| 1. |
- Weghuber, D., et al.
(författare)
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A 6-month randomized, double-blind, placebo-controlled trial of weekly exenatide in adolescents with obesity
- 2020
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Ingår i: Pediatric Obesity. - 2047-6302 .- 2047-6310. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pharmacological treatment options for adolescents with obesity are very limited. Glucagon-like-peptide-1 (GLP-1) receptor agonist could be a treatment option for adolescent obesity.OBJECTIVE: To investigate the effect of exenatide extended release on body mass index (BMI)-SDS as primary outcome, and glucose metabolism, cardiometabolic risk factors, liver steatosis, and other BMI metrics as secondary outcomes, and its safety and tolerability in adolescents with obesity.METHODS: Six-month, randomized, double-blinded, parallel, placebo-controlled clinical trial in patients (n = 44, 10-18 years, females n = 22) with BMI-SDS > 2.0 or age-adapted-BMI > 30 kg/m2 according to WHO were included. Patients received lifestyle intervention and were randomized to exenatide extended release 2 mg (n = 22) or placebo (n = 22) subcutaneous injections given once weekly. Oral glucose tolerance tests (OGTT) were conducted at the beginning and end of the intervention.RESULTS: Exenatide reduced (P < .05) BMI-SDS (-0.09; -0.18, 0.00), % BMI 95th percentile (-2.9%; -5.4, -0.3), weight (-3 kg; -5.8, -0.1), waist circumference (-3.2 cm; -5.8, -0.7), subcutaneous adipose tissue (-552 cm3 ; -989, -114), 2-hour-glucose during OGTT (-15.3 mg/dL; -27.5, -3.1), total cholesterol (11.6 mg/dL; -21.7, -1.5), and BMI (-0.83 kg/m2 ; -1.68, 0.01) without significant change in liver fat content (-1.36; -3.12, 0.4; P = .06) in comparison to placebo. Safety and tolerability profiles were comparable to placebo with the exception of mild adverse events being more frequent in exenatide-treated patients.CONCLUSIONS: Treatment of adolescents with severe obesity with extended-release exenatide is generally well tolerated and leads to a modest reduction in BMI metrics and improvement in glucose tolerance and cholesterol. The study indicates that the treatment provides additional beneficial effects beyond BMI reduction for the patient group.
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| 2. |
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| 3. |
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| 4. |
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| 6. |
- Bergström, Mats, et al.
(författare)
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In vivo demonstration of enzyme activity in endocrine pancreatic tumors : decarboxylation of carbon-11-DOPA to carbon-11-dopamine
- 1996
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Ingår i: Journal of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 37:1, s. 32-37
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Tidskriftsartikel (refereegranskat)abstract
- METHODS:We used PET to characterize the uptake and decarboxylation of 11C-L-DOPA in vivo in two patients with endocrine pancreatic tumors: one glucagonoma and one gastrinoma.RESULTS:With L-DOPA labeled with 11C in the beta position, in which the radioactive label follows the molecule through decarboxylation to dopamine, significant uptake was observed in the tumors. With L-DOPA labeled in the carboxyl group, in which the label is rapidly eliminated from the tissue as 11CO2 if decarboxylation takes place, an almost complete lack of uptake is noted.CONCLUSION:This study shows that, using selective position labeling, an in vivo action of enzymatic activity can be observed with PET and that significant decarboxylation occurs in the tested endocrine pancreatic tumors. Also, marked retention of radioactivity occurs after treatment with somatostatin analogs. It is hypothesized that this is a reflection of a reduction of exocytosis which is induced by this treatment.
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| 7. |
- Bjørnerud, Atle, et al.
(författare)
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Assessment of T1 and T2* effects in vivo and ex vivo using iron oxide nanoparticles in steady state : dependence on blood volume and water exchange
- 2002
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 47:3, s. 461-471
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Tidskriftsartikel (refereegranskat)abstract
- Accurate knowledge of the relationship between contrast agent concentration and tissue relaxation is a critical requirement for quantitative assessment of tissue perfusion using contrast-enhanced MRI. In the present study, using a pig model, the relationship between steady-state blood concentration levels of an iron oxide nanoparticle with a hydrated diameter of 12 nm (NC100150 Injection) and changes in the transverse and longitudinal relaxation rates (1/T2* and 1/T1, respectively) in blood, muscle, and renal cortex was investigated at 1.5 T. Ex vivo measurements of 1/T2* and 1/T1 were additionally performed in whole pig blood spiked with different concentrations of the iron oxide nanoparticle. In renal cortex and muscle, 1/T2* increased linearly with contrast agent concentration with slopes of 101 +/-22 s(-1)mM(-1) and 6.5 +/-0.9 s(-1)mM(-1) (mean +/- SD), respectively. In blood, 1/T2* increased as a quadratic function of contrast agent concentration, with different quadratic terms in the ex vivo vs. the in vivo experiments. In vivo, 1/T1 in blood increased linearly with contrast agent concentration, with a slope (T1-relaxivity) of 13.9 +/- 0.9 s(-1)mM(-1). The achievable increase in 1/T1 in renal cortex and muscle was limited by the rate of water exchange between the intra- and extravascular compartments and the 1/T1-curves were well described by a two-compartment water exchange limited relaxation model.
