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M Ostergaard

Publications and source records attributed to M Ostergaard.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Intra-articular glucocorticoid injections in joint diseases].

Intra-articular glucocorticosteroid injections are widely used in mono- or oligoarticular flares of patients with rheumatoid arthritis and other aseptic inflammatory joint diseases, as well as in osteoarthritis. Rapid and pronounced, but usually temporary, suppression of local joint inflammation may be achieved with only minor systemic effect. In osteoarthritis the effect is brief and transient. Triamcinolone hexacetonide provides the longest clinical effect, but since this drug may cause local tissue necrosis when injected outside a synovial cavity it should be used only by experienced clinicians. The risk of glucocorticoid-induced cartilage damage is discussed. The risk is probably less than that of untreated joint inflammation. Nevertheless, it is recommended that injections into the same joint are limited, for instance to one injection every six weeks and no more than three or four in one year. Furthermore, indications and contraindications should be carefully considered prior to each injection. Intra-articular glucocorticoid therapy may be of considerable clinical value in the management of aseptic arthritis, if administered on correct indications using a correct technique.

Anti-Inflammatory Agents↗
PubMed1999

A comprehensive protein resource for the study of bladder cancer: http://biobase.dk/cgi-bin/celis.

In our laboratories we are exploring the possibility of using proteome expression profiles of fresh bladder tumors (transitional cell carcinomas, TCCs; squamous cell carcinomas, SCCs) and random biopsies as fingerprints to subclassify histopathological types and as a starting point to search for protein markers that may form the basis for diagnosis, prognosis, and treatment. Ultimately, the goal of these studies is to identify signaling pathways and components that are affected at various stages of bladder cancer progression and that may provide novel leads in drug discovery. Here we present our ongoing efforts to establish comprehensive two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) databases of TCCs and SCCs which are being constructed based on the proteomic and immunohistochemical analysis of hundreds of fresh tumors, random biopsies and cystectomies received shortly after operation (http://biobase.dk/cgi-bin/celis).

Animals↗
PubMed1999

Psoriasin (S100A7): a putative urinary marker for the follow-up of patients with bladder squamous cell carcinomas.

To search for bladder squamous cell carcinoma markers that are released to the urine a blind and systematic analysis of the protein profiles of fresh tumors, their secreted proteins, as well as the patient's urine was carried out using state-of-the-art proteomic technology. We review the data concerning the putative marker psoriasin (S100A7), which, alone or in combination with other biomarkers, may be valuable for the noninvasive follow-up of patients bearing these tumors.

Biomarkers, Tumor↗
PubMed1999

Short-term culturing of low-grade superficial bladder transitional cell carcinomas leads to changes in the expression levels of several proteins involved in key cellular activities.

Fresh, superficial transitional cell carcinomas (TCCs) of low-grade atypia (3 grade I, Ta; 6 grade II, Ta), as well as primary cultures derived from them were labeled with [35S]methionine for 16 h, between 2 and 6 days after inoculation. Whole protein extracts were subjected to IEF (isoelectric focusing) two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) followed by autoradiography. Proteins were identified by a combination of proteomic technologies that included microsequencing, mass spectrometry, 2-D PAGE immunoblotting and comparison with the bladder TCC protein database available on the internet (http://biobase.dk/cgi-bin/celis). Comparison of the IEF 2-D gel protein profiles of fresh tumors and their primary cultures showed that the overall expression profiles were strikingly similar, although differing significantly in the levels of several proteins whose rate of synthesis was differentially regulated in at least 85% of the tumor/culture pairs as a result of the short-term culturing. Most of the proteins affected by culturing were upregulated and among them we identified components of the cytoskeleton (keratin 18, gelsolin and tropomyosin 3), a molecular chaperone (hsp 28), aldose reductase, GST pi, metastasin, synuclein, the calreticulin precursor and three polypeptides of unknown identity. Only four major proteins were downregulated, and these included two fatty acid-binding proteins (FABP:FABP5 and A-FABP) which are thought to play a role in growth control, the differentiation-associated keratin 20, and the calcium-binding protein annexin V. Proteins that were differentially regulated in only some of the cultured tumors included alpha-enolase, triosphosphate isomerase, members of the 14-3-3 family, hnRNPs F and H, PGDH, hsp (heat-shock protein) 60, BIP, the interleukin-1 receptor antagonist, the nucleolar protein B23, as well as several proteins of yet unknown identity. The suitability of in vitro bladder tumor culture models to study complex biological phenomena such as malignancy and invasion is discussed.

