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  • Kullberg, J, et al. (författare)
  • Whole-body adipose tissue analysis: comparison of MRI, CT and dual energy X-ray absorptiometry.
  • 2009
  • Ingår i: The British journal of radiology. - 1748-880X .- 0007-1285. ; 82:974, s. 123-30
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to validate a recently proposed MRI-based T(1)-mapping method for analysis of whole-body adipose tissue (AT) using an established CT protocol as reference and to include results from dual energy X-ray absorptiometry (DEXA). 10 subjects, drawn from the Swedish Obese Subjects Sibling-pairs study, were examined using CT, MRI and DEXA. The CT analysis was based on 28 imaged slices. T(1) maps were calculated using contiguous MRI data from two different gradient echo sequences acquired using different flip angles. CT and MRI comparison was performed slice-wise and for the whole-body region. Fat weights were compared between all three modalities. Strong correlations (r > or = 0.977, p<0.0001) were found between MRI and CT whole-body and AT volumes. MRI visceral AT volume was underestimated by 0.79 +/- 0.75 l (p = 0.005), but total AT was not significantly different from that estimated by CT (MRI - CT = -0.61+/-1.17 l; p = 0.114). DEXA underestimated fat weights by 5.23 +/- 1.71 kg (p = 0.005) compared with CT. MRI underestimated whole-body volume by 2.03 +/- 1.61 l (p = 0.005) compared with CT. Weights estimated either by CT or by DEXA were not significantly different from weights measured using scales. In conclusion, strong correlations were found between whole-body AT results from CT, MRI-based T(1) mapping and DEXA. If the differences between the results from T(1)-mapping and CT-based analysis are accepted, the T(1)-mapping method allows fully automated post-processing of whole-body MRI data, allowing longitudinal whole-body studies that are also applicable for children and adolescents.
  • Edholm, David, et al. (författare)
  • Preoperative 4-week low-calorie diet reduces liver volume and intrahepatic fat, and facilitates laparoscopic gastric bypass in morbidly obese
  • 2011
  • Ingår i: Obesity Surgery. - 0960-8923 .- 1708-0428. ; 21:3, s. 345-350
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The aim of this study was to explore changes in liver volume and intrahepatic fat in morbidly obese patients during 4 weeks of low-calorie diet (LCD) before surgery and to investigate if these changes would facilitate the following laparoscopic gastric bypass.METHODS: Fifteen female patients (121.3 kg, BMI 42.9) were treated preoperatively in an open study with LCD (800-1,100 kcal/day) during 4 weeks. Liver volume and fat content were assessed by magnetic resonance imaging and spectroscopy before and after the LCD treatment.RESULTS: Liver appearance and the complexity of the surgery were scored at the operation. Eighteen control patients (114.4 kg, BMI 40.8), without LCD were scored similarly. Average weight loss in the LCD group was 7.5 kg, giving a mean weight of 113.9 kg at surgery. Liver volume decreased by 12% (p < 0.001) and intrahepatic fat by 40% (p < 0.001). According to the preoperative scoring, the size of the left liver lobe, sharpness of the liver edge, and exposure of the hiatal region were improved in the LCD group compared to the controls (all p < 0.05).CONCLUSIONS: The overall complexity of the surgery was perceived lower in the LCD group (p < 0.05), due to improved exposure and reduced psychological stress (both p < 0.05). Four weeks of preoperative LCD resulted in a significant decrease in liver volume and intrahepatic fat content, and facilitated the subsequent laparoscopic gastric bypass as scored by the surgeon
  • Eriksson, Jan W, 1959, et al. (författare)
  • Hydrochlorothiazide, but not Candesartan, aggravates insulin resistance and causes visceral and hepatic fat accumulation: the mechanisms for the diabetes preventing effect of Candesartan (MEDICA) study
  • 2008
  • Ingår i: Hypertension. - : American Heart Association. - 0194-911X .- 1524-4563. ; 52:6, s. 1030-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Treatment with angiotensin II receptor blockers is associated with lower risk for the development of type 2 diabetes mellitus compared with thiazide diuretics. The Mechanisms for the Diabetes Preventing Effect of Candesartan Study addressed insulin action and secretion and body fat distribution after treatment with candesartan, hydrochlorothiazide, and placebo. Twenty-six nondiabetic, abdominally obese, hypertensive patients were included in a multicenter 3-way crossover trial, and 22 completers (by predefined criteria; 10 men and 12 women) were included in the analyses. They underwent 12-week treatment periods with candesartan (C; 16 to 32 mg), hydrochlorothiazide (H; 25 to 50 mg), and placebo (P), respectively, and the treatment order was randomly assigned and double blinded. Intravenous glucose tolerance tests and euglycemic hyperinsulinemic (56 mU/m2 per minute) clamps were performed. Intrahepatic and intramyocellular and extramyocellular lipid content and subcutaneous and visceral abdominal adipose tissue were measured using proton magnetic resonance spectroscopy and MRI. Insulin sensitivity (M-value) was reduced following H versus C and P (6.07±2.05, 6.63±2.04, and 6.90±2.10 mg/kg of body weight per minute, mean±SD; P≤0.01). Liver fat content was higher (P<0.05) following H than both P and C. The subcutaneous to visceral abdominal adipose tissue ratio was reduced following H versus C and P (P<0.01). Glycosylated hemoglobin, alanine aminotransferase, aspartate aminotransferase, and high-sensitivity C-reactive protein levels were higher (P<0.05) after H, but not C, versus P. There were no changes in body fat, intramyocellular lipid, extramyocellular lipid, or first-phase insulin secretion. Blood pressure was reduced similarly by C and H versus P. In conclusion, visceral fat redistribution, liver fat accumulation, low-grade inflammation, and aggravated insulin resistance were demonstrated after hydrochlorothiazide but not candesartan treatment. These findings can partly explain the diabetogenic potential of thiazides.
