Axel Hempfing
University of Bern
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Axel Hempfing.
Arthritis & Rheumatism | 2009
Heiner Appel; G. Ruiz-Heiland; Joachim Listing; Jochen Zwerina; Martin Herrmann; Ruediger B. Mueller; Hildrun Haibel; Xenofon Baraliakos; Axel Hempfing; Martin Rudwaleit; Joachim Sieper; Georg Schett
OBJECTIVE Osteocytes are considered to be sensors of bone damage and regulators of bone mass by specifically expressing sclerostin, an inhibitor of bone formation. The contribution of osteocytes in regulating local bone remodeling in arthritis is unknown. The aim of this study was to investigate the role of osteocytes as contributors to bone remodeling in ankylosing spondylitis (AS). METHODS Sclerostin expression and osteocyte death were assessed by immunohistochemistry in joints derived from patients with AS, patients with rheumatoid arthritis (RA), and patients with osteoarthritis (OA), as well as from control subjects. In addition, the serum level of sclerostin was assessed by enzyme-linked immunosorbent assay in healthy subjects and patients with AS; this assessment included the longitudinal correlation of sclerostin serum levels and radiographic progression in the spine of patients with AS. RESULTS Sclerostin expression was confined exclusively to osteocytes. Whereas the majority of osteocytes in healthy individuals and patients with RA were sclerostin positive, expression was significantly reduced in patients with OA and was virtually absent in patients with AS. Moreover, serum levels of sclerostin were significantly lower in patients with AS than in healthy individuals. Importantly, low serum sclerostin levels in patients with AS were significantly associated with the formation of new syndesmophytes (P = 0.007). CONCLUSION Sclerostin expression is impaired in patients with AS, suggesting a specific alteration of osteocyte function in this disease. A low serum level of sclerostin in the setting of AS is linked to increased structural damage, emphasizing the role of sclerostin in the suppression of bone formation.
Arthritis Research & Therapy | 2011
Heiner Appel; R. Maier; Peihua Wu; Rebecca Scheer; Axel Hempfing; Ralph Kayser; Andreas Thiel; Andreas Radbruch; Christoph Loddenkemper; Joachim Sieper
IntroductionIn this study, we analysed the number of IL-17+ cells in facet joints, in the peripheral blood (PB) and synovial fluid (SF) of spondyloarthritis (SpA) patients and compared these results with those of patients with other rheumatic diseases and controls.MethodsImmunohistochemical analysis of IL-17+ cells was performed in facet joints of 33 ankylosing spondylitis (AS) patients and compared with data from 20 osteoarthritis (OA) patients. The frequency of IL-17+CD4+ T cells in PB and SF of SpA patients (PB n = 30, SF n = 11), rheumatoid arthritis (RA) patients (PB n = 14, SF n = 7), OA patients (PB n = 10) and healthy controls (PB n = 12) was analysed after stimulation with Staphylococcus aureus Enterotoxin B and phorbol 12-myristate 13-acetate/ionomycin and quantified by flow cytometry.ResultsIn AS facet joints, the frequency of IL-17-secreting cells was significantly higher than in samples obtained from OA patients (P < 0.001), with a slight predominance of IL-17+ cells among the mononuclear cells (61.5% ± 14.9%) compared to cells with polysegmental nuclei. Immunofluorescence microscopy revealed that the majority of IL-17+ cells were myeloperoxidase-positive (35.84 ± 13.06/high-power field (HPF) and CD15+ neutrophils (24.25 ± 10.36/HPF), while CD3+ T cells (0.51 ± 0.49/HPF) and AA-1+ mast cells (2.28 ± 1.96/HPF) were less often IL-17-positive. The frequency of IL-17+CD4+ T cells in the PB and SF of SpA patients did not differ significantly compared to RA patients, OA patients or healthy controls.ConclusionsOur data suggest an important role for IL-17 in the inflammatory processes in AS. However, the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response.