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| 8. |
- Bjørnerud, Atle, et al.
(författare)
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Renal T(*)(2) perfusion using an iron oxide nanoparticle contrast agent : influence of T(1) relaxation on the first-pass response
- 2002
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 47:2, s. 298-304
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative perfusion measurements require accurate knowledge of the correlation between first-pass signal changes and the corresponding tracer concentration in tissue. In the present study, a detailed analysis of first-pass renal cortical changes in T(1) and T(*)(2) following bolus injection of the iron oxide nanoparticle NC100150 Injection was investigated in a pig model using a double-echo gradient-echo sequence. The estimated change in 1/T(*)(2) during first pass calculated from single-echo sequences was compared to the true double-echo-derived 1/T(*)(2) curves. Using a single-echo (TE = 6 ms) spoiled gradient-echo sequence, the first-pass 1/T(*)(2) response following a bolus injection of 1 mg Fe/kg of NC100150 Injection was significantly underestimated due to counteracting T(1) effects. Signal response simulations showed that the relative error in the first-pass response decreased with increasing TE and contrast agent dose. However, both the maximum TE and the maximum dose are limited by excessive cortical signal loss, and the maximum TE is further limited by high temporal resolution requirements. The problem of T(1) contamination can effectively be overcome by using a double-echo gradient-echo sequence. This yields a first-pass response that truly reflects the tissue tracer concentration, which is a critical requirement for quantitative renal perfusion assessment.
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| 9. |
- Briley-Saebo, Karen C., et al.
(författare)
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Clearance of iron oxide particles in rat liver : effect of hydrated particle size and coating material on liver metabolism
- 2006
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Ingår i: Investigative Radiology. - : Ovid Technologies (Wolters Kluwer Health). - 0020-9996 .- 1536-0210. ; 41:7, s. 560-571
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We sought to evaluate the effect of the particle size and coating material of various iron oxide preparations on the rate of rat liver clearance. MATERIALS AND METHODS: The following iron oxide formulations were used in this study: dextran-coated ferumoxide (size = 97 nm) and ferumoxtran-10 (size = 21 nm), carboxydextran-coated SHU555A (size = 69 nm) and fractionated SHU555A (size = 12 nm), and oxidized-starch coated materials either unformulated NC100150 (size = 15 nm) or formulated NC100150 injection (size = 12 nm). All formulations were administered to 165 rats at 2 dose levels. Quantitative liver R2* values were obtained during a 63-day time period. The concentration of iron oxide particles in the liver was determined by relaxometry, and these values were used to calculate the particle half-lives in the liver. RESULTS: After the administration of a high dose of iron oxide, the half-life of iron oxide particles in rat liver was 8 days for dextran-coated materials, 10 days for carboxydextran materials, 14 days for unformulated oxidized-starch, and 29 days for formulated oxidized-starch. CONCLUSIONS: The results of the study indicate that materials with similar coating but different sizes exhibited similar rates of liver clearance. It was, therefore, concluded that the coating material significantly influences the rate of iron oxide clearance in rat liver.
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| 10. |
- Carlson, K, et al.
(författare)
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MR imaging of multiple myeloma in tumour mass measurement at diagnosis and during treatment
- 1995
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Ingår i: Acta Radiologica. - 0284-1851 .- 1600-0455. ; 36:1, s. 9-14
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Tidskriftsartikel (refereegranskat)abstract
- The bone marrow of the spine, pelvis and proximal femora was examined with MR imaging at diagnosis in 30 cases of multiple myeloma (MM), and during treatment on 69 occasions. The MR pattern was normal, focal or diffuse and correlated to stage. A tumour mass index (TMI) was calculated by estimating the total myeloma mass visualised at MR imaging. The TMI correlated significantly with stage, lytic bone lesions, serum calcium, serum beta-2-microglobulin and survival. No abnormalities were seen at MR investigation in 4 of 6 patients classified as stage II because of osteoporosis only. Therapy efficacy evaluation with MR imaging corresponded to clinical evaluation on 54 of the 69 occasions. MR examination of bone marrow in MM patients can be used for tumour mass assessment, both at diagnosis and during follow-up. Valuable information can be obtained when the tumour mass is difficult to estimate using clinical criteria, e.g. in non-secretory MM or when osteoporosis is the only variable indicating an increase in the tumour mass.
