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Biomedical subjects

M Ostergaard

Publications and source records attributed to M Ostergaard.

54 records · Page 3Linked to original sources
PubMed1997

Mapping of a major osteomagenic determinant of murine leukemia virus RFB-14 to non-long terminal repeat sequences.

Certain isolates of murine leukemia viruses (MuLVs) have, apart from a leukemogenic potential, the capability of inducing diseases of nonhematopoietic tissues in susceptible strains of mice. We have reported on the molecular cloning of a bone-tumorigenic virus, RFB-14 MuLV, which was found to induce benign bone tumors, osteomas, with 100% incidence in mice of the CBA/Ca strain (L. Pedersen, W. Behnisch, J. Schmidt, A. Luz, F. S. Pedersen, V. Erfle, and P. G. Strauss, J. Virol. 66:6186-6190, 1992). In order to analyze the bone tumor-inducing phenotype of RFB-14 MuLV, we have studied the pathogenic potential of recombinant viruses between RFB-14 and the nonosteomagenic, highly leukemogenic SL3-3 MuLV. The recombinants were constructed so as to reveal whether a major determinant of osteomagenicity maps to sequences within or outside the long terminal repeats (LTR). Our data show that a major determinant of the osteoma-inducing potential of RFB-14 MuLV maps to the non-LTR region of the genome. Furthermore, we demonstrate that a strong determinant of leukemogenicity is harbored by the non-LTR region of SL3-3 MuLV.

3T3 Cells↗
PubMed1996

Human 2-D PAGE databases for proteome analysis in health and disease: http://biobase.dk/cgi-bin/celis.

Human 2-D PAGE Databases established at the Danish Centre for Human Genome Research are now available on the World Wide Web (http://biobase.dk/cgi-bin/celis). The databanks, which offer a comprehensive approach to the analysis of the human proteome both in health and disease, contain data on known and unknown proteins recorded in various IEF and NEPHGE 2-D PAGE reference maps (non-cultured keratinocytes, non-cultured transitional cell carcinomas, MRC-5 fibroblasts and urine). One can display names and information on specific protein spots by clicking on the image of the gel representing the 2-D gel map in which one is interested. In addition, the database can be searched by protein name, keywords or organelle or cellular component. The entry files contain links to other databases such as Medline, Swiss-Prot, PIR, PDB, CySPID, OMIM, Methabolic pathways, etc. The on-line information is updated regularly.

Computer Communication Networks↗
PubMed1996

Loss of adipocyte-type fatty acid binding protein and other protein biomarkers is associated with progression of human bladder transitional cell carcinomas.

Multifocal recurrent papillary tumors provide a unique model system to study the molecular mechanisms underlying the steps involved in transitional cell carcinoma progression and offer a valuable source of material to search for biomarkers that may form the basis for diagnosis, prognosis, and treatment. We have examined the protein expression profiles of normal bladder urothelium and of 63 transitional cell carcinomas of various histopathological grades and T stages using high-resolution, two-dimensional gel electrophoresis, microsequencing, mass spectrometry, and a two-dimensional gel protein database approach for polypeptide identification (http://biobase.dk/cgi-bin/celis). In general, the results revealed a striking similarity between the overall qualitative expression patterns of papillary tumors of all grades, as well as of papillary and solid tumors of grade III. With few exceptions, tumors of grades I-III expressed, albeit at different levels, all of the keratins (7, 8, 13, 17, 18, 19, and 20) found in the normal urothelium. Grade IV tumors lacked or expressed reduced levels of keratin 13 but most resembled low-grade tumors. One invasive grade IV tumor, however, expressed a fibroblast-like protein phenotype. Four proteins that were expressed by normal urothelium and were lost at various stages of progression were identified as glutathione S-transferase mu, prostaglandin dehydrogenase (PGDH), a fatty acid binding protein with homology to the adipocyte isoform (A-FABP), and keratin 13. The percentage of tumors expressing A-FABP was very high in low-grade lesions but decreased drastically (P = 0.0006) in grade III and IV neoplasms. In addition, low-grade tumors contained more A-FABP than their high-grade counterparts. The stage of the disease was also statistically (P = 0.0269) related to the presence or absence of A-FABP in grade III tumors. Similar analysis of glutathione S-transferase mu and PGDH showed a statistically significant decrease of these proteins in high-grade (grades III and IV) tumors (P = 0.0026 and P = 0.0044, respectively). Only PGDH showed a suggestive correlation (P = 0.0775) with the stage of the disease in grade III tumors. Keratin 13 showed a drastic decrease in grade IV tumors. In addition to identifying biomarkers that may have prognostic value, our studies have suggested that A-FABP is an important component of the pathway(s) leading to bladder cancer development.