Arthritis Research & Therapy | 2006
Heiner Appel; Christoph Loddenkemper; Zarko Grozdanovic; Harald Ebhardt; Marc Dreimann; Axel Hempfing; Harald Stein; Peter Metz-Stavenhagen; Martin Rudwaleit; Joachim Sieper
Ankylosing spondylitis (AS) is a chronic inflammatory disease which affects primarily the sacroiliac joints and the spine. In patients with active disease, magnetic resonance imaging (MRI) of the spine shows areas of bone marrow edema, the histopathological equivalent of which is unknown. In this study we correlate inflammation in the spine of patients with AS as revealed by histological examination with bone marrow edema as detected by MRI. We have compared the histopathological findings of zygapophyseal joints from 8 patients with AS (age: 30 to 64, disease duration 7 to 33 years) undergoing spinal surgery with findings in MRI. For histopathological analysis, we quantified infiltrates of CD3+, CD4+ and CD8+ T cells as well as CD20+ B cells immunohistochemically. Bone marrow edema was evaluated in hematoxylin and eosin stained sections and quantified as the percentage of the bone marrow area involved. All patients with AS showed interstitial mononuclear cell infiltrates and various degrees of bone marrow edema (range from 10% to 60%) in histopathological analysis. However, in only three of eight patients histopathological inflammation and edema in the zygapophyseal joints correlated with bone marrow edema in zygapophyseal joints of the lumbar spine as detected by MRI. Interestingly, two of these patients showed the highest histological score for bone marrow edema (60%). This first study correlating histopathological changes in the spine of patients with AS with findings in MRI scans suggests that a substantial degree of bone marrow inflammation and edema is necessary to be detected by MRI.
Journal of Bone and Joint Surgery-british Volume | 2002
Hubert Nötzli; Klaus A. Siebenrock; Axel Hempfing; L. E. Ramseier; Reinhold Ganz
We used laser Doppler flowmetry (LDF) with a high energy (20 mW) laser to measure perfusion of the femoral head intraoperatively in 32 hips. The surgical procedure was joint debridement requiring dislocation or subluxation of the hip. The laser probe was placed within the anterosuperior quadrant of the femoral head. Blood flow was monitored in specific positions of the hip before and after dislocation or subluxation. With the femoral head reduced, external rotation, both in extension and flexion, caused a reduction of blood flow. During subluxation or dislocation, it was impaired when the posterosuperior femoral neck was allowed to rest on the posterior acetabular rim. A pulsatile signal returned when the hip was reduced, or was taken out of extreme positions when dislocated. After the final reduction, the signal amplitudes were first slightly lower (12%) compared with the initial value but tended to be restored to the initial levels within 30 minutes. Most of the changes in the signal can be explained by compromise of the extraosseous branches of the medial femoral circumflex artery and are reversible. Our study shows that LDF provides proof for the clinical observation that perfusion of the femoral head is maintained after dislocation if specific surgical precautions are followed.
Journal of Bone and Joint Surgery, American Volume | 2007
Richard Placzek; Wolf Drescher; Georg Deuretzbacher; Axel Hempfing; A Ludwig Meiss
BACKGROUND Radial epicondylitis (tennis elbow) is the most frequent type of myotendinosis. Patients can experience substantial loss of function, especially when this condition becomes chronic. A successful therapy has not yet been established. A preliminary study of injections of botulinum toxin A in patients with chronic epicondylitis has shown promising results. METHODS In the present prospective, controlled, double-blinded clinical trial, 130 patients were examined at sixteen study centers. A single injection of botulinum toxin A into the painful origin of the forearm extensor muscles was performed. Follow-up examinations were performed at two, six, twelve, and eighteen weeks. Clinical findings were documented with use of a new clinical pain score and with a visual analogue scale. A global assessment of the result of treatment was also provided by the patient and the attending doctor. Strength of extension of the third finger and the wrist was evaluated with use of the Brunner method, and grip strength (fist closure strength) was measured with a vigorimeter. RESULTS The group treated with botulinum toxin A was found to have a significant improvement in the clinical findings, compared with those in the placebo group, as early as the second week after injection (p = 0.003). Subjective general assessment also showed improvement in that group, compared with the placebo group, at six weeks (p = 0.001) and at the time of the final examination (at eighteen weeks) (p = 0.001). There was a consistent increase in fist closure strength in both the group treated with botulinum toxin A and the control group, but there was no significant difference between groups. As was expected as a side effect, extension of the third finger was observed to be significantly weakened at two weeks but this complication had completely resolved at eighteen weeks. CONCLUSIONS We concluded that local injection of botulinum toxin A is a beneficial treatment for radial epicondylitis (tennis elbow). The treatment can be performed in an outpatient setting and does not impair the patients ability to work.
