| 1. |
- Hartford, Marianne, 1944, et al.
(författare)
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Plasma renin activity has a complex prognostic role in patients with acute coronary syndromes.
- 2021
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 329, s. 198-204
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Plasma renin activity (PRA) has been related to all-cause mortality and cardiovascular events in patients with cardiovascular disease. However, data from patients with acute coronary syndromes (ACS) are sparse.METHODS: Determination of PRA was made in 550 patients with ACS, including a subgroup of 287 patients not on treatment with angiotensin converting enzyme inhibitors, angiotensin receptor blockers or diuretics, and without heart failure. We evaluated the relations between PRA and all-cause mortality after three years and long-term, and to cardiovascular events after median 8.7 years. Adjustments were made for variables that influenced the hazard ratio (HR) > 5% for the relation between PRA and outcome.RESULTS: Baseline PRA was associated with all-cause mortality during three-years (unadjusted HR 1.74 per 1 SD increase in logarithmically transformed PRA; 95% confidence interval (CI) 1.39-2.16, p < 0.0001) and long-term (HR 1.12, CI 1.00-1.25, p = 0.046). After adjustments, only the three-year association remained significant. In unadjusted analyses, PRA was associated with cardiovascular death, but not with nonfatal cardiovascular events. In the subgroup there was an inverse relation between PRA and long-term all-cause mortality.CONCLUSION: Higher PRA was a significant independent predictor of all-cause mortality after three years, but not at long-term follow-up and not significantly associated with cardiovascular incidence. The renin-angiotensin-system pathophysiology is of great interest, not least due to its association with the COVID-19 pandemic. Our findings indicate a need for further research on the prognostic/predictive aspects of the renin-angiotensin-system in ACS.
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| 2. |
- Hofmann, R., et al.
(författare)
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Routine Oxygen Therapy Does Not Improve Health-Related Quality of Life in Patients With Acute Myocardial Infarction—Insights From the Randomized DETO2X-AMI Trial
- 2021
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Ingår i: Frontiers in Cardiovascular Medicine. - : Frontiers Media S.A.. - 2297-055X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: After decades of ubiquitous oxygen therapy in all patients with acute myocardial infarction (MI), recent guidelines are more restrictive based on lack of efficacy in contemporary trials evaluating hard clinical outcomes in patients without hypoxemia at baseline. However, no evidence regarding treatment effects on health-related quality of life (HRQoL) exists. In this study, we investigated the impact of routine oxygen supplementation on HRQoL 6–8 weeks after hospitalization with acute MI. Secondary objectives included analyses of MI subtypes, further adjustment for infarct size, and oxygen saturation at baseline and 1-year follow-up.Methods: In the DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial, 6,629 normoxemic patients with suspected MI were randomized to oxygen at 6 L/min for 6–12 h or ambient air. In this prespecified analysis, patients younger than 75 years of age with confirmed MI who had available HRQoL data by European Quality of Life Five Dimensions questionnaire (EQ-5D) in the national registry were included. Primary endpoint was the EQ-5D index assessed by multivariate linear regression at 6–10 weeks after MI occurrence.Results: A total of 3,086 patients (median age 64, 22% female) were eligible, 1,518 allocated to oxygen and 1,568 to ambient air. We found no statistically significant effect of oxygen therapy on EQ-5D index (−0.01; 95% CI: −0.03–0.01; p = 0.23) or EQ-VAS score (−0.57; 95% CI: −1.88–0.75; p = 0.40) compared to ambient air after 6–10 weeks. Furthermore, no significant difference was observed between the treatment groups in EQ-5D dimensions. Results remained consistent across MI subtypes and at 1-year follow-up, including further adjustment for infarct size or oxygen saturation at baseline.Conclusions: Routine oxygen therapy provided to normoxemic patients with acute MI did not improve HRQoL up to 1 year after MI occurrence. Clinical Trial Registration: ClinicalTrials.gov number, NCT01787110.
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| 3. |
- Jensen, Gert, 1950, et al.
(författare)
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Survival and quality of life after renal angioplasty: a five-year follow-up study.
- 2009
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 43:3, s. 236-41
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Renal percutaneous transluminal angioplasty (PTA) treatment of renal artery stenosis has been performed worldwide since 1978, but it is still a matter of debate as to what extent the patients benefit from the procedure in terms of quality of life and long-term survival. MATERIAL AND METHODS: Of 139 patients referred for renal angioplasty owing to hypertension or pending uraemia, 105 were subsequently treated with PTA. Eighty-eight patients survived for 5 years. Fifty-nine patients were re-examined according to a protocol including physical examination, blood pressure, drug therapy, glomerular filtration rate and quality of life assessment, and an additional 29 patients were interviewed by telephone regarding quality of life. PTA was not conducted in 34 patients owing to high risks as decided at joint radiology-nephrology conferences. RESULTS: The 5-year survival was 83% for PTA-treated patients with arteriosclerotic renovascular disease, 100% for patients with fibromuscular vascular disease and 47% for the non-PTA-treated patients. The main causes of death were cardiovascular and cerebrovascular events in both groups. Reduced blood pressure and reduced need for antihypertensive drug treatment were observed in the PTA-treated patients. The renal function was stable. A majority of the PTA-treated patients stated that they had "unrestricted" physical activity, and the physical, mental and social well-being was self-rated as level 4-5 (mostly good and very good) on a five-grade scale by 53%, 67% and 75% of the patients, respectively, at the follow-up investigation. The untreated patients were not interviewed. CONCLUSION: The study showed a high survival rate, improved blood pressure control and stable renal function 5 years after renal PTA, and a vast majority of the patients rated their physical, mental and social well-being favourably.
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| 4. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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GH increases extracellular volume by stimulating sodium reabsorption in the distal nephron and preventing pressure natriuresis.
- 2002
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 87:4, s. 1743-9
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Tidskriftsartikel (refereegranskat)abstract
- Although sodium retention and volume expansion occur during GH administration, blood pressure is decreased or unchanged. The aim was to study the effect of short- and long-term GH replacement in adults on sodium balance, renal hemodynamics, and blood pressure. Ten adults with severe GH deficiency were included into a 7-d, randomized, placebo-controlled, cross-over trial followed by 12 months of open GH replacement. All measurements were performed under metabolic ward conditions. Extracellular water (ECW) was determined using multifrequency bioelectrical impedance analysis. Renal plasma flow and glomerular filtration rate were assessed using renal paraminohippurate and Cr(51) EDTA clearances, respectively. Renal tubular sodium reabsorption was assessed using lithium clearance. Plasma renin activity (PRA), plasma concentrations of angiotensin II, aldosterone, atrial natriuretic peptides and brain natriuretic peptides (BNP) and 24-h urinary norepinephrine excretion were measured. Seven days of GH treatment decreased urinary sodium excretion. Lithium clearance as a marker of proximal renal tubular sodium reabsorption was unaffected by GH treatment. ECW was increased after both short- and long-term treatment. This increase was inversely correlated to the decrease in diastolic blood pressure (r = -0.70, P = 0.02) between baseline and 12 months. Short-term treatment increased PRA and decreased BNP. The increase in PRA correlated with an increase in 24-h urinary norepinephrine excretion (r = 0.77, P < 0.01). Glomerular filtration rate and renal plasma flow did not change during treatment. The sodium- and water-retaining effect of GH takes place in the distal nephron. The sustained increase in ECW in response to GH is associated with an unchanged or decreased blood pressure. This together with unchanged or decreased atrial natriuretic peptides and BNP may prevent pressure-induced escape of sodium.
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| 5. |
- Jonsson, Olof, 1941, et al.
(författare)
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Prophylaxis against bone loss in kock reservoir patients with reduced glomerular filtration rate.
- 2005
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Ingår i: Scand J Urol Nephrol. - : Informa UK Limited. ; 39:3, s. 200-205
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Tidskriftsartikel (refereegranskat)abstract
- Objective We investigated whether treatment with calcium carbonate and vitamin D3 can improve the bone mineral content of patients with ileal reservoirs for continent urinary diversion and a reduced glomerular filtration rate (GFR). Material and methods Twenty-six patients with Kock reservoirs were included in the study. Bone mineralization was determined using dual-energy X-ray absorptiometry. Kidney function was estimated from Cr-EDTA clearance and serum cystatin C concentration. Osteocalcin and parathyroid hormone in serum were also measured. Patients with reduced GFR were treated with calcium carbonate and vitamin D3 perorally. Results Bone mineral density in the femur neck and hip increased in the treatment group, as reflected by an improved T score. Conclusion Patients with ileal reservoirs for continent urinary diversion and reduced kidney function should be supplemented with calcium carbonate and vitamin D3 in order to reduce the long-term risk of osteoporosis.