Biomarkers, Tumor↗
PubMed1996

Quantitative assessment of synovial inflammation by dynamic gadolinium-enhanced magnetic resonance imaging. A study of the effect of intra-articular methylprednisolone on the rate of early synovial enhancement.

The effect of temporary inflammatory suppression on synovial membrane enhancement, as determined by dynamic and static gadolinium-DTPA enhanced magnetic resonance imaging (MRI), was studied. MRI of 18 arthritic knees was performed before and 1, 7, 30 and 180 days after intra-articular methylprednisolone injection until clinical relapse. MRI of another six knees was performed twice within 2-4 days in order to assess interobserver and inter-MRI variation. The rate of early enhancement of the entire synovial membrane of a pre-selected central sagittal slice (REEsyn,tot), determined by dynamic T1-weighted FLASH MRI, decreased in all knees within the first post-treatment week and remained low during remission, although gradually increasing. In cases of clinical relapse, REEsyn,tot increased to pre-treatment levels. The interobserver plus inter-MRI variation was maximally 27%. The predictive values of a REEsyn,tot below/above 1.0%/s were 0.94 and 0.91, respectively, with respect to the absence/presence of clinical synovitis. Evaluation of small synovial areas revealed marked regional heterogeneity. Static spin echo MRI was not informative. The study indicates that the rate of early synovial enhancement reflects synovial inflammatory activity. Subclinical changes may be revealed. Evaluation of large synovial areas increases reproducibility and reduces the effect of regional heterogeneity. Dynamic MRI may prove a clinically useful measure of synovial inflammation.

Anti-Inflammatory Agents↗
PubMed1996

Quantitative assessment of the synovial membrane in the rheumatoid wrist: an easily obtained MRI score reflects the synovial volume.

Determination of the synovial membrane volume in the rheumatoid arthritis (RA) wrist by gadolinium-DTPA-enhanced MRI is introduced. Moreover, dynamic imaging and an MRI score of synovial hypertrophy, based on gradings in six regions, are evaluated as substitutes of the time-consuming volume calculations. Twenty-six RA wrists were examined. Synovial membrane volumes ranged from 1 to 20 ml (median 9 ml). Synovial hypertrophy scores were highly correlated to synovial volumes (Spearman r = 0.88; P < 10(-8) for uncorrelated values). The volumes and scores were significantly higher in wrists with joint swelling and/or joint tenderness than in wrists without these signs (Mann-Whitney, both P < 0.05). Suboptimal slice selection made dynamic imaging uninformative. MRI allows quantification of the synovial volume in the rheumatoid wrist. The volume is related to clinical signs of inflammation, but may also give information about the cumulated synovial proliferation in the joint. An easily obtained score of synovial hypertrophy reflects the synovial volume and may thus be a useful marker of synovial involvement.

Adult↗
PubMed1996

Changes in synovial membrane and joint effusion volumes after intraarticular methylprednisolone. Quantitative assessment of inflammatory and destructive changes in arthritis by MRI.

