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Biomedical subjects

H J Häuselmann

Publications and source records attributed to H J Häuselmann.

At least 19 recordsLinked to original sources
PubMed2006

EULAR evidence based recommendations for the management of hand osteoarthritis: report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

OBJECTIVES: To develop evidence based recommendations for the management of hand osteoarthritis (OA). METHODS: The multidisciplinary guideline development group comprised 16 rheumatologists, one physiatrist, one orthopaedic surgeon, two allied health professionals, and one evidence based medicine expert, representing 15 different European countries. Each participant contributed up to 10 propositions describing key clinical points for management of hand OA. Final recommendations were agreed using a Delphi consensus approach. A systematic search of Medline, Embase, CINAHL, Science Citation Index, AMED, Cochrane Library, HTA, and NICE reports was used to identify the best available research evidence to support each proposition. Where possible, the effect size and number needed to treat were calculated for efficacy. Relative risk or odds ratio was estimated for safety, and incremental cost effectiveness ratio was used for cost effectiveness. The strength of recommendation was provided according to research evidence, clinical expertise, and perceived patient preference. RESULTS: Eleven key propositions involving 17 treatment modalities were generated through three Delphi rounds. Treatment topics included general considerations (for example, clinical features, risk factors, comorbidities), non-pharmacological (for example, education plus exercise, local heat, and splint), pharmacological (for example, paracetamol, NSAIDs, NSAIDs plus gastroprotective agents, COX-2 inhibitors, systemic slow acting disease modifying drugs, intra-articular corticosteroids), and surgery. Of 17 treatment modalities, only six were supported by research evidence (education plus exercise, NSAIDs, COX-2 inhibitors, topical NSAIDs, topical capsaicin, and chondroitin sulphate). Others were supported either by evidence extrapolated from studies of OA affecting other joint sites or by expert opinion. Strength of recommendation varied according to level of evidence, benefits and harms/costs of the treatment, and clinical expertise. CONCLUSION: Eleven key recommendations for treatment of hand OA were developed using a combination of research based evidence and expert consensus. The evidence was evaluated and the strength of recommendation was provided.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

[Implantation of matrix-free cartilage transplants in standardized defects in sheep knee joints].

The goal of the current investigation was to make a comparative analysis of regenerative tissue after autologous de novo cartilage transplantation on the femoral condyles of sheep after a chondral defect. One chondral defect measuring 4 mm in diameter was placed in the center of one medial femoral condyle of each of 48 Suffolk sheep. Twelve defects were left to heal spontaneously, 16 defects were covered with periosteal flaps, and 20 defects were filled with autologous de novo cartilage graft. Macroscopic and microscopic assessments were performed at 26 and at 52 weeks. Regeneration was significantly better (p<0.05) in the transplant group than in the control groups at both 26 weeks and 52 weeks. The differences were most evident in the grade of defect filling, cartilage stability, cell distribution, and matrix assessments. Transplantation of immature, autologous de novo cartilage leads to qualitatively better regeneration both macro- and microscopically than does periosteal flap placement alone. The transplanted, immature cartilage tissue undergoes maturation in vivo. The regenerated tissue has hyaline-like features.

Animals↗
PubMed2003

A comprehensive review of treatments for postmenopausal osteoporosis.

The aim of this review is to assess the efficacy of treatments for postmenopausal osteoporosis in women with low bone mass or with an existing vertebral fracture. We searched the literature for studies (randomized, double-masked, placebo-controlled and prospective) that reported on drugs registered in Europe or North America. We included 41 reports on 12 agents. To assess the consistency among the studies for each drug, we plotted the percent change in bone mineral density (BMD) for the control group against the percent change in BMD for the treated group for lumbar spine and femoral neck. We used methods of cluster analysis to determine consistency among the studies. For each agent we summarized the relative risk for vertebral fracture (patients with new fracture) and for hip fractures. The duration of the studies ranged from 1 to 4.3 years. The proportion of patients who discontinued treatment ranged from 4% to 80%. Most of the studies reported on change in BMD. Twenty-six studies (10 drugs) provided data on new vertebral fractures and 12 (6 drugs) on hip fractures. Apart from fluoride effects on spine BMD, increases in BMD with bisphosphonates were greater than those seen with the remaining treatments. Generally, for each agent the changes in BMD (relative to placebo) were consistent among the studies. The exceptions were calcitriol and calcitonin for changes in BMD of the spine and of the femoral neck. Alendronate, calcitonin, risedronate and raloxifene caused significant reductions in the risk of vertebral fractures. Alendronate, risedronate or the combination of calcium plus vitamin D had a significant effect on the risk of hip fracture. Most therapies are effective in increasing BMD; some decrease the risk of vertebral fracture. For hip fracture, alendronate and risedronate reduce the risk in women with osteoporosis, and calcium and vitamin D reduce the risk in institutionalized patients.