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| 6. |
- Magnusson, Carl, 1976, et al.
(författare)
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The performance of the EMS triage (RETTS-p) and the agreement between the field assessment and final hospital diagnosis: a prospective observational study among children <16years.
- 2019
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Ingår i: BMC pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- The rapid triage and treatment system for paediatrics (RETTS-p) has been used by the emergency medical services (EMS) in the west of Sweden since 2014. The performance of the RETTS-p in the pre-hospital setting and the agreement between the EMS nurse's field assessment and the hospital diagnosis is unknown. The aim of this study was to evaluate the performance of the RETTS-p in the EMS and the agreement between the EMS field assessment and the hospital diagnosis.A prospective observational study was conducted among 454 patients <16years of age who were assessed and transported to the PED. Two instruments were used for comparison: 1) Classification of an emergent patient according to predefined criteria as compared to the RETTS-p and 2) Agreement between the EMS nurse's field assessment and the hospital diagnosis.Among all children, 11% were identified as having vital signs associated with an increased risk of death and 7% were diagnosed in hospital with a potentially life-threatening condition. Of the children triaged with RETTS-p (85.9%), 149 of 390 children (38.2%) were triaged to RETTS-p red or orange (life-threatening, potentially life-threatening), of which 40 (26.8%) children were classified as emergent. The hospitalised children were triaged with the highest frequency to level yellow (can wait; 41.5%). In children with RETTS-p red or orange, the sensitivity for a defined emergent patient was 66.7%, with a corresponding specificity of 67.0%. The EMS field assessment was in agreement with the final hospital diagnosis in 80% of the cases.The RETTS-p sensitivity in this study is considered moderate. Two thirds of the children triaged to life threatening or potentially life threatening were later identified as non-emergent. Of those, one in six was discharged from the PED without any intervention. Further, one third of the children were under triaged, the majority were found in the yellow triage level (can wait). The highest proportion of hospitalised patients was found in the yellow triage level. Our result is in agreement with previous studies using other triage instruments. A computerised decision support system might help the EMS triage to increase sensitivity and specificity.
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| 7. |
- Svensson, Johan, 1964, et al.
(författare)
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Adiponectin, leptin, and erythrocyte sodium/lithium countertransport activity, but not resistin, are related to glucose metabolism in growth hormone-deficient adults.
- 2005
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 90:4, s. 2290-6
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Tidskriftsartikel (refereegranskat)abstract
- In a randomized, placebo-controlled, crossover study under metabolic ward conditions, 10 GH-deficient adults received 1-wk GH replacement therapy (9.5 microg/kg.d). The effect of this treatment on the erythrocyte sodium/lithium countertransport (SLC) activity and on serum levels of adiponectin, resistin, leptin, IGF binding protein-1 (IGFBP-1) and IL-6 was determined. The 1-wk GH replacement impaired glucose homeostasis determined from an oral glucose tolerance test. The other measured variables in serum were unchanged by GH replacement. At baseline, serum adiponectin level was inversely correlated and serum leptin level was positively correlated with measures of glucose tolerance and insulin sensitivity. The changes in serum leptin level and erythrocyte SLC activity were positively correlated, and the change in serum IGFBP-1 level was negatively correlated, correlated with changes in measures of glucose metabolism. In conclusion, short-term GH treatment induced glucose intolerance but did not significantly change the erythrocyte SLC activity and the serum levels of adipokines, arguing against direct effects of GH on these measures. However, baseline values or changes in erythrocyte SLC activity, adiponectin, leptin, and IGFBP-1 correlated with glucose metabolism. This suggests that these factors are of importance for glucose homeostasis in GH-deficient adults, most likely through GH-independent mechanisms.
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| 8. |
- Alhadad, Alaa, et al.
(författare)
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Renal angioplasty causes a rapid transient increase in inflammatory biomarkers, but reduced levels of interleukin-6 and endothelin-1 1 month after intervention.
- 2007
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Ingår i: Journal of hypertension. - 0263-6352 .- 1473-5598. ; 25:9, s. 1907-14
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine prospectively whether inflammatory biomarkers and endothelin (ET)-1 are increased in patients with renal artery stenosis (RAS), and to investigate how treatment with percutaneous transluminal renal angioplasty (PTRA) affects these variables during the first month after intervention. METHODS: One hundred patients with suspected RAS undergoing renal angiography were included. PTRA was performed if the trans-stenotic mean arterial pressure gradient was>or=10 mmHg. High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFalpha), neopterin, CD40 ligand (CD40L) and endothelin-1 (ET-1) were measured before, and 1 day and 1 month after PTRA (n=61) or diagnostic angiography only (n=39). RESULTS: At baseline there were no significant differences in inflammatory biomarkers or ET-1 levels between patients subsequently undergoing PTRA or angiography only. After angiography, IL-6 and hs-CRP had increased in both groups compared to baseline (P<0.001). At this time point hs-CRP (10.90+/-1.48 versus 6.37+/-1.61 mg/l; P<0.05) and IL-6 (13.70+/-0.94 versus 13.00+/-0.17 pg/ml; P<0.01) were higher in the PTRA group than in patients subjected to angiography only. One month after PTRA, systolic blood pressure and levels of IL-6 and ET-1 were lower than before intervention (P<0.05), whereas CD40L had increased compared to baseline (P<0.01). CONCLUSION: In patients with RAS, PTRA triggers rapid transient increases in hs-CRP and IL-6; however, 1 month after PTRA, both IL-6 and ET-1 had decreased compared to before intervention, indicating beneficial effects of PTRA on inflammation and the endothelin system.
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| 9. |
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| 10. |
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| 11. |
- Dahlqvist, Johanna, 1979-, et al.
(författare)
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Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
- 2022
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Ingår i: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
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Tidskriftsartikel (refereegranskat)abstract
- Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
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| 12. |
- Dieckmann, Regis, et al.
(författare)
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Antieosinophil Antibodies Alone or in Combination with Antineutrophil Cytoplasmic Antibodies (ANCA) Detected in Different Autoimmune Conditions
- 2023
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Ingår i: Journal of Immunology Research. - 2314-8861 .- 2314-7156. ; 2023
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Tidskriftsartikel (refereegranskat)abstract
- Circulating antieosinophil antibodies (AEOSA) have been associated with various autoimmune conditions affecting the liver, kidneys, lungs, and joints but are not part of routine clinical diagnostics. While analyzing human sera for antineutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence (IIF) on granulocytes, 0.8% of analyzed samples were found to be reactive with eosinophils. Our aim was to determine the diagnostic relevance and antigenic specificity of AEOSA. AEOSA were seen either in combination with an myeloperoxidase (MPO)-positive p-ANCA (44%; AEOSA+/ANCA+) or on their own (56%; AEOSA+/ANCA-). AEOSA/ANCA positivity was seen in patients with thyroid disease (44%) or vasculitis (31%), while AEOSA+/ANCA- pattern was more common in patients with autoimmune disorders of the gastrointestinal tract and/or liver. Eosinophil peroxidase (EPX) was the main target recognized in 66% of the AEOSA+ sera by enzyme-linked immunosorbent assay (ELISA). Eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) were also identified as target antigens but less frequently and only in combination with EPX. In conclusion, we confirmed that EPX is a major target of AEOSA, illustrating the high antigenic potential of EPX. Our results also demonstrate the presence of concomitant AEOSA/ANCA positivity in a defined patient group. Further research should aim to elucidate the association of AEOSA with autoimmunity.
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| 13. |
- Ekman, Diana, et al.
(författare)
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Stratified genetic analysis reveals sex differences in MPO-ANCA-associated vasculitis
- 2023
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:9, s. 3213-3218
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype. Methods: A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems. Results: rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 × 10-4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619. Conclusions: Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.
