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M Ostergaard

Publications and source records attributed to M Ostergaard.

At least 19 recordsLinked to original sources

Delayed gadolinium-enhanced magnetic resonance imaging (dGEMRIC) of hip joint cartilage: better cartilage delineation after intra-articular than intravenous gadolinium injection.

PURPOSE: To investigate and compare delayed gadolinium (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) in the hip joint using intravenous (i.v.) or ultrasound-guided intra-articular (i.a.) Gd-DTPA injection. MATERIAL AND METHODS: In 10 patients (50% males, mean age 58 years) with clinical and radiographic hip osteoarthritis (OA; Kellgren score II-III), MRI of the hip was performed twice on a clinical 1.5T MR scanner: On day 1, before and 90-180 min after 0.3 mmol/kg body weight i.v. Gd-DTPA and, on day 8, 90-180 min after ultrasound-guided i.a. injection of a 4 mmol/l Gd-DTPA solution. Coronal STIR, coronal T1 fat-saturated spin-echo, and a cartilage-sensitive gradient-echo sequence (3D T1 SPGR) in the sagittal plane were applied. RESULTS Both the post-i.v. and post-i.a. Gd-DTPA images showed significantly higher signal-to-noise (SNR) and contrast-to-noise (CNR) in the joint cartilage compared to the non-enhanced images (P < 0.002). I.a. Gd-DTPA provided significantly higher SNR and CNR compared to i.v. Gd-DTPA (P < 0.01). Furthermore, a better delineation of the cartilage in the synovial/cartilage zone and of the chondral/subchondral border was observed. CONCLUSION: The dGEMRIC MRI method markedly improved delineation of hip joint cartilage compared to non-enhanced MRI. The i.a. Gd-DTPA provided the best cartilage delineation. dGEMRIC is a clinically applicable MRI method that may improve identification of early subtle cartilage damage and the accuracy of volume measurements of hip joint cartilage.

Adult↗

Cardiac output--pulse contour analysis vs. pulmonary artery thermodilution.

BACKGROUND: The aims of this study were to determine the agreement between pulmonary artery thermodilution (PA-TD), transpulmonary thermodilution (TP-TD) and the pulse contour method, and to test the ability of the pulse contour method to track changes in cardiac output. METHODS: Cardiac output was determined twice before cardiac surgery with both PA-TD and TP-TD. The precision (two standard deviations of the difference between repeated measurements) and agreement of the two methods were calculated. Post-operatively, cardiac output was determined with the PA-TD and pulse contour methods, and the bias and limits of agreement were again calculated. Finally, in patients with heart rates below 60 beats/min or a cardiac index of less than 2.5 l/min/m2, atrial pacing was started and the haemodynamic consequences were monitored with the PA-TD and pulse contour methods. RESULTS: Twenty-five patients were included. The precisions of PA-TD and TP-TD were 0.41 l/min [95% confidence interval (CI), +/- 0.07] and 0.48 l/min (95% CI, +/- 0.08), respectively. The bias and limits of agreement between PA-TD and TP-TD were - 0.46 l/min (95% CI, +/- 0.11) and +/- 1.10 l/min (95% CI, +/- 0.19), respectively. Post-operatively, the bias and limits of agreement between the PA-TD and pulse contour methods were 0.07 l/min and +/- 2.20 l/min, respectively. The changes in cardiac output with atrial pacing were in the same direction and of the same magnitude in 15 of the 16 patients. CONCLUSION: The precision of cardiac output measurements with PA-TD and TP-TD was very similar. The transpulmonary method, however, overestimated the cardiac output by 0.46 l/min. Post-operatively, cardiac output measurements with the PA-TD and pulse contour methods did not agree, but the pulse contour method reliably tracked pacing-induced changes in cardiac output.

Adult↗

Routine database registration of biological therapy increases the reporting of adverse events twentyfold in clinical practice. First results from the Danish Database (DANBIO).