Aged↗
PubMed2003

Comparison of three bone ultrasounds for the discrimination of subjects with and without osteoporotic fractures among 7562 elderly women.

UNLABELLED: Bone ultrasound measures (QUSs) can assess fracture risk in the elderly. We compared three QUSs and their association with nonvertebral fracture history in 7562 Swiss women 70-80 years of age. The association between nonvertebral fracture was higher for heel than phalangeal QUS. INTRODUCTION: Because of the high morbidity and mortality associated with osteoporotic fractures, it is essential to detect subjects at risk for such fractures with screening methods. Because quantitative bone ultrasound (QUS) discriminated subjects with osteoporotic fractures from controls in several cross-sectional studies and predicted fractures in prospective studies, QUS could be more practical than DXA for screening. MATERIAL AND METHODS: This cross-sectional and retrospective multicenter (10 centers) study was performed to compare three QUSs (two heel ultrasounds: Achilles+ [GE-Lunar] and Sahara [Hologic]; the phalanges: ultrasound DBM sonic 1200 [IGEA]) for determining by logistic regression nonvertebral fracture odds ratio (OR) in a sample of 7562 Swiss women, 75.3 +/- 3.1 years of age. The two heel QUSs measured the broadband ultrasound attenuation (BUA) and the speed of sound (SOS). In addition, Achilles+ calculated the stiffness index (SI) and the Sahara calculated the quantitative ultrasound index (QUI) from BUA and SOS. The DBM sonic 1200 measured the amplitude-dependent SOS (AD-SOS). RESULTS: Eighty-six women had a history of a traumatic hip fracture after the age of 50, 1594 had a history of forearm fracture, and 2016 had other nonvertebral fractures. No fracture history was reported by 3866 women. Discrimination for hip fracture was higher than for the other nonvertebral fractures. The two heel QUSs had a significantly higher discrimination power than the QUSs of the phalanges, with standardized ORs, adjusted for age and body mass index, ranging from 2.1 to 2.7 (95% CI = 1.6, 3.5) compared with 1.4 (95% CI = 1.1, 1.7) for the AD-SOS of DBM sonic 1200. CONCLUSION: This study showed a high association between heel QUS and hip fracture history in elderly Swiss women. This could justify integration of QUS among screening strategies for identifying elderly women at risk for osteoporotic fractures.

Age Factors↗
PubMed2002

Molecular aspects of pathogenesis in osteoarthritis: the role of inflammation.

Arthritic diseases cause enormous burdens in terms of pain, crippling, and disability. Osteoarthritis (OA), the most common form of arthritis, is characterized by a slow progressive degeneration of articular cartilage. The exact etiology of OA is not known, but the degradation of cartilage matrix components is generally agreed to be due to an increased synthesis and activation of extracellular proteinases, mainly matrix metalloproteinases. Insufficient synthesis of new matrix macromolecules is also thought to be involved, possibly as a consequence of deficient stimulation by growth factors. Although OA is defined as a noninflammatory arthropathy, proinflammatory cytokines such as interleukin-1 have been implicated as important mediators in the disease. In response to interleukin-1, chondrocytes upregulate the production of nitric oxide and prostaglandin E2, two factors that have been shown to induce a number of the cellular changes associated with OA. The generation of these key signal molecules depends on inducible enzymes and can be suppressed by pharmacological inhibitors.

ADAM Proteins↗
PubMed2002

Quality controls for two heel bone ultrasounds used in the Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk Study.