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| 14. |
- Elias, Erik, 1979, et al.
(författare)
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Erythrocyte sodium-lithium countertransport activity is inversely correlated to adiponectin, retinol binding protein 4 and body height.
- 2010
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Ingår i: Scandinavian journal of clinical and laboratory investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 70:7, s. 487-91
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Tidskriftsartikel (refereegranskat)abstract
- We have previously described that the sodium/lithium countertransport (SLC) in the erythrocyte cell membrane is closely linked to obesity and insulin resistance. Adiponectin and retinol-binding protein 4 (RBP-4) are believed to affect obesity and insulin resistance. In the present study, we aimed to further characterize the relationship between SLC, inflammatory markers, adiponectin and RBP-4.
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| 15. |
- Fehrman-Ekholm, Ingela, 1947, et al.
(författare)
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Living kidney donors developing end-stage renal disease
- 2006
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Ingår i: Transplantation proceedings. - : Elsevier BV. - 0041-1345. ; 38:8, s. 2642-3
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of end-stage kidney failure (ESRF) was analyzed among the cohort of 1112 living kidney donors who underwent nephrectomy from 1965 through 2005. It was found that at least six persons had developed ESRF at 14 to 27 years (median = 20 years), following donation. Five of six were men. Five were parents and one, a sibling. The diagnoses were nephrosclerosis (n = 4), postrenal failure (n = 1), and renal carcinoma (n = 1). One donor, aged 45 years, underwent kidney transplantation.
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| 16. |
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| 17. |
- Fu, Michael, 1963, et al.
(författare)
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Agonist-like activity of antibodies to angiotensin II receptor subtype 1 (AT1) from rats immunized with AT1 receptor peptide.
- 1999
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Ingår i: Blood pressure. - 0803-7051. ; 8:5-6, s. 317-24
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, rats were immunized with angiotensin II receptor subtype 1 (AT1) receptor peptides for 3 months to see if the immunization produced specific anti-AT1 receptor antibodies and if continuous stimulation for 3 months affected blood pressure or induced morphological changes in the organs containing AT1 receptors. Our results showed that there were constant high levels of circulating antibodies throughout the study period in all rats of the immunized group, but not in the control rats, and that there were almost no significant cross-reactions of antisera with AT2 receptor peptide and alpha1 adrenoceptor peptide, except in four rats, which showed low cross-reactions with alpha1 adrenoceptor and AT2 receptor peptides. When an affinity-purified anti-AT1 receptor antibody was used, it specifically displayed the AT1-stimulatory positive chronotropic effect and also localized AT1 receptors. However, in the immunized group, saturation binding of AT1 in homogenates from kidneys showed no difference either in maximal binding sites (Bmax) or in antagonist affinity (Kd). No difference in mRNA of AT1a was found in either kidney or heart, and no morphological changes in the organs were observed, as compared with the control group. Furthermore, immunization did not cause hypertension. In conclusion, the synthetic peptide corresponding to the second extra-cellular loop of the human AT1 receptor was able to produce highly specific and functionally active anti-AT1 receptor antibodies, but unable to induce pathological structural changes or hypertension.
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| 18. |
- Fu, Michael, 1963, et al.
(författare)
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Autoantibodies against cardiac G-protein-coupled receptors define different populations with cardiomyopathies but not with hypertension.
- 1994
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Ingår i: Clinical immunology and immunopathology. - 0090-1229. ; 72:1, s. 15-20
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Tidskriftsartikel (refereegranskat)abstract
- It was previously shown that the second extracellular loop of cardiovascular G-protein-coupled receptors is an antigenic target for pharmacologically active autoantibodies in patients with idiopathic dilated cardiomyopathy. To extend these observations to cover patients with the same disease from different geographical origins or to patients with other cardiac diseases, peptides corresponding to the sequences of the second extracellular loops of the human M2 muscarinic receptors and beta adrenoceptors were used as antigens in an enzyme immunoassay. Sera from patients from Sweden and Japan with idiopathic dilated cardiomyopathy (DCM, n = 32), hypertrophic cardiomyopathy (HCM, n = 23), malignant essential hypertension (MEH, n = 11), malignant secondary hypertension (MSH, n = 10), and sera from healthy blood donors (HBD, n = 49) were tested. Sera from patients with DCM recognized the muscarinic receptor peptide in 38% of cases and the beta 1 adrenoceptor peptide in 31% of cases. In 50% of the positive patients, autoantibodies against both peptides coexisted as shown by competition experiments using both peptides as inhibitors. In HCM patients, there was a lower frequency of autoantibodies but with a higher but not significant predominance against the M2 peptide. No autoantibodies were detected in sera from patients with MEH or MSH. Autoantibodies against the M2 muscarinic receptors, affinity-purified from positive patients, displayed pharmacological activity as demonstrated by changes in the affinity and number of radioligand binding sites. In contrast, antibodies purified from positive HBD had no effect. These results confirm that autoantibodies displaying pharmacological activity against G-protein-coupled cardiovascular receptors are mainly restricted to patients with idiopathic dilated cardiomyopathy and that different autoantibody populations are responsible for the recognition of the different receptors.
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| 19. |
- Fu, Michael, 1963, et al.
(författare)
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Autoantibodies against the angiotensin receptor (AT1) in patients with hypertension.
- 2000
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Ingår i: Journal of hypertension. - 0263-6352. ; 18:7, s. 945-53
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Tidskriftsartikel (refereegranskat)abstract
- Sera from patients with malignant essential hypertension (n = 14), malignant secondary hypertension mainly attributable to renovascular diseases (n = 12) and renovascular diseases without malignant hypertension (n = 11) and from normotensive healthy blood donors (n = 35) were studied for the presence of autoantibodies against G-protein-coupled cardiovascular receptors. Autoantibodies against the angiotensin II receptor (AT1) were detected in 14, 33, 18 and 14% of patients with malignant essential hypertension, malignant secondary hypertension, renovascular diseases and control patients, respectively. Sensitivity of the enzyme immunoassay was assessed as 5 microg/ml IgG. Patients did not show antibodies against bradykinin (B2) or angiotensin II subtype 2 (AT2) receptors. Autoantibodies affinity-purified from positive patients localized AT receptors in Chinese hamster ovary transfected cells, and displayed a positive chronotropic effect on cultured neonatal rat cardiomyocytes. These results demonstrate the existence of autoantibodies against a functional extracellular domain of human AT1 receptors in patients with malignant hypertension, and suggest that these autoantibodies might be involved in the pathogenesis of malignant hypertension.
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| 20. |
- Fu, Michael, 1963, et al.
(författare)
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Functional autoimmune epitope on alpha 1-adrenergic receptors in patients with malignant hypertension.
- 1994
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Ingår i: Lancet. - 0140-6736. ; 344:8938, s. 1660-3
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Tidskriftsartikel (refereegranskat)abstract
- Because of the growing evidence that hypertensive disease is accompanied by immunological dysfunction, we have investigated autoimmunity in patients with malignant hypertension. Peptides corresponding to the sequence of the second extracellular loops of the human alpha 1-adrenergic receptor and the M2-muscarinic receptor were used as antigens in an ELISA. Serum from 4 (12%) of 33 healthy controls, 3 (20%) of 15 patients with malignant essential hypertension, and 7 (64%) of 11 with secondary hypertension showed positive responses in the ELISA for the alpha 1-adrenergic receptor peptide. Positive responses were significantly more common among the patients with secondary hypertension than in the other two groups (p < 0.01). By contrast, no autoantibodies against the M2-muscarinic receptor peptide were detected in either hypertensive group. Autoantibodies against the alpha 1-adrenergic receptor, affinity-purified from patients with positive responses, specifically recognised bands with molecular masses of 68, 40, and 37 kDa on immunoblotted membrane proteins of rat ventricles. The patients' autoantibodies caused a decrease in tritiated prazosin binding sites and an increase in heart beating frequency of neonatal cultured rat cardiomyocytes; antibodies purified from the controls had no effect. Circulating autoantibodies against the alpha 1-adrenergic receptor are present in a subgroup of patients with malignant hypertension. These autoantibodies have pharmacological activity in vitro, which suggests that they may be involved in the pathogenesis of malignant hypertension.