Journal of Orthopaedic Research | 2003
Axel Hempfing; Michael Leunig; Hubert Nötzli; Martin Beck; Reinhold Ganz
Background: The blood flow to the acetabular fragment is of some concern in juxtaarticular pelvic osteotomies used for the treatment of hip dysplasia. No direct measurements have determined the effect of the Bernese periacetabular osteotomy (PAO) on acetabular perfusion.
The Journal of Rheumatology | 2010
Heiner Appel; R. Maier; Christoph Loddenkemper; Ralph Kayser; Oliver Meier; Axel Hempfing; Joachim Sieper
Objective. New bone formation of the spine is a typical feature of ankylosing spondylitis (AS). It is unknown whether new bone formation is part of a physiological repair process or a unique pathological entity of the disease. Methods. We analyzed zygapophyseal joints from patients with AS and osteoarthritis (OA) undergoing spinal surgery for rigid hyperkyphosis (AS) or radiculopathy caused by severe OA. In 17 patients with AS, 11 with OA, and 5 controls we performed immunohistochemical analysis of osteoprotegerin (OPG), nuclear factor-κB ligand (RANKL), and osteocalcin (OC) expression in osteoblasts and determined the trabecular thickness in AS and OA patients and controls. Osteoclasts were detected by tartrate-resistant alkaline phosphatase (TRAP) staining. Results. Trabecular thickness was significantly lower in patients with AS compared to OA (p = 0.01). The absolute number of CD56+ osteoblasts (p < 0.001) and OC+ (p = 0.002), OPG+ (p = 0.003), and RANKL+ osteoblasts (p = 0.03) in AS patients was also significantly lower than in OA patients. The percentages of OC+, OPG+, and RANKL+ osteoblasts did not differ between AS and OA (p > 0.05 in all cases). In controls, the percentages of OPG+ (p = 0.013) and OC+ (p = 0.034) but not RANKL+ (p > 0.05) osteoblasts were significantly lower compared to AS patients. The frequency of TRAP+ osteoclasts in AS patients was significantly lower compared to OA (p < 0.001), but higher compared to controls. Conclusion. Immunohistochemical analysis of zygapophyseal joints suggested that osteoblast activity is similar in AS and OA, indicating that new bone formation is possibly a physiological function of repair in both diseases.
Journal of Bone and Joint Surgery, American Volume | 2002
Carsten Wingenfeld; Rainer J. Egli; Axel Hempfing; Reinhold Ganz; Michael Leunig
Background: Although transplantation of cryopreserved bone allografts has become a routine procedure in orthopaedic surgery, biological and immunological impairment remains an unsolved problem that causes clinical failures. Experimental and clinical evidence has indicated that bone grafts that are revascularized early remain viable and contribute to union at the recipient site. Unprotected cryopreservation, used in most bone banks to reduce graft antigenicity, is associated with complete loss of graft viability, potentially contributing to graft failure. The differences in the survival of various cell types during cryopreservation with use of dimethyl sulfoxide, particularly the increased sensitivity of leukocytes to fast freezing, has resulted in a new approach to modulate immunogenicity. On the basis of this concept, it was proposed that a reduction in the immune response and enhanced revascularization of osteochondral allografts could be achieved by rapid cryopreservation with dimethyl sulfoxide. To test this hypothesis, angiogenesis and immune tolerance were quantified in a murine model with use of intravital microscopy.Methods: Fresh osteochondral tissue and osteochondral tissue that had been cryopreserved with and without dimethyl sulfoxide was transplanted into dorsal skinfold chambers as isografts and as allografts in presensitized and nonsensitized recipient mice. To quantify angiogenesis, the onset of hemorrhages in the vicinity of the grafts and the revascularization of the grafts were determined by means of intravital fluorescence microscopy. To determine the recipients intravascular immune response to the grafts, the leukocyte-endothelium interaction was assessed on the twelfth day after transplantation.Results: Nine of nine fresh isografts were revascularized at a mean (and standard deviation) of 57 ± 33 hours, eight of nine isografts that had been cryopreserved with dimethyl sulfoxide were revascularized at 98 ± 50 hours, and zero of nine isografts that had been cryopreserved without dimethyl sulfoxide were revascularized. Seven of seven fresh allografts were revascularized at 53 ± 6 hours, and ten of ten allografts that had been cryopreserved with dimethyl