Because of the important morbidity and mortality associated with osteoporosis, it is essential to detect subjects at risk by screening methods, such as bone quantitative ultrasounds (QUSs). Several studies showed that QUS could predict fractures. None, however, compared prospectively different QUS devices, and few data of quality controls (QCs) have been published. The Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk is a prospective multicenter study that compared three QUSs for the assessment of hip fracture risk in a population of 7609 women age >/=70 yr. Because the inclusion phase lasted 20 mo, and because 10 centers participated in this study, QC became a major issue. We therefore developed a QC procedure to assess the stability and precision of the devices, and for their cross-calibration. Our study focuses on the two heel QUSs. The water bath system (Achilles+) had a higher precision than the dry system (Sahara). The QC results were highly dependent on temperature. QUS stability was acceptable, but Sahara must be calibrated regularly. A sufficient homogeneity among all the Sahara devices could be demonstrated, whereas significant differences were found among the Achilles+ devices. For speed of sound, 52% of the differences among the Achilles+ was explained by the water s temperature. However, for broadband ultrasound attenuation, a maximal difference of 23% persisted after adjustment for temperature. Because such differences could influence measurements in vivo, it is crucial to develop standardized phantoms to be used in prospective multicenter studies.

Calcaneus↗
PubMed2001

Nutripharmaceuticals for osteoarthritis.

What is the level of evidence for current symptomatic agents (SYSADOA) in patients with osteoarthritis? Existing publications which met the inclusion criteria were rated by calculating the effect size of the compounds and applying a quality assessment score of the study methodology. This produced a median effect size for the primary outcome measure, pain, of 1.37 (range 0.37-1.50) for chondroitin-sulphate and 0.57 (range 0.26-1.02) for glucosamine-sulphate in patients with knee osteoarthritis. These effect sizes were strongly diminished when only recent high-quality studies were considered (effect size of pain for chondroitin-sulphate 0.37 and for glucosamine-sulphate 0.26). Effect sizes for functional improvement and overall WOMAC index (pain, stiffness and function) were in the same range for both compounds. So far, and in contrast to recent claims, there is no reliable scientific evidence that these two substances have structure-modifying actions with respect to prohibiting, healing or restoring cartilage lesions. There is only scarce or no scientific evidence for the effects of nutrients in patients with knee, hip or hand osteoarthritis. Several large company-sponsored and independent trials with several of these nutripharmaceuticals are ongoing in Europe and the USA.

Chondroitin Sulfates↗
PubMed1999

[Cartilage oligomeric matrix protein (COMP): the role of a non-collagen cartilage matrix protein as a marker of disease activity and joint destruction in patients with rheumatoid arthritis and osteoarthritis].

UNLABELLED: Today, we can assess criteria to predict the tissue destruction and progression of Rheumatoid Arthritis (RA) and Osteoarthritis (OA) only in a late stage of the disease. It would be an advantage to have biochemical markers of disease activity and joint destruction to optimize therapy. PATIENTS AND METHODS: In this cross-sectional study with 37 RA and 20 OA patients (disease duration 119 +/- 130 months for RA and 41 +/- 73 months for OA), ESR, CRP, disease activity score (DAS), the functional status of RA (American College of Rheumatology), and the radiological scoring systems of Larsen and Kellgren/Lawrence, respectively, were used as parameters for disease activity and joint destruction. Cartilage oligomeric matrix protein (COMP) was measured with an enzyme-linked immunosorbent assay (ELISA) in serum and synovial fluid, COMP fragments with immunoblot in the synovial fluid. RESULTS: The mean COMP value in synovial fluid was 38 ug/ml (RA) and 46 ug/ml (OA); 6.5 ug/ml (RA) and 3.4 ug/ml (OA) in serum. RA patients had a higher amount of small COMP fragments in synovial fluid than OA patients. In RA patients, there was a significant positive correlation between disease activity (DAS) and COMP in synovial fluid and serum, a negative correlation between functional status of RA and serum COMP and between radiologic joint destruction of the knee and serum COMP. In OA patients, there was a significant correlation of joint space width and synovial fluid COMP. DISCUSSION: A high clinical disease activity (DAS) correlated with high COMP values in serum and synovial fluid and with increasing proteolytic activity (higher amount of small COMP fragments especially in RA). An increased turnover of cartilage matrix in joint inflammation might explain this correlation. The correlation of decreased COMP with decreased functional status in RA and increased joint destruction is compatible with a loss of cartilage and less turnover. The correlation between joint space width and increased COMP in OA patients with short disease duration might be explained with a higher turnover of the cartilage matrix in the early stage of the disease.