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| 21. |
- Galle, Jan-Christoph, et al.
(författare)
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An observational cohort study of extended dosing (once every 2 weeks or once monthly) regimens with darbepoetin alfa in patients with chronic kidney disease not on dialysis: the EXTEND study.
- 2012
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Ingår i: Nephrology, dialysis, transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 27:6, s. 2303-2311
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Darbepoetin alfa (DA) has been shown to be an effective treatment of anaemia in patients with chronic kidney disease (CKD) not on dialysis (NoD). EXTEND is an observational study assessing the effectiveness of DA administered once biweekly (Q2W) or monthly (QM) in a general CKD-NoD population.METHODS: Adult CKD-NoD patients starting DA Q2W/QM treatment in June 2006 or later were eligible. Retrospective and/or prospective data including haemoglobin levels and erythropoiesis-stimulating agent (ESA) dosing were collected for 6 months before and 12 months after DA initiation. Mean Hb levels were calculated every 3 months, and ESA dose was converted to a geometric mean weekly DA equivalent dose and summarized monthly.RESULTS: Data from 4278 patients showed that patients receiving ESA treatment before DA Q2W/QM initiation had a mean (95% confidence interval) Hb level of 11.9 g/dL (11.8-12.0 g/dL) at initiation and 11.6 g/dL (11.6-11.7 g/dL) at Months 10-12, with mean ESA dose of 22 μg/week (21-23 μg/week) prior to initiation, 16 μg/week (15-16 μg/week) at initiation and 16 μg/week (15-16 μg/week) at Month 12. In ESA-naive patients, Hb levels increased from 10.3 g/dL (10.2-10.3 g/dL) at initiation to 11.7 g/dL at Months 4-6 and were maintained at a mean level of 11.7 g/dL (11.7-11.8 g/dL) at Months 10-12, with mean ESA dose of 16 μg/week (16-17 μg/week) at initiation and 16 μg/week (16-17 μg/week) at Month 12. In the 85% of patients receiving DA at extended intervals (Q2W or less frequently) at Month 12, 12 patients (0.3%) experienced DA-related adverse reactions.CONCLUSION: DA Q2W/QM was an effective treatment of anaemia in the general CKD-NoD patient population and a dose increase was not required in patients switching from a previous ESA regimen.
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| 22. |
- Galle, J. C., et al.
(författare)
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Outcomes in patients with chronic kidney disease not on dialysis receiving extended dosing regimens of darbepoetin alfa: long-term results of the EXTEND observational cohort study
- 2016
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 31:12, s. 2073-2085
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Tidskriftsartikel (refereegranskat)abstract
- Background. Extended dosing of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa (DA) once biweekly or monthly reduces anaemia treatment burden. This observational study assessed outcomes and dosing patterns in patients with chronic kidney disease not on dialysis (CKD-NoD) commencing extended dosing of DA. Methods. Adult CKD-NoD patients starting extended dosing of DA in Europe or Australia in June 2006 or later were followed up until December 2012. Outcomes included haemoglobin (Hb) concentration, ESA dosing, mortality rates and receipt of dialysis and renal transplantation. Subgroup analyses were conducted for selected outcomes. Results. Of 6035 enrolled subjects, 5723 (94.8%) met analysis criteria; 1795 (29.7%) received dialysis and 238 (3.9%) underwent renal transplantation. Mean (standard deviation) Hb concentration at commencement of extended dosing was 11.0 (1.5) g/dL. Mean [95% confidence interval (CI)] Hb 12 months after commencement of extended dosing (primary outcome) was 11.6 g/dL (11.5, 11.6) overall and was similar across countries, with no differences between subjects previously treated with an ESA versus ESA-naive subjects, subjects with versus without prior renal transplant or diabetics versus non-diabetics. Weekly ESA dose gradually decreased following commencement of extended DA dosing and was similar across subgroups. The decrease in weekly DA dose was accompanied by an increase in the proportion of patients receiving iron therapy. Hb concentrations declined following changes in ESA labels and treatment guidelines. The mortality rate (95% CI) was 7.06 (6.68, 7.46) deaths per 100 years of follow-up. Subjects alive at study end had stable Hb concentrations in the preceding year, while those who died had lower and declining Hb concentrations in their last year. Conclusions. Long-term, extended dosing of DA maintained Hb concentrations in patients already treated with an ESA and corrected and maintained Hb in ESA-naive patients.
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| 23. |
- Guron, Gregor, 1967, et al.
(författare)
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Acute effects of the superoxide dismutase mimetic tempol on split kidney function in two-kidney one-clip hypertensive rats.
- 2006
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Ingår i: Journal of hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352. ; 24:2, s. 387-94
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the acute effects of the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol) on split kidney function, and renal haemodynamics, in two-kidney, one-clip (2K1C) hypertensive rats. METHODS: Three weeks after clipping, or the sham procedure, the effects of intravenous tempol (200 micromol/kg per h) were evaluated on thiobutabarbital anaesthetized Sprague-Dawley rats. RESULTS: Mean arterial pressure (MAP; 152 +/- 3 versus 122 +/- 3 mmHg, P < 0.001), plasma renin activity (28.7 +/- 3.0 versus 9.5 +/- 0.6 ng/ml per h, P < 0.001) and urinary 8-iso-prostaglandin F2alpha excretion (124 +/- 4 versus 92 +/- 10 pmol/24 h, P = 0.003) were significantly elevated in 2K1C rats compared with sham. Tempol reduced MAP by 15 +/- 1% compared with baseline (P < 0.001) in 2K1C rats. In clipped kidneys, tempol increased the glomerular filtration rate (GFR; +50 +/- 15% from baseline) and the effective renal plasma flow (ERPF; +37 +/- 13%, from baseline), and reduced renal vascular resistance (RVR; -32 +/- 6% from baseline) compared with saline-treated controls (P < 0.05). In non-clipped kidneys, tempol reduced RVR (-24 +/- 5% from baseline) compared with saline-treated controls (P = 0.001). In sham-operated rats, tempol produced a modest reduction in MAP (-8 +/- 2% from baseline, P = 0.003), but did not significantly affect renal haemodynamics or function. CONCLUSION: Tempol reduced MAP and RVR in both clipped and non-clipped kidneys of 2K1C hypertensive rats. In addition, tempol increased ERPF and GFR in the clipped kidney. These findings suggest important roles for superoxide in the regulation of renal haemodynamics during the early maintenance phase of renovascular hypertension.
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| 24. |
- Herlitz, Hans, 1946, et al.
(författare)
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Albuminuria within the normal range and ultrasound assessed atherosclerosis in the AIR study – a 9-year follow-up of 58-year old clinically healthy men : Normoalbuminuria and intima media thickness
- 2009
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 69:4, s. 512-517
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Tidskriftsartikel (refereegranskat)abstract
- Background:Microalbuminuria, traditionally defined as 30–300 mg urinary albumin/24 h, predicts renal impairment and cardiovascular disease. Studies suggest that also a far lower urinary albumin excretion (UAE) can predict clinical outcome. Intima media thickness (IMT) is an established estimate of atherosclerosis. In this study, we investigated the predictive value of UAE within the normal rate (UAE–n) for the progression of IMT in the carotid and femoral arteries. Methods: We included 325 clinically healthy men with normoalbuminuria. Anthropometrics, urine and blood samples were taken and IMT in the carotid and femoral arteries were assessed by B–mode ultrasound at baseline and after 3 and 9 years. The annual progression rate of IMT (r–IMT) was calculated. Results: UAE–n correlated with carotid IMT at baseline and after 3 and 9 years, but not with r–IMT. In a regression analysis, only HDL and baseline IMT remained as statistically significant co–variates to mean IMT at 9 years. IMT in the femoral artery and r–IMT at any time–point did not correlate to baseline UAE. Conclusion: UAE–n was associated with carotid IMT after 3 and 9 years but not r–IMT or with femoral artery IMT. Carotid IMT after 9 years' follow–up was independently related to baseline IMT and HDL cholesterol. In this cohort of 58–year–old men, our interpretation is that UAE–n is not associated with the increase in carotid and femoral artery IMT observed after 9 years
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| 25. |
- Herlitz, Hans, 1946, et al.