OBJECTIVE: To evaluate synovial membrane volumes, effusion volumes, and cartilage and bone erosion scores determined by magnetic resonance imaging (MRI) as markers of disease activity and severity in arthritis. METHODS: Gadolinium-DTPA enhanced MRI of 18 arthritic knees was performed before and 1, 7, 30 and 180 days after intraarticular methylprednisolone injection until clinical relapse. Intraobserver, interobserver, and inter-MRI variations were determined from 2 successive MRI of another 6 knees. RESULTS: In all knees synovial membrane and effusion volumes decreased within the first posttreatment week (median decrease 49 and 65%, respectively), and remained low during remission. Synovial volumes, but not effusion volumes, increased to pretreatment levels in case of clinical relapse, indicating that synovial volumes were most important to the clinical appearance. The intraobserver + interobserver + inter-MRI variation was maximally 26%. Total volumes and volumes in a selected sagittal slice were highly statistically correlated. The duration of clinical remission in patients with rheumatoid arthritis (RA) was significantly inversely correlated to the pretreatment synovial volume (both total and "one slice" volumes), but not to the effusion volume, MRI or radiography scores of erosions or any clinical/laboratory variables. Cartilage and bone erosions, invisible by radiography, were visualized by MRI. No progressive erosive changes were observed. CONCLUSION: MRI-determined synovial and effusion volumes and MRI scores of cartilage and bone erosions are reproducible and may be sensitive measures of disease activity and severity in RA. The synovial volume may rather than the effusion volume determine clinical appearance. Both are influenced by the present inflammatory activity. The pretreatment synovial volume may have predictive value to treatment outcome in RA.

Adult↗
PubMed1995

Effect of intraarticular osmic acid on synovial membrane volume and inflammation, determined by magnetic resonance imaging.

The changes in MR-determined synovial membrane volume, early synovial enhancement, and cartilage and bone erosions after osmic acid knee synovectomy were studied. Gadolinium-DTPA enhanced magnetic resonance imaging (MRI) of 18 knees with persistent arthritis was performed before and 1 month after treatment. The synovial membrane volume was significantly reduced (median -52%) in all 9 patients brought into clinical remission (p < 0.01), while no significant change was found in patients with clinical relapse. The early synovial enhancement was not significantly changed. MRI revealed progressive erosive changes in 2 patients. The time of relapse was correlated to a MR-erosion score, but not to early synovial enhancement or volumes of synovium or effusion (Spearman tests). MRI-determined synovial membrane volumes and early synovial enhancement may be objective quantitative markers of inflammation. MR-scores of cartilage and bone erosions are sensitive to progressive changes occurring within a month.

Adult↗
PubMed1995

The accuracy of MRI-determined synovial membrane and joint effusion volumes in arthritis. A comparison of pre- and post-aspiration volumes.

Magnetic resonance imaging (MRI) of 18 knees of patients with arthritis was performed before and immediately after arthrocentesis. Pre- and post-aspiration volumes were calculated by adding the outlined areas of synovium/effusion from a continuous series of gadolinium-DTPA-enhanced 5 mm transversal T1-weighted MR-images. 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. We conclude that effusion volumes and in all probability also synovial membrane volumes, can be determined by MRI with a maximal analytical error of approximately 20%. The acceptable accuracy of the method encourages further studies of the value of effusion and synovial membrane volumes as markers of the activity and/or severity of joint inflammation.

Adult↗
PubMed1995

Scoring of synovial membrane hypertrophy and bone erosions by MR imaging in clinically active and inactive rheumatoid arthritis of the wrist.

MRI-scores of synovial membrane hypertrophy and bone erosions of the RA-wrist are introduced. Gadolinium-DTPA enhanced magnetic resonance imaging (MRI) and conventional radiography (CR) of the wrist were performed in 16 patients with rheumatoid arthritis (RA) and 3 healthy controls. A MRI-score of synovial membrane hypertrophy was obtained by summation of gradings of synovial hypertrophy in 6 regions of the wrist. The score was significantly higher in wrists with than in wrists without clinical signs of active arthritis. The score was 0 in all healthy controls. Each bone of the wrist was assessed by MRI and CR with respect to bone erosions. Bone erosions were detected by MRI in 14 wrists in contrast to only 6 wrists by CR. In all patients the erosions were more numerous on MRI. The introduced methods may be useful quantitative measures of synovitis and early joint destruction in RA.

