| 1. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Management of disseminated midgut carcinoid tumours.
- 1991
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Ingår i: Digestion. - 0012-2823. ; 49:2, s. 78-96
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Tidskriftsartikel (refereegranskat)abstract
- Forty-one patients with disseminated midgut carcinoid tumours were treated over a 6-year period according to a strict programme including primary surgical treatment. In 10 patients, a total remission of the disease was obtained. Patients with bilobar hepatic disease had ischaemic treatment of their liver metastases by hepatic arterial embolisation after primary surgical and medical treatment (low dose octreotide). Thus, by combining surgical, radiological and medical treatment modalities, we wanted to offer these patients optimal palliation. This treatment programme resulted in good symptomatic relief in all patients accompanied by a marked reduction in 5-hydroxyindoleacetic acid (5-HIAA) levels. At recurrence of symptoms in combination with rising 5-HIAA levels, embolisation was repeated. Ten of the treated patients have deceased during the observation period, but only 5 from their carcinoid disease.
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| 2. |
- Ahmed, Mona, et al.
(författare)
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Cellular Uptake of Plain and SPION-Modified Microbubbles for Potential Use in Molecular Imaging
- 2017
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Ingår i: Cellular and Molecular Bioengineering. - : SPRINGER. - 1865-5025 .- 1865-5033. ; 10:6, s. 537-548
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Tidskriftsartikel (refereegranskat)abstract
- Both diagnostic ultrasound (US) and magnetic resonance imaging (MRI) accuracy can be improved by using contrast enhancement. For US gas-filled microbubbles (MBs) or silica nanoparticles (SiNPs), and for MRI superparamagnetic or paramagnetic agents, contribute to this. However, interactions of MBs with the vascular wall and cells are not fully known for all contrast media. We studied the in vitro interactions between three types of non-targeted air-filled MBs with a polyvinyl-alcohol shell and murine macrophages or endothelial cells. The three MB types were plain MBs and two types that were labelled (internally and externally) with superparamagnetic iron oxide nanoparticles (SPIONs) for US/MRI bimodality. Cells were incubated with MBs and imaged by microscopy to evaluate uptake and adhesion. Interactions were quantified and the MB internalization was confirmed by fluorescence quenching of non-internalized MBs. Macrophages internalized each MB type within different time frames: plain MBs 6 h, externally labelled MBs 25 min and internally labelled MBs 2 h. An average of 0.14 externally labelled MBs per cell were internalized after 30 min and 1.34 after 2 h; which was 113% more MBs than the number of internalized internally labelled MBs. The macrophages engulfed these three differently modified new MBs at various rate, whereas endothelial cells did not engulf MBs. Polyvinyl-alcohol MBs are not taken up by endothelial cells. The MB uptake by macrophages is promoted by SPION labelling, in particular external such, which may be important for macrophage targeting.
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| 3. |
- Ahmed, M., et al.
(författare)
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Human serum albumin-based probes for molecular targeting of macrophage scavenger receptors
- 2019
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Ingår i: International Journal of Nanomedicine. - 1176-9114 .- 1178-2013. ; 14, s. 3723-3741
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inflammation and accumulation of macrophages are key features of unstable atherosclerotic plaques. The ability of macrophages to take up molecular probes can be exploited in new clinical imaging methods for the detection of unstable atherosclerotic lesions. We investigated whether modifications of human serum albumin (HSA) could be used to target macrophages efficiently in vitro. Materials and methods: Maleylated and aconitylated HSA were compared with unmodified HSA. Fluorescent or radiolabeled (89 Zr) modified HSA was used in in vitro experiments to study cellular uptake by differentiated THP-1 cells and primary human macrophages. The time course of uptake was evaluated by flow cytometry, confocal microscopy, real-time microscopy and radioactivity measurements. The involvement of scavenger receptors (SR-A1, SR-B2, LOX-1) was assessed by knockdown experiments using RNA interference, by blocking experiments and by assays of competition by modified low-density lipoprotein. Results: Modified HSA was readily taken up by different macrophages. Uptake was mediated nonexclusively via the scavenger receptor SR-A1 (encoded by the MSR1 gene). Knockdown of CD36 and ORL1 had no influence on the uptake. Modified HSA was preferentially taken up by human macrophages compared with other vascular cell types such as endothelial cells and smooth muscle cells. Conclusions: Modified89Zr-labeled HSA probes were recognized by different subsets of polarized macrophages, and maleylated HSA may be a promising radiotracer for radio-nuclide imaging of macrophage-rich inflammatory vascular diseases. © 2019 Ahmed et al.
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| 4. |
- Ahmed, M., et al.