Carcinoma, Transitional Cell↗
PubMed1999

Magnetic resonance imaging-determined synovial membrane volume as a marker of disease activity and a predictor of progressive joint destruction in the wrists of patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint destruction in rheumatoid arthritis (RA). METHODS: Twenty-six patients with RA, randomized to receive disease-modifying antirheumatic drug (DMARD) therapy alone (11 patients) or DMARDs in combination with oral prednisolone (15 patients), were followed up for 1 year with contrast-enhanced MRI of the dominant wrist (months 0, 3, 6, and 12), conventional radiography (months 0 and 12), and clinical and biochemical examinations. Bone erosion (by MRI and radiography) and synovial membrane volumes (by MRI) were assessed. RESULTS: Significant synovial membrane volume reductions were observed after 3 and 6 months in the DMARD + prednisolone group, and after 6 and 12 months in the DMARD-alone group (P < 0.01-0.02, by Wilcoxon-Pratt analysis). The rate of erosive progression on MRI was highly correlated with baseline scores and, particularly, with area under the curve (AUC) values of synovial membrane volume (Spearman's sigma = 0.69, P < 0.001), but not with baseline or AUC values of local or global clinical or biochemical parameters, or with prednisolone treatment. In none of 5 wrists with baseline volumes <5 cm3, but in 8 of 10 wrists with baseline volumes > or =10 cm3, erosive progression was found by MRI and/or radiography, indicating a predictive value of synovial membrane volumes. MRI was more sensitive than radiography for the detection of progressive bone destruction (22 versus 12 new bone erosions). CONCLUSION: MRI-determined synovial membrane volumes are closely related to the rate of progressive joint destruction. Quantitative MRI assessment of synovitis may prove valuable as a marker of joint disease activity and a predictor of progressive joint destruction in RA.

Administration, Oral↗
PubMed1999

Proteomic strategies in bladder cancer.

Here we review our current strategy for identifying phenotypic changes in the urothelium of bladder cancer patients with invasive disease, using a combination of proteomic technologies and immunowalking. This approach, which in principle can be applied to the study of any type of bladder cancer, makes use of proteomic technologies (for more information see http://biobase.dk/cgi-bin/celis) to reveal and identify proteins that are differentially expressed in fresh tumors and normal urothelium. Thereafter, specific antibodies against the differentially expressed proteins are used (immunowalking) to stain serial cryostat sections of cystectomies obtained from tumor-bearing patients who have undergone removal of the bladder for invasive disease. Since bladder cancer is a field disease--that is, a large part of the bladder lining is involved-the urothelium of these patients is expected to exhibit a spectrum of abnormalities, ranging from early stages of transformation to invasive disease. Besides highlighting the problems one faces when applying powerful proteomic technologies to the study of heterogeneous biopsy material, these studies show that it is feasible to study bladder cancer under experimental conditions that closely resemble the in vivo situation.

Animals↗
PubMed1999

Finger joint synovitis in rheumatoid arthritis: quantitative assessment by magnetic resonance imaging.

OBJECTIVE: To assess quantitatively, by magnetic resonance imaging (MRI), the synovial membrane volume in second to fifth metacarpophalangeal (MCP) joints in patients with rheumatoid arthritis and healthy controls, and to compare the synovial membrane volumes with a more easily obtained semi-quantitative score for hypertrophic synovial membrane. PATIENTS AND METHODS: MCP joints of the dominant hand of 37 patients and five controls were examined clinically and by MRI. Laboratory assessments were performed. RESULTS: Median synovial membrane volumes were considerably larger in clinically active rheumatoid arthritis (RA) joints (e.g. 0.97 ml in the second MCP joint) than in clinically inactive joints (0.54 ml) and control joints (0.04 ml). Nevertheless, group distributions overlapped and marked volume differences were found within clinically uniform groups. The semi-quantitative score was highly correlated with the synovial volumes (Spearman rho = 0.79; P < 0.00001). Synovial membrane volumes were poorly related to the presence of rheumatoid factor and to laboratory markers of inflammation. CONCLUSION: These findings suggest that synovial membrane volumes, as determined by MRI, in finger joints are related to clinical signs of synovitis, but also that the volumes may vary more than what can be accounted for by the clinical appearances. A semi-quantitative score may be sufficient for more routine purposes.