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| 11. |
- Elmsjö, Albert, et al.
(författare)
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NMR-based metabolic profiling in healthy individuals overfed different types of fat : links to changes in liver fat accumulation and lean tissue mass.
- 2015
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Ingår i: Nutrition & Diabetes. - : Springer Science and Business Media LLC. - 2044-4052. ; 5:19, s. e182-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Overeating different dietary fatty acids influence the amount of liver fat stored during weight gain, however, the mechanisms responsible are unclear. We aimed to identify non-lipid metabolites that may differentiate between saturated (SFA) and polyunsaturated fatty acid (PUFA) overfeeding using a non-targeted metabolomic approach. We also investigated the possible relationships between plasma metabolites and body fat accumulation.METHODS: In a randomized study (LIPOGAIN study), n=39 healthy individuals were overfed with muffins containing SFA or PUFA. Plasma samples were precipitated with cold acetonitrile and analyzed by nuclear magnetic resonance (NMR) spectroscopy. Pattern recognition techniques were used to overview the data, identify variables contributing to group classification and to correlate metabolites with fat accumulation.RESULTS: We previously reported that SFA causes a greater accumulation of liver fat, visceral fat and total body fat, whereas lean tissue levels increases less compared with PUFA, despite comparable weight gain. In this study, lactate and acetate were identified as important contributors to group classification between SFA and PUFA (P<0.05). Furthermore, the fat depots (total body fat, visceral adipose tissue and liver fat) and lean tissue correlated (P(corr)>0.5) all with two or more metabolites (for example, branched amino acids, alanine, acetate and lactate). The metabolite composition differed in a manner that may indicate higher insulin sensitivity after a diet with PUFA compared with SFA, but this needs to be confirmed in future studies.CONCLUSION: A non-lipid metabolic profiling approach only identified a few metabolites that differentiated between SFA and PUFA overfeeding. Whether these metabolite changes are involved in depot-specific fat storage and increased lean tissue mass during overeating needs further investigation.
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| 12. |
- Eriksson, Olof, et al.
(författare)
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The Positron Emission Tomography ligand [11C]5-Hydroxy-Tryptophan can be used as a surrogate marker for the human endocrine pancreas
- 2014
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 63:10, s. 3428-3437
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Tidskriftsartikel (refereegranskat)abstract
- In humans a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of beta cells, with healthy volunteers (HV).C-peptide negative (i.e. insulin-deficient) T1D subjects (n=10) and HV (n=9) underwent dynamic Positron Emission Tomography with the radiolabeled serotonin precursor [(11)C]5-Hydroxy-Tryptophan ([(11)C]5-HTP).A significant accumulation of [(11)C]5-HTP was obtained in the pancreas of the HV, with large inter-individual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [(11)C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where beta-cells normally are the major constituent of the islets.[(11)C]5-HTP retention in the pancreas was reduced in T1D compared to non-diabetic subjects. Accumulation of [(11)C]5-HTP in the pancreas of both HV and subjects with T1D were in agreement with previously reported morphological observations on the beta cell volume implying that [(11)C]5-HTP retention is a useful non-invasive surrogate marker for the human endocrine pancreas.
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| 15. |
- Langner, Taro, et al.
(författare)
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Uncertainty-Aware Body Composition Analysis with Deep Regression Ensembles on UK Biobank MRI
- 2021
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Ingår i: Computerized Medical Imaging and Graphics. - : Elsevier BV. - 0895-6111 .- 1879-0771. ; 93
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Tidskriftsartikel (refereegranskat)abstract
- Along with rich health-related metadata, an ongoing imaging study has acquired MRI of over 40,000 male and female UK Biobank participants aged 44-82 since 2014. Phenotypes derived from these images, such as measurements of body composition, can reveal new links between genetics, cardiovascular disease, and metabolic conditions. In this retrospective study, six measurements of body composition were automatically estimated by ResNet50 neural networks for image-based regression from neck-to-knee body MRI. Despite the potential for high speed and accuracy, these networks produce no output segmentations that could indicate the reliability of individual measurements. The presented experiments therefore examine mean-variance regression and ensembling for predictive uncertainty estimation, which can quantify individual measurement errors and thereby help to identify potential outliers, anomalies, and other failure cases automatically. In 10-fold cross-validation on data of about 8,500 subjects, mean-variance regression and ensembling showed complementary benefits, reducing the mean absolute error across all predictions by 12%. Both improved the calibration of uncertainties and their ability to identify high prediction errors. With intra-class correlation coefficients (ICC) above 0.97, all targets except the liver fat content yielded relative measurement errors below 5%. Testing on another 1,000 subjects showed consistent performance, and the method was finally deployed for inference to 30,000 subjects with missing reference values. The results indicate that deep regression ensembles could ultimately provide automated, uncertainty-aware measurements of body composition for more than 120,000 UK Biobank neck-to-knee body MRI that are to be acquired within the coming years.