OBJECTIVE: To present from the Danish Database for Biological Therapies in Rheumatology (DANBIO) the frequencies and types of adverse events as well as risk factors during treatment with biological agents in clinical practice. METHODS: Adverse events during the first 2 years of clinical use of biological agents in Denmark were reported to the nationwide DANBIO and compared to the mandatory reports to the Danish Medicines Agency. RESULTS: Almost 90% of the patients treated with biological agents were registered in the DANBIO, and the database picked up 20 times as many adverse events as the Danish Medicines Agency. Infections and hypersensitivity reactions were the most prevalent adverse events. Age, disease duration, and previous number of disease-modifying anti-rheumatic drugs (DMARDS) were found to be risk factors for bacterial infections. CONCLUSION: A routine-based Danish database for biological therapies covers approximately 90% of patients and improves the reporting of adverse events.

Adult↗

Precision of bolus thermodilution cardiac output measurements in patients with atrial fibrillation.

BACKGROUND: The precision of bolus thermodilution cardiac output measurements in patients with atrial fibrillation (AF) has not previously been determined. A priori we suspected that the precision would be lower in patients with AF than in patients with sinus rhythm (SR). Consequently, we also determined if the precision could be improved by injecting the thermal indicator into the right ventricle instead of the right atrium. METHODS: Cardiac output was determined as the average result of four injections of 10 ml of iced saline. Replicate measurements were performed with thermal indicator injections into the right atrium and ventricle. The coefficients of variation and the precisions were calculated. RESULTS: In the 25 patients with AF, mean cardiac output was 3.96 l min(-1) (range 2.4-7.4), the coefficient of variation 0.073 (95% CI +/- 0.011), and the precision 0.38 l min(-1) (95% CI +/- 0.14) with injection into the right atrium. In the 25 patients with SR, mean cardiac output was 4.73 l min(-1) (range 2.4-7.3), the coefficient of variation 0.047(95% CI +/- 0.006), and the precision 0.38 l min(-1) (95% CI +/- 0.14). In both groups, an agreement analysis demonstrated that the injection of indicator into the right ventricle resulted in a significantly higher cardiac output [AF+0.25 (95% CI +/- 0.15) l min(-1), SR+0.29 ( +/- 0.20) l min(-1)]. CONCLUSION: The coefficient of variation for cardiac output determinations is 55% higher in patients with AF. Two measurements, separated by time or intervention, must differ by 15% in AF patients and 9% in SR patients before one can be 95% confident that a real change has taken place.

Aged↗

Power Doppler ultrasonography for assessment of synovitis in the metacarpophalangeal joints of patients with rheumatoid arthritis: a comparison with dynamic magnetic resonance imaging.

OBJECTIVE: To evaluate the effectiveness of power Doppler ultrasonography (PDUS) for assessing inflammatory activity in the metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA), using dynamic magnetic resonance imaging (MRI) as a reference method. METHODS: PDUS and dynamic MRI were performed on 54 MCP joints of 15 patients with active RA and on 12 MCP joints of 3 healthy controls. PDUS was performed with a LOGIQ 500 unit by means of a 7-13-MHz linear array transducer. Later the same day, MRI was performed with a 1.0T MR unit. A series of 24 coronal T1-weighted images of the second through the fifth MCP joints was obtained, with intravenous injection of gadolinium diethylenetriaminepentaacetic acid after the fourth image (dynamic MRI). From the MR images, the rate of early synovial enhancement (RESE; defined as the relative enhancement per second during the first 55 seconds postinjection) was calculated and compared with the flow signal on PDUS, which was scored as present or absent. RESULTS: In RA patients, flow signal on PDUS was detected in 17 of 54 MCP joints examined. Postcontrast MR images revealed an RESE of > or = 1.0%/second in 18 of 54 RA MCP joints. PDUS showed no flow in 47 of 48 MCP joints with an RESE of <1.0%/second and revealed flow in 16 of 18 MCP joints with an RESE of > or = 1.0%/second. Using dynamic MRI as a reference, PDUS had a sensitivity of 88.8% and a specificity of 97.9%. CONCLUSION: PDUS was reliable for assessing inflammatory activity in the MCP joints of RA patients, using dynamic MRI as the standard. PDUS and clinical assessment of joint swelling/tenderness were only weakly correlated.