Adult↗
PubMed1999

Wrist and finger joint MR imaging in rheumatoid arthritis.

PURPOSE: To elaborate the best MR imaging protocol for studies in rheumatoid arthritis (RA) and to evaluate the sensitivity and interobserver agreement with respect to detection of bone erosions (MR and radiography) and grading of synovial membrane hypertrophy (MR imaging only). MATERIAL AND METHODS: MR imaging and conventional radiography of wrist and metacarpophalangeal (MCP) joints were performed in 41 RA patients and 3 healthy controls. The following pulse sequences were applied: T1-weighted spin-echo (T1-SE) with and without contrast enhancement, T2-SE, T2-turbo-SE, T1-2D-FLASH, T1-3D-FLASH, fat-saturated-T1-SE, STIR and 3D-DESS. RESULTS: Bone erosions were found by MR compared to radiography in 261 versus 85 bones of the wrist (ratio 3.1) and 59 versus 21 MCP joint quadrants (ratio 2.81). MR and radiography interobserver agreements were both approximately 90%. Likewise, MR scored synovial membrane hypertrophy in wrist and MCP joints with a high interobserver agreement. The most informative MR sequence appeared to be contrast-enhanced T1-SE MR, preferably with fat saturation. A STIR sequence or T2-weighted fat saturation sequence was useful in screening for joint disease. CONCLUSION: The sensitivity of MR is superior to conventional radiography with respect to detection of bone erosions in wrist and MCP joints. The interobserver agreement for MR and radiography was similar. Thus, MR of wrist and finger joints may become a useful supplement to conventional radiography in the evaluation of RA patients in clinical trials and clinical practice.

Adult↗
PubMed1998

Human and mouse proteomic databases: novel resources in the protein universe.

Proteomics is an emerging area of research of the post-genomic era that deals with the global analysis of gene expression using a plethora of techniques to resolve (high resolution two-dimensional polyacrylamide gel electrophoresis, 2D PAGE), identify (peptide sequencing by Edman degradation, mass spectrometry, Western immunoblotting, etc.), quantitate and characterize proteins, as well as to store (comprehensive 2D PAGE databases), communicate and interlink protein and DNA sequence and mapping information from genome projects. Here we review the current status as well as applications of human and mouse proteomic 2D PAGE databases that are being systematically constructed for the global analysis of gene expression in both health and disease (http://biobase.dk/cgi-bin/celis). Furthermore, we discuss the problems one faces when using powerful proteomic technology to study heterogeneous tissue and tumor biopsies, and emphasize the importance of building comprehensive databases that contain a critical mass of information for both known and novel proteins in normal and disease conditions.

Animals↗
PubMed1998

Quantification of synovistis by MRI: correlation between dynamic and static gadolinium-enhanced magnetic resonance imaging and microscopic and macroscopic signs of synovial inflammation.