(författare)
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Erythrocyte sodium/lithium countertransport is associated with thrombotic and fibrinolytic factors in 58-year-old men
- 2004
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Ingår i: Thromb Haemost. - 0340-6245. ; 91:6, s. 1152-7
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Tidskriftsartikel (refereegranskat)abstract
- The metabolic syndrome, in which insulin resistance is the core feature, is associated both with dysregulation of thrombosis/fibrinolysis and erythrocyte sodium/lithium countertransport (SLC). To investigate this further we designed a cross-sectional study to examine whether factors involved in coagulation- and fibrinolysis systems were associated with SLC independently of insulin resistance in 93 58-year-old men. SLC was in univariate analysis positively correlated with PAI-1 activity (r = 0.35, p <0.01), tPA antigen (r = 0.38, p <0.01), von Willebrand factor (r = 0.25, p <0.05), protein S (r = 0.26, p <0.05), and C (r = 0.30, p <0.01), and negatively associated with tPA activity(r = -0.28, p <0.01). Since these correlations could be influenced by the components of the metabolic syndrome itself, a separate analysis with adjustment for glucose infusion rate (GIR), plasma insulin, body fat, sagittal diameter of the abdomen (SD) and log serum triglyceride concentration (TG) was conducted. Then SLC was associated with tPA antigen independent of GIR, plasma insulin, body fat, SD and TG. SLC was also associated with protein C independent of GIR, insulin, body fat and SD but not TG. In conclusion, we found a relationship between SLC and the fibrinolytic system that was not related to the metabolic syndrome.
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| 26. |
- Herlitz, Hans, 1946, et al.
(författare)
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Failure of angiotensin II to suppress plasma renin activity in normotensive subjects with a positive family history of hypertension.
- 2005
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Ingår i: Clinical science (London, England : 1979). - 0143-5221. ; 109:3, s. 311-7
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Tidskriftsartikel (refereegranskat)abstract
- The renin-angiotensin system is implicated in the pathophysiology of hypertension. Renin release is regulated by a number of factors, including circulating Ang II (angiotensin II), the so-called short feedback loop. The aim of the present study was to investigate the responsiveness of circulating Ang II on PRA (plasma renin activity) in normotensive subjects with a PFH or NFH (positive or negative family history of hypertension respectively). PRA, renal haemodynamics and urinary sodium excretion were measured during infusion of Ang II without and with pretreatment with the AT1 (Ang II type 1) receptor blocker irbesartan. Normotensive men with a PFH (n=13) and NFH (n=10), with a mean age of 38 years, were given on different occasions intravenous Ang II infusions of 0.1, 0.5 and 1.0 ng.kg-1 of body weight.min-1 before and after pretreatment with 150 mg of irbesartan once a day for 5 consecutive days. RPF (renal plasma flow) and GFR (glomerular filtration rate) were also measured. Before Ang II infusion, the PFH and NFH groups did not differ with respect to BP (blood pressure), body mass index, PRA, RBF (renal blood flow) or urinary sodium. There was no difference in BP or renal haemodynamic response to the highest Ang II dose between the groups. PRA declined with the highest Ang II dose (P<0.01) in subjects with a NFH, but not in subjects with a PFH. After treatment with irbesartan when Ang II had no effect on BP in either group, Ang II also suppressed PRA in subjects with a PFH (P<0.01), and the difference between the groups at baseline was thus eliminated. In conclusion, these findings indicate that subjects with a PFH have a defective Ang II suppression of PRA, which is corrected by AT1 receptor blockade.
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| 27. |
- Jansson, Svante, 1948, et al.
(författare)
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Quiz page June 2015: a young woman with hypertension.
- 2015
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Ingår i: American journal of kidney diseases : the official journal of the National Kidney Foundation. - : Elsevier BV. - 1523-6838. ; 65:6
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Tidskriftsartikel (refereegranskat)
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| 28. |
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| 29. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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Anemia is associated with increased risk of non-vertebral osteoporotic fractures in elderly men: the MrOS Sweden cohort
- 2022
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Ingår i: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- This study includes 1005 men from the Gothenburg part of the Osteoporotic Fracture in Men Study (MrOS). Included are 66 men with anemia (hemoglobin < 130 g/L). The follow-up time was up to 16 years, and the main results are that anemia is associated with all fractures and non-vertebral osteoporotic fractures. Introduction Anemia and osteoporotic fractures are conditions that are associated with increased morbidity and mortality. Clinical studies have suggested that anemia can be used as a predictor of future osteoporotic fractures. Method Men from the Osteoporotic Fractures in Men Study (MrOS) Sweden, Gothenburg, with available hemoglobin (Hb) values (n = 1005, median age 75.3 years (SD 3.2)), were included in the current analyses. Of these, 66 suffered from anemia, defined as Hb < 130 g/L. Median follow-up time for fracture was 10.1 years and the longest follow-up time was 16.1 years. Results Men with anemia had, at baseline, experienced more falls and had a higher prevalence of diabetes, cancer, prostate cancer, hypertension, and stroke. Anemia was not statistically significantly associated with bone mineral density (BMD). Men with anemia had higher serum levels of fibroblast growth factor 23 (iFGF23) (p < 0.001) and phosphate (p = 0.001) and lower serum levels of testosterone (p < 0.001) and estradiol (p < 0.001). Moreover, men with anemia had an increased risk of any fracture (hazard ratio (HR) 1.97, 95% CI 1.28-3.02) and non-vertebral osteoporotic fracture (HR 2.15, 95% CI 1.18-3.93), after adjustment for age and total hip BMD, in 10 years. The risk for any fracture was increased in 10 and 16 years independently of falls, comorbidities, inflammation, and sex hormones. The age-adjusted risk of hip fracture was increased in men with anemia (HR 2.32, 95% CI 1.06-5.12), in 10 years, although this was no longer statistically significant after further adjustment for total hip BMD. Conclusions Anemia is associated with an increased risk for any fracture and non-vertebral osteoporotic fracture in elderly men with a long follow-up time. The cause is probably multifactorial and our results support that anemia can be used as a predictor for future fracture.
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| 30. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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High platelet count is associated with low bone mineral density: The MrOS Sweden cohort.
- 2021
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 32:5, s. 865-871
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Tidskriftsartikel (refereegranskat)abstract
- In elderly ambulatory men, high platelet and high neutrophil counts are related to low bone mineral density (BMD), after adjustment for relevant covariates. Low hemoglobin (hgb) is even associated with low BMD, but this relationship seems to be dependent on estradiol and osteocalcin.Blood and bone cells exist in close proximity to each other in the bone marrow. Accumulating evidence, from both preclinical and clinical studies, indicates that these cell types are interconnected. Our hypothesis was that BMD measurements are associated with blood count variables and bone remodeling markers.We analyzed blood count variables, bone remodeling markers, and BMD, in subjects from the MrOS cohort from Gothenburg, Sweden. Men with at least one blood count variable (hgb, white blood cell count, or platelet count) analyzed were included in the current analysis (n=1005), median age 75.3years (range 69-81years).Our results show that high platelet counts were related to low BMD at all sites (total hip BMD; r=-0.11, P=0.003). No statistically significant association was seen between platelet counts and bone remodeling markers. Neutrophil counts were negatively associated with total body BMD (r=-0.09, P=0.006) and total hip BMD (r=-0.08, P=0.010), and positively related to serum ALP (r=0.15, P<0.001). Hgb was positively related to total hip BMD (r=0.16, P<0.001), and negatively to serum osteocalcin (r=-0.13, P<0.001). The association between platelet and neutrophil counts and total hip BMD was statistically significant after adjustments for other covariates, but the association between hgb and total hip BMD was dependent on estradiol and osteocalcin.Our observations support the hypothesis of an interplay between blood and bone components.
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| 31. |
- Lewerin, Catharina, 1961, et al.