Adult↗

Studies on YKL-40 in knee joints of patients with rheumatoid arthritis and osteoarthritis. Involvement of YKL-40 in the joint pathology.

OBJECTIVE: The presence of YKL-40 (human cartilage glycoprotein 39) in synovium, cartilage and synovial fluid (SF) from knee joints of patients with rheumatoid arthritis and osteoarthritis (OA) were related to histopathological changes in synovium and cartilage and to serum YKL-40 and other biochemical markers. METHODS: The localization of YKL-40 in synovium and cartilage was determined by immunohistochemistry. Synovial inflammation was estimated histologically and by magnetic resonance imaging (MRI). Biochemical markers of inflammation, neutrophil activation and cartilage metabolism were analysed. YKL-40 concentrations in serum and SF were determined by RIA and ELISA. RESULTS: In the synovium YKL-40 positive cells were found in lining and stromal cells (macrophages) and the number of YKL-40 positive cells was related to the degree of synovitis. In arthritic cartilage, YKL-40 was located to chondrocytes. YKL-40 levels in SF were higher in RA patients with moderate/severe or none/slight synovitis of the knee joint compared to OA patients with moderate/severe or none/slight synovitis. SF YKL-40 correlated with the synovial membrane and the joint effusion volumes determined by magnetic resonance imaging (MRI) and with other biochemical markers of intercellular matrix metabolism. SF YKL-40 was higher than serum YKL-40, and a relationship existed between the YKL-40 levels in SF and serum. Intraarticular glucocorticoid injection was followed by clinical remission and a decrease in serum YKL-40, which increased again at clinical relapse. CONCLUSIONS: YKL-40 in SF is derived from cells in the inflamed synovium, chondrocytes and SF neutrophils. Joint derived YKL-40 influences serum YKL-40. YKL-40 may be involved in the pathophysiology of the arthritic processes and reflect local disease activity.

Adipokines↗

Quantitative magnetic resonance imaging as marker of synovial membrane regeneration and recurrence of synovitis after arthroscopic knee joint synovectomy: a one year follow up study.

OBJECTIVES: By repeated magnetic resonance imaging (MRI) to study synovial membrane regeneration and recurrence of synovitis after arthroscopic knee joint synovectomy in patients with rheumatoid arthritis (RA) and other (non-RA) causes of persistent knee joint synovitis. METHODS: Contrast enhanced MRI was performed in 15 knees (nine RA, six non-RA) before and one day, seven days, two months, and 12 months after arthroscopic synovectomy. Synovial membrane volumes, joint effusion volumes, and cartilage and bone destruction were assessed on each MRI set. Baseline microscopic and macroscopic assessments of synovitis and baseline and follow up standard clinical and biochemical examinations were available. RESULTS: Synovial membrane and joint fluid volumes were significantly reduced two and 12 months after synovectomy. However, MRI signs of recurrent synovitis were already present in most knees at two months. No significant differences between volumes in RA and non-RA knees were seen. Synovial membrane volumes at two months were significantly inversely correlated with the duration of clinical remission, for all knees considered together (Spearman's correlation r(s)=-0.67; p<0.05), for RA knees (r(s)=-0.76; p<0.05), and for non-RA knees (r(s)=-0.83; p<0.05). Baseline volumes were not significantly correlated with clinical outcome. Only three knees (all RA) showed erosive progression. The rate of erosive progression was not correlated with MRI volumes or with clinical or biochemical parameters. CONCLUSION: The synovial membrane had regenerated two months after arthroscopic knee joint synovectomy and despite significant volume reductions compared with baseline it often showed signs of recurrent synovitis. MRI seems to be valuable as a marker of inflammation, destruction and, perhaps, as a predictor of therapeutic outcome in arthritis.

Adult↗

Interreader agreement in the assessment of magnetic resonance images of rheumatoid arthritis wrist and finger joints--an international multicenter study.