Dynamic and static gadolinium-diethylenetriaminepentaacetic acid(Gd-DTPA)-enhanced magnetic resonance imaging (MRI) were evaluated as measures of joint inflammation in arthritis, by a comparison with macroscopic and microscopic signs of synovitis. Furthermore, the importance of the size of the evaluated synovial areas was investigated, as was the optimal time for enhancement measurements. Seventeen rheumatoid arthritis knees and 25 osteoarthritis knees, scheduled for arthroscopy or arthrotomy, were included. Macroscopic and microscopic synovial inflammation as well as nine histologic tissue characteristics were graded at four preselected biopsy sites. Preoperative T1-weighted dynamic fast low angle shot and static spin-echo Gd-enhanced MRI were performed. The dynamic enhancement rate and the static enhancement were measured in the entire synovial membrane of a preselected slice as well as at the four biopsy sites, and compared to synovial pathology. The rate of early enhancement of the total synovial membrane of the preselected slice, determined by dynamic MRI, was highly correlated with microscopic evidence of active inflammation (Spearman p = 0.73; p < 10(-7). Dynamic MRI could distinguish knees with and without synovial inflammation with a high predictive value (0.81-0.90). Moderate and severe inflammation could not be differentiated. The early enhancement rate was correlated with histologic features of active inflammation, particularly vessel proliferation and mononuclear leucocyte infiltration. Dynamic evaluation of small synovial sections at the biopsy sites and static spin-echo MRI resulted in considerably weaker correlations to histologic inflammation than dynamic evaluation of the total synovium. The optimal time for enhancement measurements was one-half to one minute after Gd injection, as the highest correlation coefficients to histologic inflammation were observed in this interval. Dynamic MRI can be used to determine synovial inflammation. Evaluation of large synovial areas one-half to one minute after Gd injection best reflects joint inflammation.

Adult↗
PubMed1998

B-Cell lymphoma induction by akv murine leukemia viruses harboring one or both copies of the tandem repeat in the U3 enhancer.

Akv is an endogenous, ecotropic murine leukemia virus (MuLV) of the AKR strain. It has served as a prototype nonpathogenic or weakly pathogenic reference virus for studies of closely related potent lymphomagenic viruses such as the T-lymphomagenic SL3-3. We here report that Akv and an Akv mutant (Akv1-99) with only one copy of the 99-bp transcriptional enhancer induce malignant lymphomas with nearly 100% incidence and mean latency periods of 12 months after injection into newborn NMRI mice. Molecular analysis of tumor DNA showed that the majority of the tumors were of the B-cell type. Sequence analysis of proviral transcriptional enhancers in DNA of B-cell lymphomas revealed conservation of the enhancer sequence, as well as a lack of sequence duplications of the Akv1-99 variant, while the repeat copy number in Akv was subject to fluctuations. In support of a B-cell specificity of the Akv enhancer, a murine plasmacytoma cell line was found to sustain three- to fivefold-higher transient transcriptional activity upon the Akv and Akv1-99 enhancers than upon the enhancer of the T-lymphomagenic SL3-3 MuLV. Thus, the overall picture is that Akv MuLV possesses a B- lymphomagenic potential and that the second copy of the 99-bp sequence seems to be of minor importance for this potential. However, in one animal the lymphomas induced by Akv1-99 were of the T-cell type. Among the 24 tumors analyzed only this one harbored a clonal proviral integration in the c-myc locus. This provirus had undergone a duplication of a 113-bp sequence of the enhancer region, partly overlapping with the 99-bp repeat of Akv, as well as a few single nucleotide alterations within and outside the repeats. Taken together with previous studies, our results suggest that T- versus B-lymphomagenic specificity of the enhancer is governed by more than one nucleotide difference and that alterations in binding sites for transcription factors of the AML1 and nuclear-factor-1 families may contribute to this specificity.

3T3 Cells↗
PubMed1998

Intensive dynamic training for females with chronic neck/shoulder pain. A randomized controlled trial.