(författare)
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Low serum iron is associated with high serum intact FGF23 in elderly men: The Swedish MrOS study
- 2017
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 98, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fibroblast growth factor (FGF23) is a protein that is produced by osteoblasts and osteocytes. Increased serum levels of FGF23 have been associated with increased risks of osteoporotic fractures and cardiovascular disease, particularly in participants with poor renal function. Serum iron (Fe) has been suggested as a regulator of FGF23 homeostasis. Objective: To determine whether Fe and iron status are determinants of the levels of intact FGF23 (iFGF23) in elderly men. Methods: The MrOS study is a population-based study of elderly men (N = 1010; mean age, 75.3 years; range, 69-81 years). The levels of Fe, transferrin saturation (TS), and ferritin were evaluated in relation to the serum concentrations of iFGF23 before and after adjustments for confounders. Results: TS<15% was found in 3.5% (34/977) of the participants, who had a higher median level iFGF23 compared with the remaining subjects (47.4 mu rnol/L vs. 41.9 mu mol/L, p = 0.008). The levels of iFGF23 correlated negatively (un-adjusted) with the levels of Fe (r = -0.17, p < 0.001), TS (r = -0.16, p < 0.001) and serum ferritin (r = -0.07, p = 0.022). In addition, in participants with estimated glomerular filtration rate eGFRCystatin C > 60 mL/min, the levels of iFGF23 correlated (age-adjusted) negatively with the levels of Fe (r = -0.15, p < 0.001) and TS (r = -0.17, p < 0.001). The level of iFGF23 correlated positively (un-adjusted) with lumbar spine bone mineral density (BMD) (r = 0.14, p < 0.001), total body BMD (r = 0.11, p = 0.001), and total hip BMD (r = 0.09, p = 0.004). The corresponding correlations, when adjusted for age, weight, and height were: r = 0.08, p = 0.018; r = 0.05, p = 0.120; and r = 0.02, p = 0.624, respectively. No associations were found between BMD and the levels of Fe or TS. Multiple step-wise linear regression analyses [adjusting for age, body mass index (BMI), comorbidity index, cystatin C, C-reactive protein (hs-CRP), serum vitamin D 25-OH (25OHD), phosphate, calcium, parathyroid hormone (PTH), erythropoietin, hemoglobin, lumbar spine BMD, apolipoprotein B/A1 ratio] were performed in three separate models with Fe, TS or ferritin as potential explanatory variables. Fe and TS, but not ferritin, were independent predictors of iFGF23 level (standardized beta-values: -0.10, p <0.001; 0.10, p <0.001; and -0.05, p = 0.062, respectively). Conclusion: Low levels of Fe in elderly men are associated with high levels of iFGF23, independently of markers of inflammation and renal function, suggesting an iron-related pathway for FGF23 regulation. (C) 2017 Elsevier Inc. All rights reserved.
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| 32. |
- Nitescu, Nicoletta, 1974, et al.
(författare)
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Endothelin b receptors preserve renal blood flow in a normotensive model of endotoxin-induced acute kidney dysfunction
- 2008
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Ingår i: Shock. - : Ovid Technologies (Wolters Kluwer Health). - 1073-2322. ; 29:3, s. 402-409
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate the role of endothelin 1 receptor subtypes in the early renal response to lipopolysaccharide (LPS) during normotensive endotoxemia with acute kidney dysfunction. Endotoxemia was induced in thiobutabarbital-anesthetized rats (n = 9 per group) by infusion of LPS (dosage, 1 mg/kg per hour i.v.). The study groups (1) sham-saline, (2) LPS-saline, (3) LPS-BQ123, (4) LPS-BQ788 and (5) LPS-BQ123 + BQ788 received isotonic saline, the ETA receptor antagonist BQ-123 (dosage, 30 nmol/kg per minute i.v.), and/or the ETB receptor antagonist BQ-788 (dosage, 30 nmol/kg per minute i.v.) before and during 2 h of LPS infusion. Renal clearance measurements, renal blood flow (RBF), and cortical and outer medullary perfusion (laser-Doppler flowmetry) and oxygen tension (Clark-type microelectrodes) were analyzed throughout. Before LPS administration, there were no significant differences between groups in glomerular filtration rate (GFR), RBF, or in cortical (CLDF) and outer medullary perfusion. However, mean arterial pressure (MAP) was elevated in LPS-BQ788 group compared with LPS-BQ123 + BQ788 group (P < 0.05). In saline-treated rats, endotoxin induced an approximate 35% reduction in GFR (P < 0.05), without significant effects on MAP, RBF, or on CLDF and cortical PO2. In addition, LPS increased outer medullary perfusion and PO2 (P < 0.05). The fractional urinary excretion rates of sodium, potassium, and water were not significantly different in LPS-saline group compared with sham-saline group. Neither selective nor combined ETA and ETB receptor blockade improved GFR. In BQ-788-infused rats, endotoxin produced marked reductions in RBF (-18% +/- 4% [P < 0.05]) and CLDF (-18% +/- 2% [P < 0.05]). Similarly, endotoxin decreased RBF (-14% +/- 3% [P < 0.05]) and CLDF (-10% +/- 2% [P < 0.05]) in LPS-BQ123 + BQ788 group. Endotoxin reduced MAP (-22% +/- 4% [P < 0.05]) in BQ-123-treated rats but did not significantly influence MAP in other groups. We conclude that in early normotensive endotoxemia, ETB receptors exert a renal vasodilator influence and contribute to maintain normal RBF.
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| 33. |
- Nitescu, Nicoletta, 1974, et al.
(författare)
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Role of endothelin ET(A) and ET(B) receptor subtypes in the regulation of intrarenal blood flow and oxygen tension in rats
- 2008
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Ingår i: Clinical and experimental pharmacology & physiology. - : Wiley. - 1440-1681 .- 0305-1870. ; 35:10, s. 1227-32
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Tidskriftsartikel (refereegranskat)abstract
- 1. The aim of the present study was to investigate the role of endothelin ET(A) and ET(B) receptors in the regulation of intrarenal blood flow and oxygen tension in normotensive Sprague-Dawley rats. 2. Thiobutabarbital anaesthetized rats were divided into four groups (n = 6-9 per group): (i) saline (4 mL/kg per h); (ii) BQ123; (iii) BQ788; and (iv) BQ123 + BQ788. After baseline measurements, the ET(A) receptor antagonist BQ-123 (30 nmol/kg per min, i.v.) and/or the ET(B) receptor antagonist BQ-788 (30 nmol/kg per min, i.v.), was administered for a period of 60 min. Total renal blood flow (RBF), cortical and outer medullary perfusion (laser-Doppler flowmetry) and Po(2) (Clark-type microelectrodes) were analysed throughout. 3. At baseline, there were no significant differences between groups in mean arterial pressure (MAP), RBF, cortical and outer medullary perfusion and Po(2). Infusion of BQ-788 reduced RBF, cortical perfusion and outer medullary Po(2) (P < 0.05) and increased renal vascular resistance (P < 0.05) compared with saline-treated and BQ123 + BQ788-infused groups. BQ-123 and coinfusion of BQ-123 + BQ-788 increased outer medullary perfusion compared with the saline-treated group (P < 0.05) without significantly affecting outer medullary Po(2) and MAP. Neither selective nor combined ET(A) and ET(B) receptor antagonism significantly affected renal cortical Po(2). 4. In conclusion, in normotensive rats, ET(B) receptor antagonism caused renal vasoconstriction and reduced RBF and cortical perfusion. Furthermore, ET(B) receptor antagonism decreased outer medullary Po(2). These effects were mediated by ET(A) receptor activation and are not due to a lack of ET(B) receptor activation per se. Finally, BQ-123 increased renal outer medullary perfusion, suggesting a tonic vasoconstrictor effect of ET(A) receptors in the medulla of normotensive rats.
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| 34. |
- Nowakowska-Fortuna, Elzbieta, et al.
