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Biomedical subjects

B Swoboda

Publications and source records attributed to B Swoboda.

At least 19 recordsLinked to original sources

[Imaging of osteoarthritis of the peripheral joints].

Pain and loss of function are the clinical signs of osteoarthritis (OA). Conventional x-rays confirm the diagnosis or provide important hints for differential diagnosis. In the natural course of OA, x-rays are performed at longer intervals when pain increases or therapy is without effect, especially if more invasive therapies, or even surgery, becomes necessary. The advantages of x-rays are worldwide availability, cost effectiveness, very long experience with this imaging method and the possibility of storing the images for long periods of time. The typical findings of OA can be detected only roughly by quantitative methods. In many patients, grading of OA does not correlate well with the clinical symptoms. X-ray changes are part of the American College of Rheumatology (ACR) classification criteria for OA of the hand, hip and knee. Ordinary s-rays can depicting bone with a higher local resolution than any other imaging technique. Soft tissues and cartilage can be visualized only indirectly. In OA, ultrasound is the method to depict intra-articular effusion at an early stage. Osteophytes or the degree of synovitis are also visible. Concomitant changes in tendons, bursae or cartilage, such as structures in the hip, shoulder and knee, can be evaluated. MRI is an appropriate tool for describing changes in cartilage volume and concomitant soft-tissue alterations. For qualitative cartilage imaging, MRI has, to date, not been fully validated. Bone scans (bone scintigraphy) allow the differentiation of inflammatory from degenerative joint affections and may add information on the activity of the subchondral bone, which may develop to a prognostic marker of OA. This survey represents recommendations of the Commission "Imaging Techniques" of the German Rheumatology Society regarding the technical and individual conditions, indications, practical guidance and the typical findings of imaging in OA.

Arthrography↗

[Insoles for the rheumatic foot. A clinical and pedobarographic analysis].

BACKGROUND: Insoles are regarded as an appropriate tool for the management of rheumatic foot disorders. However, a quality control for this purpose has not been established. In our study, the clinical effectiveness of insoles used in patients with rheumatic foot disorders was addressed. In addition, we sought to establish pedobarography as a means of quality control for orthotic management of the rheumatic foot. MATERIAL AND METHODS: Our study included 20 rheumatoid arthritis patients with painful rheumatic foot deformities who were provided with insoles. Clinical data were obtained by physical examination and a 100-mm pain scale. Pedobarography was performed using the novel pedar cable system with new and individually designed insoles and after a 6-month follow-up. A shoe-only trial served as control. The parameters maximum force, peak pressure, force-time integral, and average pressure were analyzed in anatomical regions and an individually defined overloaded forefoot region. RESULTS: Clinical improvement was significant after a 6-month follow-up in spite of a heterogeneous group of patients. However, our results could not confirm consistent changes in plantar pressure distribution. CONCLUSION: As a conclusion, further efforts are necessary to establish a quality control for orthotic management of the rheumatic foot.

Adult↗

[Talonavicular arthrodesis for the rheumatoid foot].

BACKGROUND: Talonavicular joint fusion has been successfully applied for the surgical treatment of the rheumatoid foot. Several fixation techniques have been suggested for this purpose, however, with high rates of non-union. METHODS: Based on seven cases operated in our division, talonavicular joint fusion with two 3.5 mm compression screws and autologous bone grafting is discussed. Pain in the operated foot under weight-bearing conditions was assessed before surgery and after a mean follow-up of 35 months (range 3-58 months). RESULTS: Solid talonavicular fusion was achieved clinically and radiologically in all patients after 12 weeks. The surgery-related morbidity was low. At follow-up, weight-bearing pain was diminished compared to the preoperative status. CONCLUSIONS: Compression screw arthrodesis of the talonavicular joint in combination with autologous bone grafting is highly successful in rheumatoid arthritis patients.

