure was still normalized, and the plasma levels of CGRP-LI and substance P-LI were not different from the control group. In the present study there was a positive correlation in hypertensives between the circulating CGRP-LI levels and diastolic and systolic blood pressure and elevated levels of substance P-LI. This would implicate the existence of a dynamic control through which the sensory system may register and damp the pressure response.
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