sulfoxide were revascularized at 82 ± 29 hours. However, signs of revascularization faded in four of the seven fresh allografts whereas reperfusion was maintained in the majority (seven) of the ten grafts frozen in the presence of dimethyl sulfoxide. Similar to the findings associated with unprotected frozen isografts, zero of ten unprotected frozen allografts were revascularized. None of the allografts that had been transplanted into presensitized recipients were revascularized, regardless of whether they had been implanted fresh (nine grafts) or had been implanted after protected (eight grafts) or unprotected (nine grafts) freezing. Quantification of the leukocyte-endothelium interaction revealed a reduction in the intravascular immune response to frozen allografts (both protected and unprotected) compared with fresh allografts.Conclusion: Osteochondral allografts that had been pretreated by cryopreservation with dimethyl sulfoxide demonstrated improved angiogenesis induction and enhanced immune tolerance compared with unprotected frozen grafts. A selective reduction in donor passenger leukocytes is the proposed mechanism underlying this phenomenon.Clinical Relevance: In the absence of presensitization, cryopreservation with dimethyl sulfoxide appears to reduce the immune response to allografts and to enhance their revascularization; in the presence of presensitization, alternatives to allograft transplantation should be considered since the allografts will be exposed to a deleterious immune response.
Lasers in Surgery and Medicine | 2008
Rainer J. Egli; Agostino Di Criscio; Axel Hempfing; Ralf Schoeniger; Reinhold Ganz; Willy Hofstetter; Michael Leunig
5‐Aminolevulinic acid based photodynamic therapy (5‐ALA‐PDT) has revealed promising results in the treatment of inflammatory joint diseases due to the sensitivity of inflamed synovial tissue. For 5‐ALA‐PDT to be safe and beneficial for intra‐articular applications, resistance of chondrocytes is essential to prevent cartilage damage. As no data yet exist, the aim of the present study was to assess in vitro the response of the chondrocytes to 5‐ALA‐PDT and to compare with osteoblasts and synovial tissue derived cells.
Spine | 2005
Axel Hempfing; Marc Dreimann; Stefan Krebs; Oliver Meier; Hubert Nötzli; Peter Metz-Stavenhagen
Study Design. During anterior spinal surgery, vertebral perfusion was assessed by laser Doppler flowmetry. Blood flow changes were assessed after unilateral ligation and contralateral compression of the segmental vessels. Objective. To assess the influence of unilateral and bilateral segmental vessel occlusion on vertebral blood flow. Summary of Background Data. During anterior spinal surgery, segmental vessels are frequently being ligated. The reduced blood supply to the vertebrae may impair intervertebral fusion, and the decreased spinal cord perfusion may lead to ischemic myelopathy. To our knowledge, this is the first in vivo study to investigate vertebral blood flow. Methods. There were 10 patients who underwent anterior release for adult idiopathic scoliosis (n = 6), Scheuermann disease (n = 3), and posttraumatic kyphosis (n = 1). A high-power laser Doppler flowmeter was used to assess vertebral blood flow. Measurements were performed in 19 thoracic and 4 lumbar vertebrae (n = 23) after unilateral segmental vessel ligation and additional temporary digital compression of the contralateral vessels. Results. Initial mean blood flow was 49.1 ± 27.6 arbitrary units, and all signals were pulsatile. The blood flow decreased by a mean of 8% after unilateral ligation of the segmental vessels. With additional compression of the contralateral vessels, the signal heights decreased significantly by 54% (mean 18.3 ± 7.8 arbitrary units, P = 0.00003), and a loss of the pulsatile pattern was observed in 75% of the vertebrae. On release of digital compression, the signal height as well as the pulsatility promptly returned. Conclusions. Unilateral ligation of segmental vessels led only to a slight decrease of the vertebral blood flow. Future studies may show whether sparing the segmental vessels during anterior fusion enhances bone graft incorporation, thus decreasing the rate of pseudarthrosis. According to clinical data, the risk of neurologic injury through unilateral ligation is negligible. Bilateral segmental vessel occlusion markedly reduced vertebral bloodflow. Therefore, when treating patients with a higher neurologic risk or in revision cases, the surgeon should always consider sparing the segmental vessels.