Adult↗
PubMed1995

Ultrasonography in arthritis of the knee. A comparison with MR imaging.

Ultrasonography (US) of the knee in gonarthritis was evaluated with gadolinium-DTPA-enhanced MR imaging as a reference. The study included 13 patients with gonarthritis, 2 patients with osteoarthritis and 5 healthy controls. Compared to MR, US identified 100% (12/12) of joint effusions, 100% (5/5) of Baker's cysts, 57% (8/14) of the synovial membranes of the suprapatellar recess and 38% (3/8) of bone erosions. No MR or clinical findings characterized the patients with ultrasonographically identifiable synovial membranes. Quantitative MR- and US-estimates of effusion, synovial membrane and cartilage thicknesses were correlated. The Spearman correlation coefficients were 0.87, 0.86 and 0.82, respectively. US reliably demonstrated joint effusions and Baker's cysts but showed lack of sensitivity for demonstration of the synovial membrane and bone erosions. When the synovial membrane was identifiable, the measurements of synovial thickness by US appeared precise. Cartilage evaluation by US seemed dependable. The clinical value was limited, because the weight-bearing areas were inaccessible.

Arthritis, Rheumatoid↗
PubMed1994

Synovial volume--a marker of disease severity in rheumatoid arthritis? Quantification by MRI.

Volumes of synovial membrane and joint effusion were determined by magnetic resonance imaging (MRI) in patients with inflammatory gonarthritis. Volumes were calculated by adding the outlined areas of synovium/effusion from a continuous series of gadolinium-DTPA-enhanced 5 mm transversal T1-weighted MR-images. Ten knees with clinically active gonarthritis (CAG), 8 knees with clinically inactive gonarthritis (CIG) and 5 healthy controls (HC) were examined. The synovial volume of CAG-, CIG- and HC-knees were significantly different. The median volumes were 79 ml, 21 ml and 3 ml, respectively. Synovial and effusion volumes were highly correlated. A selected sagittal one-slice volume showed a high correlation to the total volumes. The reliable quantification of synovial and effusion volumes could be useful in the assessment of disease severity and as an outcome measure to treatment.

Arthritis, Rheumatoid↗
PubMed1994

Dynamic gadolinium-enhanced MR imaging in active and inactive immunoinflammatory gonarthritis.

Dynamic T1-weighted FLASH MR imaging, obtained just after i.v. gadopentetate dimeglumine injection, and pre- and postcontrast T1-weighted spin-echo (T1-SE) MR imaging were performed to compare their information value with respect to inflammatory activity in immunoinflammatory gonarthritis. We examined 16 clinically active (CAG), 7 clinically inactive (CIG) and 4 healthy knees. The synovium of a preselected slice was outlined. Its area and relative signal intensity increase after gadopentetate dimeglumine on T1-SE and FLASH (at each time t) were calculated. The CAG knees showed a mean signal intensity increase on early dynamic FLASH images higher by far than the CIG knees, while no significant difference was found on spin-echo images obtained 5 to 15 min after contrast injection. The early signal enhancement probably reflects the perfusion and capillary permeability of the synovium. The area of synovium could differentiate between healthy and arthritic knees. Gadolinium-enhanced dynamic FLASH imaging may provide clinically useful information about the actual inflammatory activity of arthritic joints.

Adult↗
PubMed1992

[Pelvic insufficiency during pregnancy. Is pelvic girdle relaxation an unambiguous concept?].