Adult↗

EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

OBJECTIVE: To develop evidence based recommendations for the management of hip osteoarthritis (OA). METHODS: The multidisciplinary guideline development group comprised 18 rheumatologists, 4 orthopaedic surgeons, and 1 epidemiologist, representing 14 European countries. Each participant contributed up to 10 propositions describing key clinical aspects of hip OA management. Ten final recommendations were agreed using a Delphi consensus approach. Medline, Embase, CINAHL, Cochrane Library, and HTA reports were searched systematically to obtain research evidence for each proposition. Where possible, outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. Effect size, rate ratio, number needed to treat, and incremental cost effectiveness ratio were calculated. The quality of evidence was categorised according to the evidence hierarchy. The strength of recommendation was assessed using the traditional A-D grading scale and a visual analogue scale. RESULTS: Ten key treatment propositions were generated through three Delphi rounds. They included 21 interventions, such as paracetamol, NSAIDs, symptomatic slow acting disease modifying drugs, opioids, intra-articular steroids, non-pharmacological treatment, total hip replacement, osteotomy, and two general propositions. 461 studies were identified from the literature search for the proposed interventions of efficacy, side effects, and cost effectiveness. Research evidence supported 15 interventions in the treatment of hip OA. Evidence specific for the hip was strikingly lacking. Strength of recommendation varied according to category of research evidence and expert opinion. CONCLUSION: Ten key recommendations for the treatment of hip OA were developed based on research evidence and expert consensus. The effectiveness and cost effectiveness of these recommendations were evaluated and the strength of recommendation was scored.

Acetaminophen↗

Expression of VEGF isoforms by epiphyseal chondrocytes during low-oxygen tension is HIF-1 alpha dependent.

OBJECTIVE: To establish the role of hypoxia and HIF-1 alpha for VEGF expression of murine epiphyseal chondrocytes. To analyze the effect of hypoxia on VEGF isoform expression. MATERIALS AND METHODS: VEGF mRNA and VEGF isoform expression was investigated in epiphyses of murine newborns by in situ hybridization and real-time PCR. Further, epiphyseal chondrocytes were isolated from newborn mice with homozygous flanking of the HIF-1 alpha gene with lox-P sites. HIF-1 alpha was deleted by infection with adenovirus containing cre-recombinase. After chondrocytes reached confluency they were exposed to 0.5% or 20% oxygen, respectively. Total VEGF and VEGF isoform mRNA expression levels were measured by real-time PCR. Secreted VEGF protein was determined by ELISA. RESULTS: VEGF mRNA signals were detected in the hypertrophic zone and in the center of the proliferative zone of the murine epiphysis, which is considered to be hypoxic. Real-time PCR revealed that VEGF(120)is the dominant isoform in vivo. In cultured epiphyseal chondrocytes strongly increased VEGF gene expression levels were detected after exposure to hypoxia. Furthermore, secretion of VEGF protein was significantly enhanced under 0.5% oxygen. Remarkably, functional inactivation of HIF-1 alpha abolished the hypoxic increase of VEGF expression in chondrocytes completely. Furthermore, the soluble isoforms VEGF(120)and VEGF(164)are the most abundantly expressed splice variants in chondrocytes exposed to low oxygen levels. CONCLUSIONS: The data presented here clearly indicate that hypoxia is able to induce the synthesis of soluble VEGF isoforms by epiphyseal chondrocytes, most likely through stabilization of HIF-1 alpha. Thus it can be speculated that HIF-1 alpha is an essential prerequisite for hypoxic VEGF synthesis in the epiphysis, thereby contributing to the formation and invasion of blood vessels in long bone development.

Animals↗

Tenascin and aggrecan expression by articular chondrocytes is influenced by interleukin 1beta: a possible explanation for the changes in matrix synthesis during osteoarthritis.

OBJECTIVE: To analyse the distribution patterns of tenascin and proteoglycans in normal and osteoarthritic cartilage, and to determine the effect of interleukin 1beta (IL1beta) on aggrecan and tenascin expression by human articular chondrocytes in vitro. METHODS: Normal and osteoarthritic cartilage and bone samples were obtained during total knee replacements or necropsies. After fixation and decalcification, paraffin embedded specimens were sectioned perpendicular to the surface. Specimens were graded according to Mankin and subdivided into those with normal, and mild, moderate, and severe osteoarthritic lesions. Serial sections were immunostained for tenascin. Tenascin expression by healthy and osteoarthritic chondrocytes was quantified by real time polymerase chain reaction (PCR). Furthermore, in cell culture experiments, human articular chondrocytes were treated with 0.1 or 10 ng/ml IL1beta. Real time PCR analyses of aggrecan and tenascin transcripts (normalised 18S rRNA) were conducted to determine the effect of IL1beta on later mRNA levels. RESULTS: Tenascin was immunodetected in normal and osteoarthritic cartilage. In osteoarthritic cartilage increased tenascin staining was found. Tenascin was found specifically in upper OA cartilage showing a strong reduction of proteoglycans. Greatly increased tenascin transcript levels were detected in osteoarthritic cartilage compared with healthy articular cartilage. IL1beta treatment of articular chondrocytes in vitro significantly increased tenascin transcripts (approximately 200% of control) and strongly reduced aggrecan mRNA levels (approximately 42% of control). CONCLUSIONS: During progression of osteoarthritis the switch in matrix synthesis occurs mainly in upper osteoarthritic cartilage. Furthermore, changes in synthesis patterns of osteoarthritic chondrocytes may be significantly influenced by IL1beta, probably diffusing from the joint cavity within the upper osteoarthritic cartilage.