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| 16. |
- Letocha, H, et al.
(författare)
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Positron emission tomography with L-methyl-11C-methionine in the monitoring of therapy response in muscle-invasive transitional cell carcinoma of the urinary bladder
- 1994
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Ingår i: British Journal of Urology. - 0007-1331 .- 1365-2176. ; 74:6, s. 767-774
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether positron emission tomography (PET) with L-methyl-11C-methionine as a tracer could be used for diagnostic purposes and for evaluation of therapy in patients with varying stages of urinary bladder cancer treated with chemotherapy. PATIENTS AND METHODS: PET was employed in 44 separate examinations involving 29 patients (24 men and five women with a median age of 68 years [mean 66, range 47-78]) with localized or metastatic transitional cell carcinoma of the urinary bladder. In four patients PET examinations were performed prior to the commencement of chemotherapy, and after one course and after three courses. RESULTS: The diagnostic accuracy of PET was poor. The technique did not monitor the therapeutic effect of neoadjuvant chemotherapy, producing results that correlated with therapy outcome. PET identified those patients who responded less successfully to therapy. CONCLUSION: PET with L-methyl-11C-methionine demonstrates alterations in tumour metabolism long before visible changes appear on computed tomography or magnetic resonance imaging. Further work is required to develop more specific tracers.
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| 17. |
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| 18. |
- Nelson, A E, et al.
(författare)
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Diagnosis of a patient with oncogenic osteomalacia using a phosphate uptake bioassay of serum and magnetic resonance imaging
- 2001
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 145:4, s. 469-476
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Tidskriftsartikel (refereegranskat)abstract
- A previously healthy man with no family history of fractures presented with muscle pain, back pain and height loss. Investigations revealed hypophosphataemia, phosphaturia, undetectable serum 1,25-dihydroxyvitamin D and severe osteomalacia on bone biopsy, suggestive of a diagnosis of oncogenic osteomalacia. Thorough physical examination did not locate a tumour. Support for the diagnosis was obtained by detection of phosphate uptake inhibitory activity in a blinded sample of the patient's serum using a renal cell bioassay. On the basis of detection of this bioactivity, a total body magnetic resonance (MR) examination was performed. A small tumour was located in the right leg. Removal of the tumour resulted in the rapid reversal of symptoms and the abnormal biochemistry typical of oncogenic osteomalacia. Inhibitory activity was also demonstrated using the bioassay in serum from two other patients with confirmed or presumptive oncogenic osteomalacia, but not in serum from two patients with hypophosphataemia of other origin. This is the first case to be reported in which the diagnosis of oncogenic osteomalacia was assisted by demonstration of inhibitory activity of the patient's serum in a renal cell phosphate bioassay that provided an impetus for total body MR imaging.
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| 19. |
- Stenlid, Rasmus, et al.