Magnetic resonance imaging (MRI) allows direct visualization of inflammation and destruction in rheumatoid arthritis (RA) joints. However, MRI scoring methods have not yet been standardized or appropriately validated. Our aim was to examine interreader agreement for a simple system of scoring RA changes on MRI among 5 centers that had not undertaken intergroup calibration. MRI of RA wrist and metacarpophalangeal (MCP) joints were scored by experienced readers in 5 centers in different countries. In substudy 1, 5 sets of 2nd-5th MCP joints from UK [Technique A: 1.5 T, coronal and axial T1 and T2 spin-echo, -/+ fat saturation (FS), -/+ iv gadolinium (Gd)] were scored for synovitis (score 0-3) and bone lesions (0-3). In substudy 2, we evaluated 19 sets of 2nd-5th MCP joints [10 sets from UK (Technique A) and 9 sets from the US (Technique B: 1.5 T; coronal T1 spin-echo and T2* gradient-echo + FS, no Gd)] and 19 wrist joints [9 from the US (Technique B) and 10 from Denmark (Technique C: 1.0 T; coronal and axial T1 spin-echo, no FS, -/+ Gd)]. Synovitis (0-3), bone lesions (0-3), and joint space narrowing (JSN, 0-3) were scored in each MCP joint and in 3 different regions of the wrist. Bone erosions and lesions in each bone were scored 0-5. Substudy 1 served to test and redesign the score sheets. In substudy 2, the scores of synovitis and bone lesions by the 5 groups were the same or differed by only one grade in 73% and 85% of joints, respectively. On MRI that included 2 imaging planes and iv Gd (Techniques A and C), these rates were 86% (synovitis) and 97% (bone lesions). Corresponding intraclass correlation coefficients (quadratic weighted kappas) were 0.44-0.68, mean 0.58 (synovitis), and 0.44-0.69, mean 0.62 (bone lesion), i.e., in the moderate to good range. Unweighted kappa values were in the low to moderate range, generally lowest for JSN (< 0.20), better for synovitis and bone erosions, and best for bone lesions, being generally highest for MRI with 2 planes pre- and post-Gd and in MCPjoints compared with wrists. These preliminary results suggest that the basic interpretation of MRI changes in RA wrist and MCP joints is relatively consistent among readers from different countries and medical backgrounds, but that further training, calibration, and standardization of imaging protocols and grading schemes will be necessary to achieve acceptable intergroup reproducibility in assessing synovitis and bone destruction in RA multicenter studies.

Arthritis, Rheumatoid↗

Magnetic resonance imaging in rheumatoid arthritis: summary of OMERACT activities, current status, and plans.

Complementing the 3 papers that precede it, this paper explains the rationale for the activities of an OMERACT working party on magnetic resonance imaging (MRI) evaluation of rheumatoid arthritis (RA), sets out provisional recommendations for the acquisition and scoring of MRI of the hand and wrist in RA, and delineates some of the many residual problems that need to be addressed.

Arthritis, Rheumatoid↗

Gene expression profiling: monitoring transcription and translation products using DNA microarrays and proteomics.

Novel and powerful technologies such as DNA microarrays and proteomics have made possible the analysis of the expression levels of multiple genes simultaneously both in health and disease. In combination, these technologies promise to revolutionize biology, in particular in the area of molecular medicine as they are expected to reveal gene regulation events involved in disease progression as well as to pinpoint potential targets for drug discovery and diagnostics. Here, we review the current status of these technologies and highlight some studies in which they have been applied in concert to the analysis of biopsy specimens.

Animals↗

[Magnetic resonance imaging as a marker of inflammation, destruction and prognosis in rheumatoid arthritis wrists].