(författare)
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Molecular Imaging of a New Multimodal Microbubble for Adhesion Molecule Targeting
- 2019
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Ingår i: Cellular and Molecular Bioengineering. - : Springer Science and Business Media LLC. - 1865-5025 .- 1865-5033. ; 12:1, s. 15-32
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionInflammation is an important risk-associated component of many diseases and can be diagnosed by molecular imaging of specific molecules. The aim of this study was to evaluate the possibility of targeting adhesion molecules on inflammation-activated endothelial cells and macrophages using an innovative multimodal polyvinyl alcohol-based microbubble (MB) contrast agent developed for diagnostic use in ultrasound, magnetic resonance, and nuclear imaging.MethodsWe assessed the binding efficiency of antibody-conjugated multimodal contrast to inflamed murine or human endothelial cells (ECs), and to peritoneal macrophages isolated from rats with peritonitis, utilizing the fluorescence characteristics of the MBs. Single-photon emission tomography (SPECT) was used to illustrate Tc-99m-labeled MB targeting and distribution in an experimental in vivo model of inflammation.ResultsFlow cytometry and confocal microscopy showed that binding of antibody-targeted MBs to the adhesion molecules ICAM-1, VCAM-1, or E-selectin, expressed on cytokine-stimulated ECs, was up to sixfold higher for human and 12-fold higher for mouse ECs, compared with that of non-targeted MBs. Under flow conditions, both VCAM-1- and E-selectin-targeted MBs adhered more firmly to stimulated human ECs than to untreated cells, while VCAM-1-targeted MBs adhered best to stimulated murine ECs. SPECT imaging showed an approximate doubling of signal intensity from the abdomen of rats with peritonitis, compared with healthy controls, after injection of anti-ICAM-1-MBs.ConclusionsThis novel multilayer contrast agent can specifically target adhesion molecules expressed as a result of inflammatory stimuli in vitro, and has potential for use in disease-specific multimodal diagnostics in vivo using antibodies against targets of interest.
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| 5. |
- Ahmed, M., et al.
(författare)
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Molecular Imaging of Inflammation in a Mouse Model of Atherosclerosis Using a Zirconium-89-Labeled Probe
- 2020
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Ingår i: International Journal of Nanomedicine. - 1178-2013. ; 15, s. 6137-6152
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Tidskriftsartikel (refereegranskat)abstract
- Background: Beyond clinical atherosclerosis imaging of vessel stenosis and plaque morphology, early detection of inflamed atherosclerotic lesions by molecular imaging could improve risk assessment and clinical management in high-risk patients. To identify inflamed atherosclerotic lesions by molecular imaging in vivo, we studied the specificity of our radiotracer based on maleylated (Mal) human serum albumin (HSA), which targets key features of unstable atherosclerotic lesions. Materials and Methods: Mal-HSA was radiolabeled with a positron-emitting metal ion, zirconium-89 (Zr-89(4+)). The targeting potential of this probe was compared with unspecific Zr-89-HSA and F-18-FDG in an experimental model of atherosclerosis (Apoe(-/-) mice, n=22), and compared with wild-type (WT) mice (C57BL/6J, n=21) as controls. Results: PET/MRI, gamma counter measurements, and autoradiography showed the accumulation of Zr-89-Mal-HSA in the atherosclerotic lesions of Apoe(-/-) mice. The maximum standardized uptake values (SUVmax) for Zr-89-Mal-HSA at 16 and 20 weeks were 26% and 20% higher (P<0.05) in Apoe(-/-) mice than in control WT mice, whereas no difference in SUVmax was observed for F-18-FDG in the same animals. Zr-89-Mal-HSA uptake in the aorta, as evaluated by a gamma counter 48 h postinjection, was 32% higher (P<0.01) for Apoe(-/-) mice than in WT mice, and the aorta-to-blood ratio was 8-fold higher (P<0.001) for Zr-89-Mal-HSA compared with unspecific Zr-89-HSA. HSA-based probes were mainly distributed to the liver, spleen, kidneys, bone, and lymph nodes. The phosphor imaging autoradiography (PI-ARG) results corroborated the PET and gamma counter measurements, showing higher accumulation of Zr-89-Mal-HSA in the aortas of Apoe(-/-) mice than in WT mice (9.4 +/- 1.4 vs 0.8 +/- 0.3%; P<0.001). Conclusion: Zr-89 radiolabeling of Mal-HSA probes resulted in detectable activity in atherosclerotic lesions in aortas of Apoe(-/-) mice, as demonstrated by quantitative in vivo PET/MRI. Zr-89-Mal-HSA appears to be a promising diagnostic tool for the early identification of macrophage-rich areas of inflammation in atherosclerosis.
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| 6. |
- Andersen, Grethe Neumann, et al.