(författare)
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Brain natriuretic peptides in atherosclerotic renal artery stenosis and effects of renal angioplasty
- 2013
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Ingår i: Kidney and Blood Pressure Research. - : S. Karger AG. - 1420-4096 .- 1423-0143. ; 37:6, s. 657-66
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Tidskriftsartikel (refereegranskat)abstract
- Background: We hypothesized that plasma levels of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) would be elevated, and adiponectin concentrations reduced, in patients with atherosclerotic renal artery stenosis (ARAS) and that BNPs might be used to identify patients who would benefit from percutaneous transluminal renal angioplasty (PTRA). Methods: Data were collected before renal angiography in 91 patients with hypertension and suspected ARAS (significant ARAS; n=47, and non-RAS; n=44) and in 20 healthy controls (C). In ARAS patients analyses were repeated four weeks after PTRA. Results: Ambulatory systolic blood pressure (ASBP) was significantly elevated in the ARAS group vs. both C and non-RAS groups. Baseline plasma BNP and NT-proBNP levels were significantly elevated, and adiponectin concentrations reduced, in the ARAS group vs. C but not vs. the non-RAS group. One month after PTRA, ASBP was reduced vs. baseline (149+/-16 to 139+/-15 mm p<0.01). Brain natriuretic peptides were not significantly affected by PTRA. Conclusions: Patients with ARAS showed elevated of BNP and NT-proBNP concentrations, and reduced levels of adiponectin, compared to healthy controls but not vs. hypertensive individuals without RAS. Our data do no support the use of BNP analyses in the identification of ARAS patients who will have a beneficial blood pressure response to PTRA. (c) 2014 S. Karger AG, Basel.
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| 35. |
- Nowakowska-Fortuna, Elzbieta, et al.
(författare)
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Lipoprotein abnormalities in patients with atherosclerotic renovascular disease.
- 2011
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Ingår i: Kidney & blood pressure research. - : S. Karger AG. - 1423-0143 .- 1420-4096. ; 34:5, s. 311-9
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Tidskriftsartikel (refereegranskat)abstract
- Patients with atherosclerotic renovascular disease (ARVD) have a high risk of cardiovascular death. The primary aim was to characterize abnormalities in apolipoprotein (Apo)-defined lipoprotein (Lp) subclasses in patients with ARVD.
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| 36. |
- Saeed, Aso, 1971, et al.
(författare)
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Accuracy of colour duplex sonography for the diagnosis of renal artery stenosis.
- 2009
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Ingår i: Journal of hypertension. - 1473-5598. ; 27:8, s. 1690-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the diagnostic value of novel velocimetric colour duplex sonography indices in the screening of renal artery stenosis (RAS). METHODS: We performed a retrospective analysis of all consecutively studied patients at our centre with suspected RAS, and a colour duplex sonography carried out at less than 4 months (mean 34 days) before renal angiography during a 6-year period (2002-2007). A significant RAS was defined as an at least 60% stenosis on angiography or a transstenotic mean arterial pressure gradient of at least 10 mmHg or both. RESULTS: In a total of 169 patients, 111 stenotic and 206 nonstenotic kidneys were examined. The sensitivity and specificity for acceleration of blood flow in early systole (ACCmax) were 85 and 75%, respectively, and for the acceleration index (ACCmax/peak systolic velocity, AImax) 83 and 79%, respectively. Corresponding values in patients with estimated glomerular filtration rate of less than 30 ml/min/1.73 m2 were 90 and 73% (for ACCmax) and 74 and 88% (for AImax). In addition, the transstenotic mean arterial pressure gradient showed a significant, though weak, negative correlation to ACCmax (r = -0.26, P = 0.02) and AImax (r = -0.29, P = 0.01) in stenotic kidneys. CONCLUSION: ACCmax and AImax provide similar, good diagnostic accuracy in the detection of a haemodynamically significant RAS, even in patients with markedly reduced glomerular filtration rate. Presumably, the lack of superiority of the novel index AImax could be explained by a highly homogenous methodological approach in the present single-centre study.
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| 37. |
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| 38. |
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| 39. |
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| 40. |
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| 41. |
- Sigurjónsdóttir, Helga A, 1964, et al.
(författare)
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Unilateral adrenal hyperplasia is a usual cause of primary hyperaldosteronism. Results from a Swedish screening study.
- 2012
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Ingår i: BMC endocrine disorders. - : Springer Science and Business Media LLC. - 1472-6823. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: The existence of unilateral adrenal hyperplasia (AH) has been considered a rare cause of primary hyperaldosteronism (PA). METHODS: In a prospective study we screened for PA in a non-selected (NSP) and selected hypertensive population (SP), to define the cause of PA. We included 353 consecutive patients with hypertension; age 20 to 88 years, 165 women and 188 men, from a university-based Hypertension and Nephrology Outpatient clinics (123 SP) and two primary care centres, (230 NSP) from the same catch-up area. Serum aldosterone and plasma renin activity (PRA) were measured and the ARR calculated. Verifying diagnostic procedure was performed in patients with both elevated aldosterone and ARR. Patients diagnosed with PA were invited for adrenal venous sampling (AVS) and offered laparoscopic adrenalectomy when AVS found the disease to be unilateral. RESULTS: After screening, 46 patients, 13% of the whole population (22.8% SP and 7.8% NSP) had aldosterone and ARR above the locally defined cut-off limits (0.43 nmol/l and 1.28 respectively). After diagnostic verification, 20 patients (6%) had PA, (14.5% SP and 1.4% NSP). Imaging diagnostic procedures with CT-scans and scintigraphy were inconclusive. AVS, performed in 15 patients verified bilateral disease in 4 and unilateral in 10 patients. One AVS failed. After laparoscopic adrenalectomy, 4 patients were found to have adenoma and 5 unilateral AH. One patient denied operation. CONCLUSION: The prevalence of PA was in agreement with previous studies. The study finds unilateral PA common and unilateral AH as half of those cases. As may be suspected PA is found in much higher frequency in specialised hypertensive units compared to primary care centers. AVS was mandatory in diagnosis of unilateral PA.
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| 42. |
- Svensson, Johan, 1964, et al.
(författare)
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Higher serum free thyroxine levels are associated with increased risk of hip fractures in older men.
- 2024
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Ingår i: Journal of Bone and Mineral Research. - 0884-0431. ; 39:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- Overt and subclinical hyperthyroidism are associated with an increased fracture risk, but whether thyroid hormones are associated with fracture risk in individuals with normal thyroid-stimulating hormone (TSH) has mostly been investigated in women. Therefore, we investigated if serum levels of free thyroxine (FT4) or TSH are associated with fracture risk in Swedish men. We followed (median 12.2yr) elderly men (n=1825; mean age 75, range 69-81yr) participating in the Gothenburg and Malmö subcohorts of the prospective, population-based MrOS-Sweden study. The statistical analyses included Cox proportional hazards regression. Men receiving levothyroxine treatment were excluded. In our total cohort, serum FT4 (per SD increase) was associated with increased risk of major osteoporotic fractures (MOFs; n=479; fully adjusted hazard ratio [HR] 1.14, 95% CI, 1.05-1.24) and hip fractures (n=207; HR 1.18, 95% CI, 1.04-1.33). Also, in men with normal TSH (n=1658), FT4 (per SD increase) was significantly associated with increased risk of MOF and hip fractures. Furthermore, men in the highest FT4 quartile had a 1.5-fold increase in hip fracture risk compared with men in the three lower FT4 quartiles, both in the total population and in men with normal TSH (fully adjusted: HR 1.45, 95% CI, 1.04-2.02 and HR 1.51, 95% CI, 1.07-2.12, respectively). In contrast, the risk of MOF was not statistically different in the highest FT4 quartile compared with the three lower FT4 quartiles. Finally, serum TSH was not associated with fracture risk after full adjustment for covariates. In conclusion, serum FT4, but not serum TSH, is a predictor of hip fracture risk in elderly Swedish men. Additionally, there was an association between FT4 (per SD increase) and the risk of MOF.
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| 43. |
- Sverrisdóttir, Yrsa Bergmann, 1960, et al.
(författare)
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Intense sympathetic nerve activity in adults with hypopituitarism and untreated growth hormone deficiency.