Adult↗
PubMed1999

Follicle-forming cat thyroid cell lines synthesizing extracellular matrix and basal membrane components: a new tool for the study of thyroidal morphogenesis.

Interactions between follicular epithelial cells and extracellular matrix (ECM) are supposed to play an important role in the development and maintenance of thyroid tissue architecture. In the present study we have therefore investigated the synthesis of ECM components by a feline thyroid cell line which is able to form follicle-like structures in vitro, and also in v-ras-transfected and control-transfected sublines. Transfections were performed by lipofection with pZSR (viral Harvey ras gene; neo) and pSV2-neo (control, neo only) plasmids. We have adapted a semisolid culture system composed exclusively of polymerized alginate and therefore devoid of ECM components. Feline cells embedded in alginate gels as single cells and cultured for up to 90 days formed cell clusters within 10 days. Follicle-like structures were formed in the original cell lines and also in the v-ras- and control-transfected cells. Differences in proliferation rates were observed, the v-ras-transfected cells growing up to two to three times faster than the non-transfected cells. Immunostaining was done using rabbit first antibodies directed against mouse collagen IV, human fibronectin, laminin (tumor Engelbreth-Holm-Swarm laminin), perlecan and other ECM components. For comparison, immunostaining was also performed on cryosections of nodular goiters of six hyperthyroid cats. The cell lines and their transfected clones stained strongly positive for collagen IV and fibronectin, and positively but less strongly for laminin and perlecan. The cat goiter tissue stained positively for collagen IV, laminin, perlecan, and fibronectin, and positive staining for S-laminin (containing the beta2-chain) was seen in blood vessel walls in this tissue. In conclusion, cat cell lines grow three-dimensionally in alginate beads over several weeks, they form follicle-like structures and express the same ECM components as the native cat goiter tissue. Transfection with v-ras does increase proliferation rate, but does not fundamentally alter formation of follicle-like structures and ECM expression. Alginate gel culture is a promising new tool for the study of follicular morphogenesis, polarity, the expression pattern of ECM components and of the interaction between thyrocytes and ECM. It avoids interference caused by gels composed of ECM components.

Alginates↗
PubMed1998

[From chondrocyte culture to joint cartilage replacement. Development of de novo cartilage in vitro].

Local repair of acute or chronic cartilage lesions has not been successful so far. An attempt has been made to use synthetic materials to improve the quality of the repair tissue, but no method has achieved reliable regrowth of normal hyaline cartilage with adequate biomechanical properties and bonding to surrounding tissue. After publication of the first short-term results of chondrocyte transplantation in patients with localized cartilage lesions of the knee joints by a Swedish group in 1994 [1], the situation seems to have changed. Even though the advantages of this method of chondrocyte transplantation is a matter of controversy, the interest in the so-called "Carticel" approach has grown steadily. Indeed, the technique was recently approved by the FDA, on condition of a randomized, "placebo"-controlled trial. In view of this rapid development, we feel that independent experimental studies are urgently needed. In this article we present our own results in synthesizing de novo cartilage from cultured and phenotypically stable chondrocytes in a truly three-dimensional cartilage-like polyanionic matrix. With the experience gained in animals, we expect to set the stage for future experimental therapy in young human patients with early cartilage lesions.

Animals↗
PubMed1998

Differences in nitric oxide production by superficial and deep human articular chondrocytes: implications for proteoglycan turnover in inflammatory joint diseases.