  • Eriksson, Rolf, 1979- (författare)
  • The Utility of Manganese for Magnetic Resonance Imaging of Transient Myocardial Ischemia
  • 2005
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • In order to improve the diagnosis of coronary artery disease, better methods for detection of myocardial perfusion defects would be useful. One of the methods used for myocardial perfusion evaluation today is magnetic resonance imaging. This method could be improved if a contrast agent that induced long-lasting contrast enhancement in the myocardium could be developed. The paramagnetic manganese(II) ion has promising properties for meeting this need, since it enters cardiomyocytes through voltage-gated calcium channels and remains inside the cells for a long time after an intravenous injection. If these properties can be utilized, manganese-enhanced MRI has potential for detecting transient periods of ischemia in a manner similar to the conventional SPECT stress test.To investigate the contrast-enhancing properties of the manganese(II) ion, a series of experiments was performed in pigs, using a manganese salt (MnCl2) and two manganese-based chelates (MnDPDP and MnHPTA) and measuring the longitudinal relaxation rates before and after contrast agent administration. This was done in normal pig myocardium at rest and during dobutamine-induced stress with several different doses of contrast agent, and in a model for coronary artery stenosis using MnCl2 administered during dobutamine stress to determine whether transient ischemia could be detected with this contrast agent.The results of these experiments showed that of the three contrast agents, MnCl2 induces the greatest increase in ΔR1, followed by MnHPTA. Using MnCl2 it was possible to produce images on which transient myocardial ischemia was visible, but only during the first 30 minutes after contrast agent injection.The stenosis model is still far from the clinical situation and several complications, including the potential toxicity of the manganese(II) ion, remain to be overcome. However, the results from this model are promising for the future development of manganese- enhanced magnetic resonance imaging of transient myocardial ischemia.
  • Glimelius, Bengt, et al. (författare)
  • U-CAN : a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
  • 2018
  • Ingår i: Acta Oncologica. - : Taylor & Francis Group. - 0284-186X .- 1651-226X. ; 57:2, s. 187-194
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.
  • Hagström, Emil, et al. (författare)
  • Plasma-parathyroid hormone is associated with subclinical and clinical atherosclerotic disease in 2 community-based cohorts
  • 2014
  • Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 34:7, s. 1567-1579
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Cardiovascular risk factors have different impact on different arterial territories. Diseases with elevated circulating parathyroid hormone (PTH) such as primary hyperparathyroidism and chronic renal failure have been shown to be associated with an increased risk of cardiovascular disease, predominantly heart or cerebrovascular diseases. However, data on the associations between circulating PTH and peripheral atherosclerosis are limited.APPROACH AND RESULTS: Two prospective, community-based studies were used. In 306 men and women, who were 70 years old, from the Prospective investigation of the vasculature in Uppsala seniors (PIVUS) study, cross-sectional relations between PTH and atherosclerotic burden assessed by whole-body magnetic resonance angiography were investigated. In 998 men, who were 71 years old, from the Uppsala longitudinal study of adult men (ULSAM) study, the association between PTH concentration and risk of subsequent nonfatal atherosclerotic disease (excluding coronary or cerebrovascular disease) was investigated. Adjusting for established vascular risk factors, PTH was associated with burden of atherosclerosis (increase in total atherosclerotic score per SD PTH increase: 0.04, 0.003-0.08; P=0.03) in the PIVUS study. During follow-up in the ULSAM study (median 16.7 years), 89 men were diagnosed with nonfatal atherosclerotic disease. In Cox-regression analyses adjusting for established vascular risk factors and mineral metabolism, higher PTH was associated with an increased risk of nonfatal atherosclerotic disease (hazard ratio for 1 SD increase of PTH: 1.55, 1.33-1.88; P<0.0001). Results were similar when including fatal atherosclerotic disease in the outcome.CONCLUSIONS: In 2 independent community-based cohorts, PTH was associated to the degree of atherosclerosis and risk of clinically overt atherosclerotic disease, respectively. Our data confirm and extend previous studies supporting a role for PTH in the development of atherosclerotic disease.