To evaluate MRI for assessment of inflammation, destruction and prognosis in rheumatoid arthritis (RA), 26 RA patients, randomized to disease-modifying anti-rheumatic drug (DMARD) therapy alone or in combination with oral prednisolone, were followed for one year with contrast-enhanced MRI of the dominant wrist (months zero, three, six and 12), conventional radiography and clinical and biochemical examinations. Significant synovial membrane volume reductions were observed in both groups, earliest in the DMARD + prednisolone group. The rate of erosive progression on MRI was highly correlated with baseline and area-under-curve (AUC)-values of synovial membrane volume, but not with baseline or AUC-values of local or global clinical or biochemical parameters, nor with +/- prednisolone. MRI was more sensitive than radiography as regards detection of progressive bone destruction (22 versus 12 new bone erosions). MRI may prove valuable as marker of joint disease activity and destruction and, perhaps, prognosis in RA.

Adult↗

Bladder squamous cell carcinoma biomarkers derived from proteomics.

Proteomics provide powerful technology for analyzing the expression levels of thousands of proteins simultaneously both in health and disease. Here, we review proteomic strategies that we have developed to identify metaplastic lesions in bladder squamous cell carcinomas as well as biomarkers in the urine for follow-up studies of squamous cell carcinoma (SCC)-bearing patients.

Biomarkers, Tumor↗

Dynamic magnetic resonance imaging of the metacarpophalangeal joints in rheumatoid arthritis, early unclassified polyarthritis, and healthy controls.

OBJECTIVE: To introduce dynamic magnetic resonance imaging (MRI) as an indicator of inflammatory activity in the metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA) or early unclassified polyarthritis, and to compare the results with a healthy control group. MATERIALS AND METHODS: We examined 42 RA and 23 early unclassified polyarthritis patients, and 12 healthy controls in a cross-sectional study. Dynamic MRI (repeated FLASH-MR images after injection of a contrast agent) was performed through the 2nd to the 5th MCP joint. Two methods for identification of the enhancing synovial membrane were compared: 1) outlining of enhancing synovial membrane on subtraction images and 2) automated recognition by principal component analysis (PCA). The early enhancement (EE) rate was calculated on the basis of the first method. RESULTS: Method 1) and 2) were closely associated (P<0.00001). From the healthy control group, an upper limit (mean+2SD) of normal enhancement was established for the 2nd to 5th MCP joints, which served to identify abnormal EE rates in the corresponding joints of patients. The patients had higher EE rates in the 2nd to 5th MCP joints than had the healthy controls (P<0.01). There were no significant differences between the two patient groups (P>0.09). CONCLUSION: PCA seems to be a promising method for automated identification of enhancing tissue. EE rates of the finger joints may be useful in the assessment of the inflammatory activity in the joints of patients with RA and early unclassified polyarthritis and may reflect other aspects of disease activity than clinical evaluation.

Adult↗

Magnetic resonance imaging, radiography, and scintigraphy of the finger joints: one year follow up of patients with early arthritis. The TIRA Group.

OBJECTIVES: To evaluate synovial membrane hypertrophy, tenosynovitis, and erosion development of the 2nd to 5th metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints by magnetic resonance imaging in a group of patients with rheumatoid arthritis (RA) or suspected RA followed up for one year. Additionally, to compare the results with radiography, bone scintigraphy, and clinical findings. PATIENTS AND METHODS: Fifty five patients were examined at baseline, of whom 34 were followed up for one year. Twenty one patients already fulfilled the American College of Rheumatology (ACR) criteria for RA at baseline, five fulfilled the criteria only after one year's follow up, whereas eight maintained the original diagnosis of early unclassified polyarthritis. The following MRI variables were assessed at baseline and one year: synovial membrane hypertrophy score, number of erosions, and tenosynovitis score. RESULTS: MRI detected progression of erosions earlier and more often than did radiography of the same joints; at baseline the MRI to radiography ratio was 28:4. Erosions were exclusively found in patients with RA at baseline or fulfilling the ACR criteria at one year. At one year follow up, scores of MR synovial membrane hypertrophy, tenosynovitis, and scintigraphic tracer accumulation had not changed significantly from baseline; in contrast, swollen and tender joint counts had declined significantly (p<0.05). CONCLUSIONS: MRI detected more erosions than radiography. MR synovial membrane hypertrophy and scintigraphy scores did not parallel the changes seen over time in clinically assessed swollen and tender joint counts. Although joint disease activity may be assessed as quiescent by conventional clinical methods, a more detailed evaluation by MRI may show that a pathological condition is still present within the synovium.