(författare)
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Assessment of vascular function in systemic sclerosis : indications of the development of nitrate tolerance as a result of enhanced endothelial nitric oxide production
- 2002
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 46:5, s. 1324-1332
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the relationship between endothelium-dependent and endothelium-independent functions and the stiffness of conduit arteries as well as levels of endothelial activation markers in patients with systemic sclerosis (SSc). METHODS: Endothelium-dependent (i.e., flow-mediated) and endothelium-independent (i.e., nitroglycerin-induced) dilation of the brachial artery was measured as the percentage of change from baseline (FMD% and NTG%, respectively) in 24 SSc patients and 24 age- and sex-matched healthy controls by high-resolution ultrasound imaging. The maximum increase in systolic pressure per unit of time (dP/dt(max)), as a measure of arterial wall stiffness, was assessed in the radial artery by pulse applanation tonometry. Plasma nitrate, the most important metabolite of nitric oxide, and 24-hour urinary excretion of nitrate were measured by gas chromatography mass spectrometry. Soluble E-selectin and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured by enzyme-linked immunosorbent assay. RESULTS: Brachial artery FMD% and NTG% did not differ between SSc patients and controls. Radial artery dP/dt(max) was significantly increased in the patients and correlated significantly with elevated levels of plasma nitrate and sVCAM-1. Twenty-four-hour urinary nitrate excretion tended to be elevated. Brachial artery NTG% was significantly inversely correlated with levels of plasma nitrate and soluble endothelial adhesion molecules. CONCLUSION: The ability of the brachial arteries to dilate in response to hyperemia and nitroglycerin challenge is preserved in SSc. Stiffness of the radial artery is increased, however. Endothelial activation seems to determine the extent of the brachial artery NTG% and the radial artery dP/dt(max). The data are compatible with the hypothesis that nitrate tolerance is present in the vascular smooth muscle cells of the brachial artery wall in SSc.
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| 7. |
- Andersen, Grethe Neumann, et al.
(författare)
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Correlation between increased nitric oxide production and markers of endothelial activation in systemic sclerosis : findings with the soluble adhesion molecules E-selectin, intercellular adhesion molecule 1, and vascular adhesion molecule 1
- 2000
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Ingår i: Arthritis and Rheumatism. - 0004-3591 .- 1529-0131. ; 43:5, s. 1085-1093
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Tidskriftsartikel (refereegranskat)abstract
- Objective To determine the relationship between vascular function and the inflammatory response in systemic sclerosis (SSc), and to investigate whether production of endothelial-derived nitric oxide (NO) is disturbed in this disease. Methods We measured plasma nitrate, urinary excretion of both nitrate and cGMP, and soluble adhesion molecules of endothelial origin in patients with SSc and in age- and sex-matched controls and compared these levels between groups. Additionally, we performed correlation analysis to determine how these variables were related to one another. Plasma nitrate and 24-hour-urinary excretion of nitrate in patients and controls were measured after a 72-hour nitrate-free-diet, using a gas chromatography/mass spectrometric method. Soluble adhesion molecules intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), and E-selectin and cytokines were measured by enzyme-linked immunosorbent assay. The expression of E-selectin was further investigated in skin biopsy specimens by immunoperoxidase staining, and the presence of inducible NO synthase by immunoblotting. Results Plasma nitrate and 24-hour-urinary-excretion of cGMP were significantly elevated in patients compared with controls, while 24-hour-urinary-excretion of nitrate tended to be elevated in SSc patients. Levels of sICAM-1, sVCAM-1, and sE-selectin were significantly elevated in the patients. Levels of plasma nitrate in the patients correlated significantly with levels of sVCAM-1 (P = 0.020) and sE-selectin (P = 0.018) and approached a significant correlation with sICAM-1 (P = 0.055), suggesting that activated endothelial cells may produce plasma nitrate. Conclusion NO synthesis is elevated in SSc patients, and the activated endothelial cell is a likely site of its production.
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| 8. |
- Andersson, Bert, 1952, et al.
(författare)
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An echocardiographic evaluation of patients with idiopathic heart failure.