  • Hagström, Emil, et al. (författare)
  • Plasma parathyroid hormone is associated with vascular dementia and cerebral hyperintensities in two community-based cohorts
  • 2014
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - 0021-972X .- 1945-7197. ; 99:11, s. 4181-4189
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: In diseases with increased PTH such as hyperparathyroidism and chronic renal failure, dementia is common. Little is known of PTH and dementia in the community.Objective: We sought to investigate relations between PTH, clinical dementia and cerebral micro-vascular disease. Setting and Design: The Uppsala Longitudinal Study Of Adult Men (ULSAM) was prospective, baseline, 1991-1995; followup, 15.8 years. The Prospective Investigation Of The Vasculature In Uppsala Seniors (PIVUS) was cross-sectional, baseline, 2001. Both settings were community based.Participants and Main Outcome Measure: In the ULSAM study of 998 men (age 71) the association between PTH and dementia was investigated. In the PIVUS study of 406 men and women (age 70) the relation between PTH and magnetic resonance imaging signs of cerebral small vascular disease was investigated.Results: During followup, 56 individuals were diagnosed with vascular, 91 with Alzheimer's, and 59 with other dementias. In Cox-regression analyses, higher PTH was associated with vascular dementia (hazard ratio per 1 SD increase of PTH, 1.41; P < .01), but not with other dementias. The top tertile of PTH accounted for 18.5% of the population-attributable risk for vascular dementia, exceeding all other risk factors. In linear regression analysis in PIVUS, PTH was associated with increasing white matter hyperintensities (WMHI), reflecting increasing burden of cerebral small vessel disease (1 SD PTH increase, 0.31 higher category of WMHI; P = .016). All models were adjusted for vascular risk factors and mineral metabolism.Conclusions: In two community-based samples, PTH predicted clinically diagnosed and neuroimaging indices of vascular dementia and cerebral small vessel disease. Our data suggest a role for PTH in the development of vascular dementia.
  • Hammar, Per, et al. (författare)
  • Unrecognized myocardial infarctions assessed by cardiovascular magnetic resonance are associated with the severity of the stenosis in the supplying coronary artery
  • 2015
  • Ingår i: Journal of Cardiovascular Magnetic Resonance. - : BioMed Central. - 1097-6647 .- 1532-429X. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A previous study has shown an increased prevalence of late gadolinium enhancement cardiovascular magnetic resonance (LGE CMR) detected unrecognized myocardial infarction (UMI) with increasing extent and severity of coronary artery disease. However, the coronary artery disease was evaluated on a patient level assuming normal coronary anatomy. Therefore, the aims of the present study were to investigate the prevalence of UMI identified by LGE CMR imaging in patients with stable angina pectoris and no known previous myocardial infarction; and to investigate whether presence of UMI is associated with stenotic lesions in the coronary artery supplying the segment of the myocardium in which the UMI is located, using coronary angiography to determine the individual coronary anatomy in each patient.Methods: In this prospective multicenter study, we included patients with stable angina pectoris and without prior myocardial infarction, scheduled for coronary angiography. A LGE CMR examination was performed prior to the coronary angiography. The study cohort consisted of 235 patients (80 women, 155 men) with a mean age of 64.8 years.Results: UMIs were found in 25 % of patients. There was a strong association between stenotic lesions (>= 70 % stenosis) in a coronary artery and the presence of an UMI in the myocardial segments supplied by the stenotic artery; it was significantly more likely to have an UMI downstream a stenosis >= 70 % as compared to <70 % (OR 5.1, CI 3.1-8.3, p < 0.0001). 56 % of the UMIs were located in the inferior and infero-lateral myocardial segments, despite predominance for stenotic lesions in the left anterior descending artery.Conclusion: UMI is common in patients with stable angina and the results indicate that the majority of the UMIs are of ischemic origin due to severe coronary atherosclerosis. In contrast to what is seen in recognized myocardial infarctions, UMIs are predominately located in the inferior and infero-lateral myocardial segments.
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