During inflammatory joint diseases, chondrocytes are exposed to cytokines such as IL-1 that induce the synthesis of nitric oxide (NO). Chondrocytes from different zones of the articular cartilage are known to have different metabolic properties. In the present study, we have demonstrated that chondrocytes recovered from the superficial zone of normal, human, articular cartilage synthesize approximately 2 to 3 times as much NO in response to IL-1 as chondrocytes recovered from the deep zone of the same cartilage. Production of NO by normal cartilage in response to IL-1 was also found to decrease with age. Addition of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMA, 1 mM) blocked NO production by cells of both zones. L-NMA completely reversed the suppression of proteoglycan synthesis imposed by IL-1 in deep chondrocytes, but produced only partial reversal in superficial cells. As noted previously, IL-1 failed to elicit a strong catabolic response in cultures of human cartilage. In the presence of L-NMA, however, IL-1 reduced the metabolic t(1/2) of proteoglycans by approximately 50% in both the superficial and deep zones. This suggests that NO has, directly or indirectly, an anticatabolic effect in human cartilage. These data confirm the metabolic heterogeneity of human chondrocytes, and suggest that NO may be involved to different degrees as an endogenous modulator of the turnover of the cartilaginous matrix in different zones of articular cartilage.

Adolescent↗
PubMed1998

Persistent high serum levels of cartilage oligomeric matrix protein in a subgroup of patients with traumatic knee injury.

The objective was to assess whether changes of cartilage oligomeric matrix protein (COMP) serum levels can predict the development of osteoarthritis following traumatic knee injury. Sera and synovial fluids were acquired at surgery (T0) and postoperatively during the first (T1) and second (T2) year from 30 knee-injured patients. COMP levels and anti-COMP autoantibodies were quantified by ELISA. Radiographs and patient questionnaires were used to assess outcomes. At T0, compared with controls (1.6 +/- 1.6 micrograms/ml), the serum COMP concentration was significantly elevated (6.5 +/- 2.8 micrograms/ml) with a tendency to further increase (T0 vs. T1, P = 0.076) and subsequently decrease (T1 vs. T2, P = 0.074). However, individual variations are observed, e.g. persistently high (8/30) or increasing (T0 to T2, 8/30) serum COMP. Ten of these patients have elevated COMP at T2 that increased from T0. COMP levels in serum and synovial fluid correlated significantly (P = 0.012). Interestingly, some patients who revealed increasing serum levels of COMP from T0 to T2 displayed anti-COMP autoantibodies. These data suggest that local immune response could contribute to further joint damage. The subgroup of 10 patients (33%) with elevated and increasing serum COMP levels and in particular the patients with antibodies against cartilage matrix molecules appear at increased risk for developing posttraumatic osteoarthritis.

Adult↗
PubMed1998

Differential effects of IGF-1 and TGF beta-2 on the assembly of proteoglycans in pericellular and territorial matrix by cultured bovine articular chondrocytes.

OBJECTIVES: Knowledge of matrix assembly is necessary to understand the pathogenesis of disease processes and to find solutions for repair of articular cartilage lesions. The influence of growth factors on matrix assembly is largely unknown. We investigated whether, and to what degree, insulin-like growth factor (IGF-1) and transforming growth factor beta-2 (TGF beta-2) influence proteoglycan synthesis and accumulation in the cell-associated matrix compartment (consisting of pericellular and territorial matrix) compared to the further-removed matrix compartment (consisting of the interterritorial matrix). DESIGN: Bovine articular chondrocytes were cultured in alginate beads for day 13. The effect of addition of 25 ng/ml IGF-1 or 25 ng/ml TGF beta-2 during the last 7 days in culture was determined. Cell-associated and further-removed matrix compartments were separated by centrifugation after sodium citrate/EDTA treatment. The amount of DNA, the total amount of proteoglycans and the amount of newly synthesized proteoglycans were analyzed biochemically. Morphometric analysis on electron micrographs was used to calculate the volumes of the cell-associated and further-removed matrix components. RESULTS: It was demonstrated in control beads that 25 +/- 8% of the proteoglycans were laid down in the cell-associated matrix compartment compared with 75 +/- 8% in the further-removed matrix compartment. The cell-associated matrix compartment in intact beads could be recognized in electron microscopy by a delineation of dense amorph material. Morphometric evaluation showed a relative volume of the cell-associated matrix compartment of 5.2 +/- 0.6% compared with 91.3 +/- 0.8% of the further-removed matrix compartment and 3.5 +/- 0.3% of the area occupied by cells. Combination of biochemical and morphometric results showed that the concentration of proteoglycans in the cell-associated matrix compartment was 3.63 +/- 0.32 mg/ml. By adding IGF-1 or TGF beta-2, the amount of both total accumulated proteoglycans and newly synthesized [35S]proteoglycans at day 13 in culture increased. In addition to an overall rise in proteoglycan content, IGF-1 significantly increased (24%) the percentage of proteoglycans laid down in the cell-associated matrix compartment while not changing the relative volume of this compartment (5.2 +/- 0.8%). This leads to a 82% (P < 0.05) increase in the proteoglycan concentration in the cell-associated matrix compartment compared to control beads. In contrast, TGF beta-2 significantly decreased (24%) the relative amount of proteoglycans in the cell-associated matrix compartment which was paralleled by a reduction of the relative volume from 5.2 +/- 0.6 to 3.6 +/- 1.4%. This leads to a significant increase of 87% of the proteoglycan concentration in the cell-associated matrix compartment. CONCLUSIONS: This study demonstrates that both IGF-1 and TGF beta-2 significantly but differently influence proteoglycan synthesis and accumulation in the cell-associated matrix compartment of cultured bovine chondrocytes in alginate. Both growth factors increase the concentration of proteoglycans in the cell-associated matrix compartment. However, addition of TGF beta-2 to bovine articular chondrocytes cultured in alginate beads for 13 days results in a significant reduction of the relative volume of the pericellular matrix compartment compared to controls, indicating differences in assembly of the matrix.