Aggrecans↗

EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT).

OBJECTIVES: To update the EULAR recommendations for management of knee osteoarthritis (OA) by an evidence based medicine and expert opinion approach. METHODS: The literature search and guidelines were restricted to treatments for knee OA pertaining to clinical and/or radiological OA of any compartment of the knee. Papers for combined treatment of knee and other types of OA were excluded. Medline and Embase were searched using a combination of subject headings and key words. Searches for those treatments previously investigated were conducted for January 1999 to February 2002 and for those treatments not previously investigated for 1966 to February 2002. The level of evidence found for each treatment was documented. Quality scores were determined for each paper, an effect size comparing the treatment with placebo was calculated, where possible, and a toxicity profile was determined for each treatment modality. RESULTS: 497 new publications were identified by the search. Of these, 103 were intervention trials and included in the overall analysis, and 33 treatment modalities were identified. Previously identified publications which were not exclusively knee OA in the initial analysis were rejected. In total, 545 publications were included. Based on the results of the literature search and expert opinion, 10 recommendations for the treatment of knee OA were devised using a five stage Delphi technique. Based on expert opinion, a further set of 10 items was identified by a five stage Delphi technique as important for future research. CONCLUSION: The updated recommendations support some of the previous propositions published in 2000 but also include modified statements and new propositions. Although a large number of treatment options for knee OA exist, the evidence based format of the EULAR Recommendations continues to identify key clinical questions that currently are unanswered.

Adrenal Cortex Hormones↗

[Bone scintigraphy and clinical outcome in rheumatoid gonarthritis].

AIM: For evaluation of the effect of radiosynoviorthesis (RSO) on the early and delayed uptake of (99m)Tc-biphosphonates and its relation to clinical outcome we studied these variables before and after radiosynoviorthesis performed on 41 knees affected by rheumatoid arthritis. METHOD: Thirty-seven patients with rheumatoid gonarthritis were treated by intraarticular injection with 185 MBq yttrium-90 citrate. In four of them both knees were treated so that 41 therapies were evaluated. On the average 35 days before and 120 days after radiosynoviorthesis, the early and delayed uptake of (99m)Tc-diphosphonate (DPD) was measured with a planar gamma camera. Early and late DPD uptake was quantified as a ratio between count values derived from rectangular ROIs placed on the knee treated and on the ipsilateral thigh. The severity of clinical symptoms was assessed on two 3-point rating scales averaged. RESULTS: 30 of the 41 cases favorably responded to radiosynoviorthesis. There was a significant correlation between clinical outcome and pretherapeutic early DPD uptake (EDU) (p<0.05), but not between outcome and pretherapeutic late DPD uptake (DDU). In the whole group, EDU decreased in approximately 76% of cases after therapy (p<0.05), DDU in 54% (p>0.05). In 25 of the 30 responders EDU decreased; EDU increased or remained constant in five of the eleven non-responders. The correlation between outcome and the difference in EDU was significant (r = 0.344; p<0.05). There was no such significant relationship between the difference between pre- and posttherapeutic DDU and clinical course. CONCLUSION: Three-phase bone scintigraphy may contribute to predict and assess the success of radiosynovior-thesis in rheumatoid arthritis of the knee joint.

Adult↗

Matrilin-3 in human articular cartilage: increased expression in osteoarthritis.