OBJECTIVES: To compare the clinical effectiveness of an intensive three-month training programme with a less intensive programme on females suffering from chronic neck/shoulder pain. STUDY DESIGN: A prospective observer-blinded clinical trial including 12-month pretreatment follow-up. SETTING: Patients were referred to the Departments of Rheumatology and Physical Medicine at Hvidovre Hospital by their general practitioners. Training was undertaken at a satellite clinic for physiotherapy of Hvidovre Hospital. SUBJECTS: Female patients aged 18-65 years suffering from chronic neck/shoulder pain for a minimum of six months. INTERVENTION: Patients were examined by a physician in order to exclude serious diseases. They were then randomized to either an intensive neck/shoulder training programme or a programme of lesser intensity but of similar duration. MAIN OUTCOME MEASURES: Scales measuring pain and activities of daily living (ADL) were used, and strength and endurance measurements of the cervical and shoulder muscles were carried out at baseline and completion of the study. Follow-up measurements were carried out by postal questionnaire at 6 and 12 months after inclusion, and included pain, ADL and treatment satisfaction measurements. RESULTS: Seventy-seven patients were included in the trial, of whom 27 (69%) completed the intensive programme and 25 (61%) the lighter programme. Forty-one (>80%) completed the follow-up questionnaires. The patients in the two groups did not differ with regard to age, pain, ADL scores and physical measurements prior to training. Patients in both groups that completed the trial demonstrated statistically significant improvements in nearly all of the outcome measurements at completion. ADL scores maintained statistical significance at 12 months in both groups, but pain scores were only significantly improved in the intensive group at 12 months follow-up. There was no statistically significant difference between groups regarding pain or ADL, but overall 50% of all patients showed improvement. CONCLUSIONS: The type of low-tech dynamic training used in either of our two programmes resulted in both subjective and objective improvements in patients suffering from chronic neck/shoulder pain, but there were no statistically significant differences in outcome between the two approaches. The subjective improvements were maintained throughout the follow-up period.

Activities of Daily Living↗
PubMed1997

[Reduced sense of taste as a complication of the laryngeal mask use].

We report a unilateral lingual nerve paralysis following the use of a laryngeal mask airway in a 73-year-old man with hypertrophy of the prostate undergoing a TUR-P. The operation was performed in general anaesthesia using propofol, fentanyl, alfentanil and ventilation with 100% oxygen. The operation was uncomplicated and had a duration of two hours and twenty minutes. A week later the patient perceived a reduced sense of taste. Six months later the situation was unaltered.

Aged↗
PubMed1997

Proteome profiling of bladder squamous cell carcinomas: identification of markers that define their degree of differentiation.

One hundred fifty fresh bladder tumors were analyzed blindly by two-dimensional PAGE in combination with proteome identification techniques (microsequencing and mass spectrometry) and immunofluorescence of cryostat sections. Of these, six showed protein expression patterns corresponding to squamous cell carcinomas (SCCs). All tumors were already invasive at the time of presentation, and in most cases, the histopathological grade could not be determined with certainty. The more differentiated of the tumors included SCC 589-1, a lesion showing extensive keratinization, and 536-1, a pure SCC that resembled normal skin growing invasively into the muscle. Both tumors expressed keratins 5, 6, 10, 14, 16, 17, and 20, as well as the differentiation-associated proteins psoriasin, psoriasis-associated fatty acid-binding protein (PA-FABP), and galectin 7. SCC 589-1, however, exhibited higher levels of keratin 10, PA-FABP, and galectin 7 and, in addition, expressed keratins 13, 15, and 19, which were not detected in the pure SCC. Involucrin, glutathione S-transferase pi, stratifin (14-3-3 sigma), and the SCC antigen 1, on the other hand, were less abundant in SCC 589-1. In comparison, less-differentiated tumors did not express keratin 10 and were characterized by a decreased expression of keratin 14, psoriasin, PA-FABP, galectin 7, and stratifin (14-3-3 sigma). Indeed, two of these lesions (553-1 and 651-1) could be readily lined up in order of decreasing degree of differentiation based on the expression of these markers. The degree of differentiation of the other two SCCs could not be assessed with certainty because they may represent special cases (SCC 646-1, solid tumor; SCC 485-1, special differentiation pattern). All six SCCs externalized psoriasin to the urine, supporting the contention that this protein, alone or in combination with other polypeptides, may represent a useful marker for the early detection of these lesions.

Biomarkers, Tumor↗
PubMed1997

[Volumes of synovial membrane and joint effusion determined by MR imaging. Markers of severity and/or activity in rheumatoid arthritis?].