Adult↗

Characterization of three hairy cell leukemia- derived cell lines (ESKOL, JOK-1, and hair-M) by multiplex-FISH, comparative genomic hybridization, FISH, PRINS, and dideoxyPRINS.

Hairy cell leukemia (HCL) is a chronic B-lymphocyte leukemia. Due to the proliferative inertia of the malignant cells, HCL-derived cell lines are an important tool for studies on this disease. We have elaborated the karyotypes of three HCL-derived cell lines, ESKOL, JOK-1, and Hair-M, by combining a range of molecular cytogenetic techniques, including multiplex (multicolor) fluorescence in situ hybridization (M-FISH), comparative genomic hybridization (CGH), conventional FISH, primed in situ labeling (PRINS), and dideoxyPRINS. We found ESKOL to be monoclonal with a single chromosome aberration, der(7)t(3;7)(q26.3;q31). JOK-1 also appeared to be monoclonal, having the karyotype 48,XY,der(4) t(1;4)(1pter-->p32::4qter-->pter), der(6)(6qter-->p22::q12--> qter), +der(7)t(7;11)(7pter-->q21::11p15-->pter),der(8)t(5;8;12) (5pter-->p14::12p11.2-->p12::8q12-->q21::8?cen-->-->24 .?2), der(14)t(8;14)(8qter-->q24.?2::14q32.3-->pter),+20. These karyotypes differ from the original descriptions of ESKOL and JOK-1. The Hair-M cells analyzed by us were found to be peritetraploid with numerous chromosomal rearrangements. The cell line was also found to be multiclonal. On this basis, we do not regard the Hair-M cell line to be suitable for HCL studies.

Aged↗

Proteomics and immunohistochemistry define some of the steps involved in the squamous differentiation of the bladder transitional epithelium: a novel strategy for identifying metaplastic lesions.

Here, we present a novel strategy for dissecting some of the steps involved in the squamous differentiation of the bladder urothelium leading to squamous cell carcinomas (SCCs). First, we used proteomic technologies and databases (http://biobase.dk/cgi-bin/celis) to reveal proteins that were expressed specifically by fresh normal urothelium and three SCCs showing no urothelial components. Thereafter, antibodies against some of the differentially expressed proteins as well as a few known keratinocyte markers were used to stain serial cryostat sections (immunowalking) of biopsies obtained from bladder cystectomies of two of the SCC-bearing patients (884-1 and 864-1). Because bladder cancer is a field disease, we surmised that the urothelium of these patients may exhibit a spectrum of abnormalities ranging from early metaplastic stages to invasive disease. Immunohistochemical analysis revealed three types of non-keratinizing metaplastic lesions (types 1-3) that did not express keratins 7, 8, 18, and 20 (expressed by normal urothelium) and could be distinguished based on their staining with keratin 19 antibodies. Type 1 lesions showed staining of all cell layers in the epithelium (with differences in the staining intensity of the basal compartment), whereas type 2 lesions exhibited mainly basal cell staining. Type 3 lesions did not stain with keratin 19 antibodies. In cystectomy 884-1, type 3 lesions exhibited the same immunophenotype as the SCC and may be regarded as precursors to the tumor. Basal cells in these lesions did not express keratin 13, suggesting that the tumor, which was also keratin 13 negative, may have arisen from the expansion of these cells. Similar results were observed with cystectomy 864-1, which showed carcinoma in situ of the SCC type. SCC 864-1 exhibited both keratin 19-negative and -positive cells, implying that the tumor arose from the expansion of the basal cell compartment of type 2 and 3 lesions. Besides providing with a novel strategy for revealing metaplastic lesions, our studies have shown that it is feasible to apply powerful proteomic technologies to the analysis of complex biological samples under conditions that are as close as possible to the in vivo situation.

Biomarkers, Tumor↗