Pelvic insufficiency during pregnancy, pelvic girdle relaxation, is defined as a condition with pain at the pubic symphysis and/or the sacroiliac joint developing in connection with pregnancy or delivery. No unambiguous criteria for the diagnosis of pelvic girdle relaxation exist but the following findings occur: Direct tenderness at the pubic symphysis and/or sacroiliac joint, waddling gait, pain on change of position, positive Trendelenburg's sign, iliac compression test, iliac gapping test and sacral pressure test. The frequency is 7.6-18.5 per 1000 deliveries. The incidence is increased in multiparae and women with occupations which strain the back. Recurrence occurs in 41-77%. The condition appears for the first time usually in the 5th-8th months of pregnancy. The majority of patients recover shortly after delivery but in some a condition of prolonged pain persists. The cause of pelvic girdle relaxation is unknown. Hormonal and biomechanical factors are considered to be of significance. No increased mobility in the pelvic joints nor general hypermobility have been demonstrated. Treatment is symptomatic and consists of information, instruction in relief and psychosocial support. Exercises and a trochanter belt may be useful. No controlled investigations of the value of treatment are available.

Back Pain↗
PubMedDate not supplied

Lack of postoperative pain relief after hysterectomy using preperitoneally administered bupivacaine.

BACKGROUND AND OBJECTIVES: It is well known that wound infiltration with local anesthetic can reduce postoperative pain in various degrees and with very few side effects. A previous study showed better analgesic effect when local anesthetic was applied in the subfascial, rather than the subcutaneous, layer. The present study investigated the effect of frequent bolus injections of bupivacaine (15 mL 2.5 mg/mL) preperitoneally through catheters placed intraoperatively in women who had undergone hysterectomy. METHODS: Postoperative pain and analgesic requirements were studied in a double-blind randomized trial including 41 patients. During surgery, the patients were randomized to one of two groups, and the investigators were blinded. Prior to closure of the peritoneum, the surgeon placed a catheter between the muscle layer and the peritoneum on each side of the wound. One group (n = 22) received bupivacaine (15 mL 2.5 mg/mL) every 4 hours for 48 hours via each catheter starting in the operating room. The placebo group (n = 19) received saline in a like manner. Postoperative pain was evaluated using a visual analog scale (VAS) and verbal rating scale (VRS) twice a day for 2 days at rest and on movement. Requirements of supplementary analgesics were monitored, as was wound infection after discharge. RESULTS: Bupivacaine administered preperitoneally did not improve analgesia at rest, during coughing, or during mobilization compared with saline. No difference between the groups was found regarding analgesic requirements. No complications of postoperative wound healing or toxic side effects were seen. CONCLUSION: Bolus injections of bupivacaine through intraoperative placed catheters did not improve analgesia postoperatively compared with saline injections.

Adult↗
PubMedDate not supplied

Drug survival and reasons for discontinuation of intramuscular methotrexate: a study of 212 consecutive patients switching from oral methotrexate.

OBJECTIVES: To assess the drug survival and reasons for discontinuation of intramuscular methotrexate (imMTX) in rheumatological patients who had switched to imMTX from oral methotrexate (oMTX). METHODS: Data from 212 consecutive patients who switched from oMTX to imMTX therapy at our outpatient clinic between April 1997 and January 2004 were collected retrospectively through survey of case records. Data included reason for discontinuation of oMTX, disease activity parameters, duration of imMTX therapy, and, in patients who withdrew, the reason for discontinuation of imMTX. RESULTS: The main reasons for switching from oMTX to imMTX were lack of efficacy (66%) and adverse events (28%). After 6 months, 114 patients (54%) were still receiving imMTX therapy, and their median serum C-reactive protein (CRP) and the percentage of patients who had received glucocorticoids during the previous 6 weeks had decreased (p<0.001). The median survival of imMTX therapy was 7.5 months (interquartile range 3-17). Twenty per cent of the patients received imMTX for more than 24 months. Of the 212 patients, 41% and 9% stopped imMTX therapy because of lack of efficacy and adverse events, respectively. Of the patients who had stopped oMTX because of adverse events, 22% also withdrew from imMTX because of adverse events. CONCLUSION: Half of the patients benefited from switching from oral to intramuscular methotrexate for at least 6 months, but only a minority adhered to the treatment for years. Lack of efficacy was the most frequent reason for discontinuation, while adverse events were rare.

Administration, Oral↗