- 1998
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 83:6, s. 1881-5
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Tidskriftsartikel (refereegranskat)abstract
- Perturbations in the sympathetic nervous system may be anticipated in adults with hypopituitarism and untreated GH deficiency, because the syndrome is associated with both peripheral and central factors known to modulate sympathetic traffic. The higher prevalence of hypertension and increased cardiovascular morbidity/mortality reported in GH-deficient patients may suggest increased activity of the sympathetic nervous system. We recorded muscle sympathetic nerve activity (MSNA) in 10 hypopituitary adults with adequate hormonal replacement therapy except GH and in 10 healthy controls matched for age, gender, and body mass index to test whether hormonal aberrations in hypopituitarism and untreated GH deficiency are associated with an increase in sympathetic nerve traffic. Blood samples for insulin-like growth factor I, free T4, and TSH were taken after an overnight fast, followed by an oral glucose tolerance test. Direct intraneural recordings of MSNA were performed with a tungsten microelectrode from the peroneal nerve. The hypopituitary subjects had markedly increased MSNA (54 +/- 4 bursts/min vs. 34 +/- 4 in controls; P < 0.002), which was not related to abdominal obesity or altered glucose metabolism. When assessed for the whole study group, MSNA was inversely correlated to serum insulin-like growth factor I (r = -0.59; P < 0.006) and TSH (r = -0.46; P < 0.04). MSNA was positively correlated to diastolic blood pressure (r = 0.80; P < 0.0005) in patients, but not in controls. The intense sympathetic discharge is suggested to be of central origin and may be an important underlying mechanism for the secondary hypertension and increased cardiovascular morbidity/mortality in this patient group.
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| 44. |
- Sverrisdóttir, Yrsa Bergmann, 1960, et al.
(författare)
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The effect of growth hormone (GH) replacement therapy on sympathetic nerve hyperactivity in hypopituitary adults: a double-blind, placebo-controlled, crossover, short-term trial followed by long-term open GH replacement in hypopituitary adults.
- 2003
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Ingår i: Journal of hypertension. - 0263-6352. ; 21:10, s. 1905-14
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Tidskriftsartikel (refereegranskat)abstract
- To test whether sympathetic nerve hyperactivity associated with adult hypopituitarism and untreated growth hormone (GH) deficiency is affected by GH treatment.Sympathetic nerve activity to the muscle vascular bed (MSA) expressed as burst frequency (bursts/min) and incidence (bursts/100 heartbeats) was recorded in 10 hypopituitary patients (aged 48-69 years), before and after acute (1 week) randomized, double-blind, crossover treatment with a 1-month washout period and chronic (1 year) GH replacement treatment.MSA burst frequency and incidence remained unchanged from baseline values after the short-term treatment, but exhibited decreases in median values [from 53 to 47 bursts/min (P = 0.02) and from 85 to 70 bursts/100 heartbeats (P = 0.03), respectively] after 12 months of replacement therapy. Twenty-four-hour urinary excretion of nitrate increased after the short-term cross-over treatment and the long-term treatment (P = 0.04). Diastolic blood pressure and waist circumference decreased after the 12-month treatment (P = 0.02 and P = 0.04, respectively). No correlation was found between the reduction in MSA and the increase in 24-h urinary nitrate excretion, the decrease in diastolic blood pressure and waist circumference.The sympathoexcitation in adult GH deficiency and the modest decline in MSA seen after long-term GH replacement treatment may suggest that the somatotropic axis is involved in the regulation of central sympathetic outflow.
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| 45. |
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| 46. |
- Zachrisson, Karin, et al.
(författare)
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Long-term outcome of stenting for atherosclerotic renal artery stenosis and the effect of angiographic restenosis.
- 2018
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Ingår i: Acta radiologica. - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 59:12, s. 1438-1445
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Tidskriftsartikel (refereegranskat)abstract
- Background Symptomatic renal artery stenosis (RAS) is mainly treated with pharmacological blood pressure control, sometimes with percutaneous transluminal renal angioplasty (PTRA). It is unclear if PTRA benefits these patients over time. Purpose To determine long-term renal function, morbidity, and mortality in patients with symptomatic RAS treated with PTRA, and whether long-term outcomes are associated with angiographic restenosis. Material and Methods Retrospective single-center, long-term follow-up of 57 patients with atherosclerotic RAS treated with PTRA with stent during 1995-2004 and investigated for restenosis with angiography after one year. Outcomes were retrieved from medical records and from mandatory healthcare registries. Mortality rates were related to expected survival in an age- and gender-matched population, using a life-table database. Surviving patients were assessed with blood pressures, laboratory tests, duplex ultrasonography, and radioisotope renography. Results Median follow-up was 11 years 7 months. Major indications for PTRA were therapy-resistant hypertension and declining renal function. Angiographic restenosis at one year was found in 21 of 57 patients (37%). Thirty-six patients (60%) died during follow-up. Main cause of death was cardiovascular events (54%). Mortality was significantly increased, and morbidity and healthcare utilization were high. Hypertension control during follow-up was stable with persistent need for anti-hypertensive medication, and renal function remained moderately reduced with no long-term difference between patients with vs. without restenosis. Conclusion Long-term prognosis after PTRA for atherosclerotic RAS is dismal, with high mortality and morbidity and reduced renal function, despite maintained hypertension control. Restenosis does not appear to affect late outcome.
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| 47. |
- Zachrisson, Karin, et al.
(författare)
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Results of renal artery revascularization in the post-ASTRAL era with 4 years mean follow-up
- 2020
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Ingår i: Blood Pressure. - : TAYLOR & FRANCIS LTD. - 0803-7051 .- 1651-1999. ; 29:5, s. 285-290
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate contemporary results of percutaneous transluminal renal angioplasty (PTRA).Materials and Methods: A multicentre retrospective study analysing all patients treated with PTRA for primary symptomatic renal artery stenosis (RAS) between 2010 and 2013 at four tertiary centres. Procedures during the preceding four years were counted to evaluate for change in PTRA frequency.Results: The number of PTRA procedures decreased by approximately 50% from 2006 to 2013. Patients treated in the post-ASTRAL period (n = 224) had a significant reduction in mean systolic pressure (168 to 146 mmHg, p < 0.01), diastolic pressure (84 to 76 mmHg, p < 0.01), number of anti-hypertensive drugs (3.54 to 3.05, p < 0.01), and anti-hypertensive treatment index (21.75 to 16.92, p < 0.01) compared to before PTRA. These improvements were maintained at one year and at the last clinical evaluation after a mean follow-up of 4.31 years. Renal function increased transiently without sustained improvement, or deterioration, during later follow-up. Thirteen patients (5.8%) eventually required dialysis, nine of these had eGFR <20 ml/min/1.73 m2 before PTRA. There was no difference in outcomes between subgroups differentiated by different indications for PTRA.Conclusion: The frequency of PTRA has decreased, indicating a higher threshold for invasive treatment of RAS in recent years. The reduction in blood pressures, the reduced need for anti-hypertensive medication, and stabilization of renal function over time suggest a clinical benefit for most patients who are now being treated with PTRA.
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| 48. |
- Zhou, J. M., et al.
(författare)
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Association of Renal Biochemical Parameters with Left Ventricular Diastolic Dysfunction in a Community-Based Elderly Population in China: A Cross-Sectional Study
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Relationship of left ventricular diastolic dysfunction (LVDD) with parameters that could provide more information than hemodynamic renal indexes has not been clarified. We aimed to explore the association of comprehensive renal parameters with LVDD in a community-based elderly population. Methods: 1,166 community residents (aged >= 65 years, 694 females) participating in the Shanghai Heart Health Study with complete data of renal parameters were investigated. Echocardiography was used to evaluate diastolic function with conventional and tissue Doppler imaging techniques. Serum urea, creatinine, urea-to-creatinine ratio, estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were analyzed on their associations with LVDD. Results: The prevalence of LVDD increased in proportion to increasing serum urea, urea-to-creatinine ratio and UACR. These three renal parameters were found negatively correlated to peak early (E) to late (A) diastolic velocities ratio (E/A), and positively to left atrial volume index; UACR also positively correlated with E to peak early (E') diastolic mitral annular velocity ratio (E/E'). Serum urea, urea-to-creatinine ratio and UACR correlated with LVDD in logistic univariate regression analysis, and urea-to-creatinine ratio remained independently correlated to LVDD [ Odds ratio (OR) 2.82, 95% confidence interval (CI) 1.34-5.95] after adjustment. Serum urea (OR 1.18, 95%CI 1.03-1.34), creatinine (OR 6.53, 95%CI 1.70-25.02), eGFR (OR 0.22, 95%CI 0.07-0.65) and UACR (OR 2.15, 95%CI 1.42-3.24) were revealed independent correlates of advanced (moderate and severe) LVDD. Conclusions: Biochemical parameters of renal function were closely linked with LVDD. This finding described new cardiorenal relationship in the elderly population.
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