OBJECTIVE: Matrilin-3 is a member of the recently described matrilin family of extracellular matrix proteins containing von Willebrand factor A-like domains. The matrilin-3 subunit can form homo-tetramers as well as hetero-oligomers together with subunits of matrilin-1 (cartilage matrix protein). It has a restricted tissue distribution and is strongly expressed in growing skeletal tissues. Detailed information on expression and distribution of extracellular matrix proteins is important to understand cartilage function in health and in disease like osteoarthritis (OA). METHODS: Normal and osteoarthritic cartilage were systematically analysed for matrilin-3 expression, using immunohistochemistry, Western blot analysis, in situ hybridization, and quantitative PCR. RESULTS: Our results indicate that matrilin-3 is a mandatory component of mature articular cartilage with its expression being restricted to chondrocytes from the tangential zone and the upper middle cartilage zone. Osteoarthritic cartilage samples with only moderate morphological osteoarthritic degenerations have elevated levels of matrilin-3 mRNA. In parallel, we found an increased deposition of matrilin-3 protein in the cartilage matrix. Matrilin-3 staining was diffusely distributed in the cartilage matrix, with no cellular staining being detectable. In cartilage samples with minor osteoarthritic lesions, matrilin-3 deposition was restricted to the middle zone and to the upper deep zone. A strong correlation was found between enhanced matrilin-3 gene and protein expression and the extent of tissue damage. Sections with severe osteoarthritic degeneration showed the highest amount of matrilin-3 mRNA, strong signals in in situ hybridization, and prominent protein deposition in the middle and deep cartilage zone. CONCLUSION: We conclude that matrilin-3 is an integral component of human articular cartilage matrix and that the enhanced expression of matrilin-3 in OA may be a cellular response to the modified microenvironment in the disease.

Adult↗

Type IIA procollagen: expression in developing chicken limb cartilage and human osteoarthritic articular cartilage.

Type IIA procollagen is an alternatively spliced product of the type II collagen gene and uniquely contains the cysteine (cys)-rich globular domain in its amino (N)-propeptide. To understand the function of type IIA procollagen in cartilage development under normal and pathologic conditions, the detailed expression pattern of type IIA procollagen was determined in progressive stages of development in embryonic chicken limb cartilages (days 5-19) and in human adult articular cartilage. Utilizing the antibodies specific for the cys-rich domain of the type IIA procollagen N-propeptide, we localized type IIA procollagen in the pericellular and interterritorial matrix of condensing pre-chondrogenic mesenchyme (day 5) and early cartilage (days 7-9). The intensity of immunostaining was gradually lost with cartilage development, and staining became restricted to the inner layer of perichondrium and the articular cap (day 12). Later in development, type IIA procollagen was re-expressed at the onset of cartilage hypertrophy (day 19). Different from type X collagen, which is expressed throughout hypertrophic cartilage, type IIA procollagen expression was transient and restricted to the zone of early hypertrophy. Immunoelectron microscopic and immunoblot analyses showed that a significant amount of the type IIA procollagen N-propeptide, but not the carboxyl (C)-propeptide, was retained in matrix collagen fibrils of embryonic limb cartilage. This suggests that the type IIA procollagen N-propeptide plays previously unrecognized roles in fibrillogenesis and chondrogenesis. We did not detect type IIA procollagen in healthy human adult articular cartilage. Expression of type IIA procollagen, together with that of type X collagen, was activated by articular chondrocytes in the upper zone of moderately and severely affected human osteoarthritic cartilage, suggesting that articular chondrocytes, which normally maintain a stable phenotype, undergo hypertrophic changes in osteoarthritic cartilage. Based on our data, we propose that type IIA procollagen plays a significant role in chondrocyte differentiation and hypertrophy during normal cartilage development as well as in the pathogenesis of osteoarthritis.

Aged↗

[Molecular principles of induction and progression of arthrosis].

From a morphological point of view, osteoarthritis is characterized by continuous loss of the cartilage matrix, an increased density of the subchondral bone, and partial involvement of the synovial compartment. Research activities are focussing on gene expression and gene regulation in normal and osteoarthritic cartilage to develop prognostic markers and new therapeutic strategies. In general, chondrocytes from normal adult articular cartilage show low metabolic activity. However in osteoarthritis, activation and differentiation of chondrocytes occur. Activation involves anabolic pathways such as an enhanced expression of type II collagen as well as catabolic patterns such as the increased expression of matrix metalloproteinases. These metabolic pathways are unbalanced, leading to insufficient cartilage architecture, unable to meet the requirements for mechanical stability and load compensation. In osteoarthritis, chondrocyte differentiation is characterized by the expression of type X collagen. Further differentiation stages have been observed as shown for the expression of osteocalcin, osteopontin, or alkaline phosphatase in articular cartilage. This altered expression pattern of chondrocytes is likely to influence the biochemical and biomechanical properties of the cartilage matrix. In conclusion, new analytic and comparative methods to analyze gene and protein expression offer powerful tools to elucidate candidate genes in osteoarthritis. Detailed information on the regulatory pathways will be the basis for modulation of chondrocyte behavior and, therefore, may lead to new therapeutic approaches in the treatment of osteoarthritis.