(författare)
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High DPP-4 concentrations in adolescents are associated with low intact GLP-1
- 2018
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 103:8, s. 2958-2966
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Tidskriftsartikel (refereegranskat)abstract
- Context: Dipeptidyl Peptidase-4 (DPP-4) metabolizes glucagon-like peptide-1 (GLP-1) and increased DPP4 levels are associated with obesity and visceral adiposity in adults.Objective: Investigating DPP-4 levels in adolescents and association with, firstly, circulating intact GLP-1 levels and glucose tolerance, secondly, BMI, and, thirdly visceral, subcutaneous and liver fat compartments.Design: Cross-sectional study, July 2012 to April 2015.Setting: Pediatric obesity clinic, Uppsala University Hospital.Patients and participants: Children and adolescents with obesity (n=59) and lean controls (n=21), age 8-18.Main outcome measures: BMI SDS, fasting plasma concentrations of DPP-4, total and intact GLP-1, fasting and OGTT concentrations of glucose and visceral (VAT) and subcutaneous (SAT) adipose tissue volumes and liver fat fraction.Results: Plasma DPP-4 decreased with age both in obese (41 ng/ml per year) and lean subjects (48 ng/ml per year). Plasma DPP-4 was higher in males both in the obesity and lean group. When adjusting for age and sex, plasma DPP-4 was negatively associated with intact GLP-1 at fasting, B=-12.3, 95% CI [-22.9, -1.8] and during OGTT, B=-12.1, 95% CI [-22.5, -1.7]. No associations were found between DPP-4 and plasma glucose measured at fasting or after a 2-hour OGTT. Plasma DPP-4 was 19% higher in the obese subjects. Among adipose tissue compartments the strongest association was with VAT, B=0.05, 95% CI [-0.02, 0.12].Conclusions: In adolescents, high plasma DPP-4 concentrations are associated with low proportion of intact GLP-1, high BMI, young age and male sex. The observed associations are compatible with an increased metabolism of GLP-1 in childhood obesity.
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| 20. |
- Tammela, T L, et al.
(författare)
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An Intraprostatic Modified Release Formulation of Antiandrogen 2-Hydroxyflutamide for Localized Prostate Cancer
- 2017
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 198:6, s. 1333-1339
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate tolerability, safety and antitumor effects of a novel intra-prostatic depot formulation of antiandrogen 2-hydroxyflutamide (2-HOF in NanoZolid(®)) in men with localized prostate cancer (PCa).MATERIALS AND METHODS: Two clinical trials, LPC-002 and LPC-003, were conducted on a total of 47 men. The formulation was injected transrectally into the prostate with ultrasound guidance. In LPC-002 the effects on prostate specific antigen (PSA) and prostate volume (PV) were measured over 6 months on 24 patients. In LPC-003, antitumor effects were evaluated with histopathology, magnetic resonance imaging (MRI) including spectroscopy (MRS) during 6 or 8 weeks on 23 patients. In both studies, testosterone and 2-HOF in plasma were measured, as well as quality-of-life parameters.RESULTS: In LPC-002 (mean dose 690 mg) a reduction in PSA and PV was observed. The nadir values for PSA and PV were on average 24.9 % and 14.0 % below baseline, respectively. When increasing the dose in LPC-003 (920 mg and 1740 mg), the average PSA dropped 16 % and 23 %, respectively, after 6 and 8 weeks. MRI/MRS showed morphological changes and a global drop in metabolite concentrations following treatment indicating an antitumor response. The injections did not result in hormone related side effects. In total, three serious adverse events were reported, all resolved by oral antibiotic treatment.CONCLUSIONS: The intraprostatic injections of 2-HOF depot formulations indicated anti-tumor effects and proved safe and tolerable. However, for better anti-cancer effects higher doses and better dose distribution are suggested.
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| 21. |
- Wikström, Johan, et al.
(författare)
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Abdominal vessel enhancement with an ultrasmall, superparamagnetic iron oxide blood pool agent : evaluation of dose and echo time dependence at different field strengths
- 1999
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Ingår i: Academic Radiology. - 1076-6332 .- 1878-4046. ; 6:5, s. 292-298
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE AND OBJECTIVES: The purpose of the study was to determine the dose and echo time dependence of abdominal vessel enhancement at magnetic resonance (MR) imaging after injection of a blood pool contrast agent at two field strengths. MATERIALS AND METHODS: Sixteen healthy volunteers received NC100150 Injection at three dose levels (1.0 mg, 2.5 mg, and 4.0 mg of iron per kilogram of body weight). Images of the aorta and inferior vena cava (IVC) were obtained at 0.5 or 1.5 T. Four sequences with varying echo times were used with each subject. Signal intensities were recorded from the aorta, IVC, vessel vicinity, air, and a marker outside the patient. Contrast-to-noise ratios (CNRs) were calculated for the vessels. Aortic delineation was subjectively evaluated. RESULTS: Images with the highest mean vessel signal intensities, subjectively assessed as satisfactory for aortic delineation, were obtained with 2.5-4.0 mg of iron per kilogram of body weight at both field strengths. The highest CNR was found with 4.0 mg of iron per kilogram of body weight at 1.5 T. An increase in echo time caused larger signal intensity loss at larger dose levels. The signal intensity from the IVC was higher than that of the aorta at all dose levels, echo times, and field strengths. CONCLUSION: NC100150 Injection is an efficient T1-reducing agent at both 0.5 and 1.5 T. A positive dose response for CNR of the aorta and IVC was seen at 1.5 T.
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