Volumes of synovial membrane and joint effusion were determined by MRI in 36 knees with gonarthritis and five healthy knees. In 18 knees MRI was performed before and immediately after arthrocentesis. The difference between MRI-determined and syringe-determined volumes of aspirated joint fluid was 0-7 ml, median 2 ml, corresponding to 0-18%, median 7%, of the pre-aspiration effusion volume. Synovial membrane volumes, determined before and after arthrocentesis varied 0-10 ml, median 3 ml (0-17%, median 7%). No significant systematic misinterpretation of the borderline between joint fluid and synovium was found. The interobserver variation was < 15% in all measurements of synovial volumes > 10 ml and effusion volumes > 5 ml. Patient repositioning resulted in variations < 10%. The synovial volumes in clinically active, clinically inactive and healthy knees were statistically significantly different (median 79 ml, 21 ml and 3 ml, respectively). We conclude that effusion volumes, and in all probability also synovial membrane volumes, can be determined by MRI with a maximal error of approximately 20%. The synovial volume is related to the inflammatory activity of the joint. The results encourage further studies of the value of effusion and synovial membrane volumes as markers of the activity and/or severity of joint inflammation.

Arthritis, Rheumatoid↗
PubMed1997

Magnetic resonance imaging-determined synovial membrane and joint effusion volumes in rheumatoid arthritis and osteoarthritis: comparison with the macroscopic and microscopic appearance of the synovium.

OBJECTIVE: To evaluate the relationship between synovial membrane and joint effusion volumes determined by magnetic resonance imaging (MRI) and macroscopic and microscopic synovial pathologic findings in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Synovial biopsies were performed, and macroscopic grades of synovitis assigned, at preselected knee sites during arthroscopy or arthrotomy in 17 knees with RA and 25 with OA. Synovial inflammation and 9 separate tissue characteristics were graded histologically. Synovial membrane and joint effusion volumes were determined by preoperative MRI, enhanced with intravenous gadopentetate dimeglumine. RESULTS: MRI-determined synovial membrane volumes were correlated with the overall histologic assessment of synovial inflammation (Spearman's sigma = 0.55, P < 0.001), with fibrin deposition, with subsynovial mononuclear and polymorphonuclear leukocyte infiltration (sigma = 0.51-0.59), and less significantly with macroscopic synovitis, vessel proliferation, and granulation tissue formation (sigma = 0.40-0.42). No correlation with synovial lining multiplication, perivascular edema, villous formation, or fibrosis was found (sigma < 0.30). CONCLUSION: MRI-determined synovial volumes are correlated with synovial inflammatory activity. Synovial volumes probably mainly reflect the mass of cell-infiltrated, vascularized subsynovial tissue, but may also be influenced by the cumulative synovial proliferative activity. MRI-determined synovial membrane and effusion volumes may be sensitive markers and/or predictors of disease activity and treatment outcome in RA.

Adult↗
PubMed1997

Different approaches to synovial membrane volume determination by magnetic resonance imaging: manual versus automated segmentation.

Automated fast (5-20 min) synovial membrane volume determination by MRI, based on pre-set post-gadolinium-DTPA enhancement thresholds, was evaluated as a substitute for a time-consuming (45-120 min), previously validated, manual segmentation method. Twenty-nine knees [rheumatoid arthritis (RA) 13, osteoarthritis (OA) 16] and 17 RA wrists were examined. At enhancement thresholds between 30 and 60%, the automated volumes (Syn(x%)) were highly significantly correlated to manual volumes (SynMan) (knees: rho = 0.78-0.91, P < 10(-5) to < 10(-9); wrists: rho = 0.87-0.95, P < 10(-4) to < 10(-6)). The absolute values of the automated estimates were extremely dependent on the threshold chosen. At the optimal threshold of 45%, the median numerical difference from SynMan was 7 ml (17%) in knees and 2 ml (25%) in wrists. At this threshold, the difference was not related to diagnosis, clinical inflammation or synovial membrane volume, e.g. no systematic errors were found. The inter-MRI variation, evaluated in three knees and three wrists, was higher than by manual segmentation, particularly due to sensitivity to malalignment artefacts. Examination of test objects proved the high accuracy of the general methodology for volume determinations (maximal error 6.3%). Preceded by the determination of reproducibility and the optimal threshold at the available MR unit, automated 'threshold' segmentation appears to be acceptable when changes rather than absolute values of synovial membrane volumes are most important, e.g. in clinical trials.

Adult↗