- 1995
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Ingår i: Chest. - 0012-3692. ; 107:3, s. 680-9
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Tidskriftsartikel (refereegranskat)abstract
- The primary myocardial disease idiopathic dilated cardiomyopathy (IDCM) is not clearly defined in the literature. The description is both morphologic and etiologic. We examined consecutive patients with congestive heart failure (CHF) of unknown cause to identify possible cases of IDCM and to give a detailed description of echocardiographic data and possible diastolic dysfunction in this group. The hospital records of patients aged 16 to 65 years hospitalized due to CHF or IDCM during a 6-year period (N = 2,711) were evaluated in a defined region of western Sweden. Twenty-two percent (584/2,711) of these records contained no plausible cause of CHF or IDCM, and among patients being alive, obvious cause was lacking in 411 of 1,516 (27%). These 411 patients were offered a diagnostic investigation, including echocardiography, and they were compared with a randomly selected control group (n = 103) from the general population. Of 411 patients, 293 accepted investigation. From the control group, we defined the reference level for left ventricular (LV) dilatation to be > 32 mm/m2, and reduced ejection fraction according to Teichholz formula to be < 50%. Applying these borderlines, we identified LV dilatation and systolic dysfunction to be present in 30%, either dilatation or systolic dysfunction in 36%, and neither in 34%. In patients without any signs of systolic dysfunction 44% (26/59) showed signs of diastolic dysfunction. In a multivariate analysis, LV dimension was not independently correlated to disease, although LV dimension was univariately correlated to ejection fraction (EF) (r = -0.59; p < 0.0001). However, EF (p < 0.0001), left atrial dimension (p < 0.0001), and the first third filling fraction (p < 0.0001) were the constellation of parameters that most accurately separated patients from controls. By using these three parameters, a positive and negative predictive accuracy of 98% and 61%, respectively, was achieved. Thus, in a consecutive group of patients with idiopathic CHF recruited from a nonselected group of hospitalized patients with CHF, all grades of ventricular function were found. In this group, 30% were identified as having IDCM. We give reference values for the diagnosis of idiopathic IDCM and a simple tool to identify patients with systolic and diastolic dysfunction.
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| 9. |
- Andersson, Bert, 1952, et al.
(författare)
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Changes in early and late diastolic filling patterns induced by long-term adrenergic beta-blockade in patients with idiopathic dilated cardiomyopathy.
- 1996
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Ingår i: Circulation. - 0009-7322. ; 94:4, s. 673-82
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Tidskriftsartikel (refereegranskat)abstract
- beta-Blockers have been used in patients with idiopathic dilated cardiomyopathy to improve cardiac performance and theoretically would be beneficial to diastolic function. However, there are few reports on changes in diastolic function during chronic pharmacological treatment of congestive heart failure.The present study was a substudy in the international Metoprolol in Dilated Cardiomyopathy Trial. Transmitral Doppler echocardiography was used to evaluate diastolic function in 77 patients randomly assigned to placebo (n = 37) or metoprolol (n = 40). The patients were treated for 12 months. Changes in Doppler flow variables in the metoprolol group implied a less restrictive filling pattern, expressed as an increase in E-wave deceleration time (placebo, 185 +/- 126 to 181 +/- 64 ms; metoprolol, 152 +/- 63 to 216 +/- 78 ms; P = .01, placebo versus metoprolol). Maximal increase in deceleration time had occurred by 3 months, whereas systolic recovery was achieved gradually and maximal effect was seen by 12 months of treatment. Although deceleration time was correlated to heart rate at baseline, changes in deceleration time were not significantly correlated to changes in heart rate during treatment.During the first 3 months of treatment, maximal effects on diastolic variables were reached, whereas the most prominent effect on systolic function was seen late in the study. It is suggested that effects on diastolic filling account for subsequent later myocardial systolic recovery. The E-wave deceleration time, which in recent studies has been shown to be a powerful predictor of survival, was significantly improved in the metoprolol-treated patients.
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| 10. |
- Andersson, Bert, 1952, et al.
(författare)
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Early changes in longitudinal performance predict future improvement in global left ventricular function during long term beta adrenergic blockade.
- 2000
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Ingår i: Heart (British Cardiac Society). - 1468-201X. ; 84:6, s. 599-605
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Tidskriftsartikel (refereegranskat)abstract
- Contraction of longitudinal and subendocardial myocardial muscle fibres is reflected in descent of the atrioventricular (AV) plane. The aim was therefore to determine whether beta blocker treatment with prolongation of diastole might result in improved function as reflected by AV plane movements in patients with chronic heart failure.Double blind, randomised, placebo controlled and open intervention study.University hospital.Patients with congestive heart failure: placebo controlled (n = 26) and an open protocol (n = 15).12 months of metoprolol treatment.Short axis and long axis echocardiography, invasive haemodynamics, radionuclide angiography.Recovery of systolic and diastolic function during metoprolol treatment was reflected by early changes in mean (SD) AV plane amplitude, from 5.3 (2.0)% to 7.1 (3.2)% and 7.8 (3. 1)% (at 3 and 12 months, respectively; p < 0.05). In a multivariate analysis, only the change in AV plane amplitude by three months was independently associated with improvement in pulmonary capillary wedge pressure by six months (r = 0.80, p = 0.017). Change in AV plane amplitude by three months was also a better predictor of improvement in ejection fraction by 12 months (r = 0.78, p < 0.001) than changes in radionuclide ejection fraction by three months (r = 0.34, p = 0.049).Improvement in longitudinal contraction was closely associated with a decrease in left ventricular filling pressure during metoprolol treatment. This association was stronger than changes in short axis performance or radionuclide ejection fraction, emphasising the importance of AV plane motion for left ventricular filling and systolic performance in patients with heart failure.
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