Alkaline Phosphatase↗

[Epidemiological arthrosis research].

Osteoarthritis is the most common joint disease worldwide. Epidemiological studies on the prevalence and incidence have documented the role of osteoarthritis in industrial populations. More extensive clinical studies not only focussed on the impact of osteoarthritis on the quality of life, but have also helped to classify this heterogeneous disease and define clinical subsets. Although the methods of epidemiological osteoarthritis research are not without problems, epidemiology has nevertheless clearly defined risk factors of osteoarthritis and evaluated environmental influences such as sports or occupation. Apart from that, epidemiology has also brought new ideas to basic science research and in particular to molecular research on the genetics of osteoarthritis.

Adult↗

Expression of early and late differentiation markers (proliferating cell nuclear antigen, syndecan-3, annexin VI, and alkaline phosphatase) by human osteoarthritic chondrocytes.

Although osteoarthritis is characterized by a progressive loss of the extracellular cartilage matrix, very little is known about the fate of articular chondrocytes during the progression of the disease. In this study we examined the expression of syndecan-3, a marker of early chondrocyte differentiation, and annexin VI, a marker of late chondrocyte differentiation, in mammalian embryonic growth plate cartilage and normal and osteoarthritic human articular cartilage. Whereas syndecan-3 was expressed in the proliferative and hypertrophic zones of growth platecartilage, immunostaining for annexin VI waspredominately found in the hypertrophic and mineralizing zones of fetal bovine growth plate cartilage. Approximately 20% of chondrocytes were immunopositive for syndecan-3 in normal human articular cartilage, the number of syndecan-3-expressing chondrocytes significantly increased during the progression of osteoarthritis with more than 80% syndecan-3-positive cells in the upper zone of severely affected osteoarthritic cartilage. Similarly, the number of annexin VI-expressing cells significantly increased in the upper cartilage zones during the progression of osteoarthritis. Furthermore, immunostaining for proliferating cell nuclear antigen, a marker for cell proliferation, was detected in chondrocytes in the upper zone of osteoarthritic cartilage. Double-labeling experiments with antibodies against syndecan-3 and annexin VI revealed chondrocytes that expressed only syndecan-3, and cells that expressed both syndecan-3 and annexin VI. These results suggest that the expression of early (proliferating cell nuclear antigen, syndecan-3) and late differentiation markers (annexin VI, alkaline phosphatase) is activated in chondrocytes of osteoarthritic cartilage.

Alkaline Phosphatase↗

Vascular endothelial growth factor in articular cartilage of healthy and osteoarthritic human knee joints.

OBJECTIVE: To determine the levels of vascular endothelial growth factor (VEGF) mRNA and protein expression in normal and osteoarthritic (OA) human articular cartilage, and whether VEGF expression alters during the progression of OA. METHODS: Sections from normal and OA human knee cartilage were immunotained with a polyclonal antibody recognising VEGF. In addition, total RNA was isolated from normal and osteoarthritic human knee cartilage and analysed by reverse transcriptase-polymerase chain reaction (RT-PCR) for VEGF mRNA expression. RESULTS: VEGF was found to be present in normal and OA human knee cartilage in all cartilage layers. A significant increase of VEGF immunopositive chondrocytes to up to approximately 82% was detected in severe OA cartilage compared with normal articular cartilage (approximately 56% of immunopositive chondrocytes). RT-PCR analysis showed the expression of VEGF also on the mRNA level. CONCLUSIONS: VEGF is expressed by articular chondrocytes in normal and OA human knee cartilage. The percentage of VEGF immunopositive chondrocytes significantly increases in late stages of the disease. The VEGF transcript levels encoding all four isoforms shows a big variability in samples from different donors, suggesting a distinct regulation of the expression of the four VEGF isoforms in normal and OA cartilage.

Cartilage, Articular↗