Animals↗
PubMed1998

Analysis of cartilage oligomeric matrix protein (COMP) in synovial fibroblasts and synovial fluids.

We investigated the expression of cartilage oligomeric matrix protein (COMP) in normal and rheumatoid arthritis (RA) synovial fibroblasts. In situ hybridization (ISH) was conducted on synovial specimens from five RA patients applying specific probes for COMP or fibroblast collagen type I. ISH was combined with immunohistochemistry, applying antibodies to the macrophage marker CD68. Ribonuclease protection assay (RPA) and rapid amplification of 3'-cDNA ends (3'-RACE) were performed on total RNA from normal and RA synovial fibroblast cultures. Protein extracts from fibroblasts and culture supernatants were compared with synovial fluids and protein extracts from isolated chondrocytes by Western blot utilizing polyclonal and monoclonal antibodies (18-G3 mAb) to COMP. COMP mRNA was detected in fibroblasts of RA synovium by ISH, and in normal and RA synovial fibroblast cultures by RPA. 3'-RACE demonstrated sequence homology of chondrocyte and synovial fibroblast COMP along the coding sequence. COMP protein was detected in synovial fibroblasts and culture supernatants by immunoblot. Using polyclonal antibodies, the major portion of COMP from fibroblasts and culture supernatants was present as low-molecular-weight (LMW) bands, corresponding to those found in synovial fluids. These LMW COMP bands, however, were not detected in any of the cells or tissues tested using 18-G3 mAb. In protein extracts from chondrocytes and in COMP purified from cartilage, these LMW bands could not be detected. In conclusion, the data suggest that certain forms of COMP detected in synovial fluid are secreted from synovial fibroblasts and could be distinguished by specific mAbs from COMP secreted by chondrocytes.

Arthritis, Rheumatoid↗
PubMed1998

In vivo high resolution 3D-QCT of the human forearm.

In vivo examinations of bone microarchitecture have become available recently through high resolution computed tomography (3D-QCT) and magnetic resonance imaging. The spatial resolution of the resulting images, however, is not sufficient to depict individual trabeculae in their true shape. Nevertheless, structural indices such as relative bone volume, trabecular number, mean thickness and mean separation can be extracted with the help of a ridge detection algorithm. Precision of the procedure is of the order of 1%, accuracy is ascertained using a micro-CT based calibration. In this work we report first results of time serial examinations. Eighteen healthy postmenopausal women (no HRT) were measured at months 0, 6, and 12, and the temporal changes were analyzed. Examination site was the distal radius. The above mentioned structural indices, the average densities and the thickness of the cortical shell were determined. Of the 18 women 6 showed no significant bone loss of any kind, 5 lost primarily cancellous bone, 4 lost primarily cortical bone, and 3 had a substantial loss of cortical as well as cancellous bone. We conclude that even in a homogenous group such as postmenopausal women, there are considerable differences in the reason why bone is weakened and that high resolution 3D-QCT allows to differentiate between various types of bone loss.

Bone Density↗