Minimal-invasive pain procedures are effective in different degenerative pain generators in CLBP: A prospective cohort study.

BACKGROUND: It is estimated that a significant number of spinal surgeries are performed, but many patients do not often benefit. OBJECTIVE: Our aim was to determine how effective minimally invasive pain procedures (MIP) are in chronic low back pain (CLBP) patients with proven degenerative causes (specific low back pain). METHODS: 386 eligible patients with CLBP/sciatica resistant to conservative therapy and scheduled for open surgery were screened, and 167 could be enrolled in this study. Indications for MIP in the remaining 150 individuals were made by one experienced spinal surgeon. Before and 6 months after the intervention, the numeric rating scale (NRS) and Oswestry Disability Index (ODI) were recorded. MIP was performed, such as radiofrequency of the facet and SI-joint, intradiscal electrothermal therapy in case of discogenic pain, as well as epidural neuroplasty in patients with disc herniation/epidural fibrosis. RESULTS: There was a statistically significant decrease in NRS (p< 0.05), as well as a significant increase in ODI (p< 0.001) 6 months after the procedures. This was also true for the results of all different pain generators and subsequent performed procedures alone. CONCLUSIONS: The indication of MIP should be routinely reviewed in patients with CLBP to avoid potentially open surgery and a burden on healthcare costs.

[Risk of Developing Clinical Symptomatically Postmeniscectomy Bone Marrow Edema]. / Risiko des Auftretens eines klinisch symptomatischen Knochenmarködems nach arthroskopischer Meniskusteilresektion.

BACKGROUND: Bone marrow edema (BME) of the knee is often seen in MRI and has several different underlying pathologies. The correlation between disorders of the knee joint and a BME is not fully understood yet. Persistent or progressive postoperative pain and/or functional impairment after arthroscopic partial meniscectomy is still a common phenomenon in many patients. The aim of this prospective clinical trial was to find a correlation between the typical postoperative disorders and BME in MRI and to identify possible therapeutic consequences. PATIENTS, MATERIAL AND METHODS: 150 consecutive patients with preoperatively diagnosed meniscus defects and without any previous operation and no BME underwent arthroscopic partial meniscectomy. A two- to three-day resting period was established postoperatively. The patients then rapidly returned to full weight bearing. No crutches were used. As a standard analgetic, we used diclofenac 50 mg three times a day for three days. Clinical control and removal of the sutures was performed on day 8 postoperatively. The patients' pain status was controlled by using the IKDC score and the Visual Analogue Scale (VAS) before and six weeks after surgery. Six weeks after the surgical intervention, the patients underwent a standardized physical examination and, if there was ongoing functional impairment or discomfort of the knee, a new MRI was performed. However, if patients showed signs or severe discomfort prior to the end of the six-week observation period an MRI was scheduled earlier. RESULTS: Postoperatively 11 of the 150 patients (7,3 %) developed progressive discomfort with pain during stress and also by night. A postoperative BME in the MRI was seen in all 11 symptomatic patients (100 %). We saw a significant correlation to women older than 70 years (p < 0.05). The VAS score six weeks after arthroscopy was significant reduced in the group without any clinical symptoms (2.63 ± 2.83 after arthroscopy and 4.27 ± 2.36 MW ± SEM before arthroscopy) compared to the group with proven BME (5.09 ± 2.74 before arthroscopy and 5.27 ± 2.57 MW ± SEM after arthroscopy; p < 0.05). The IKDC score was significantly enhanced in the clinical asymptomatic group: 58.1 ± 10.53 in comparison to the patients with proven BME, with 35.32 ± 13.2 MW ± SEM (p < 0.05). CONCLUSION: Patients with clinical symptomatic BME showed a significantly higher VAS score and a significantly lower IKDC score postoperatively. Therefore, in patients with postoperative discomfort, a prompt MRI should be performed and, if a BME is proven, further therapy should be modified.

Timing of cervical spine stabilisation and outcome in patients with rheumatoid arthritis.

One complication of rheumatoid arthritis (RA) is the involvement of the cervical spine (CS). Although prophylactic stabilisation is recommended, the timing at which this should occur is poorly defined. The aim of our study was to evaluate the course of neurological symptoms in terms of the timing of surgery. A total of 34 patients with RA and CS involvement were surgically stabilised. These patients were classified using the Ranawat (RW) score both preoperatively and at an average of 54 months post-operatively. For each patient, the presence of atlantoaxial and subaxial subluxation as well as vertical migration of the odontoid was recorded. The anterior atlantodental interval was also assessed pre- and post-operatively. Improvement was obtained in 20 patients, the clinical situation remained unchanged in three patients and three patients manifested disease progression. In terms of the RW score, the 16 patients with pre-operative RW grades I-II showed no deterioration at the post-operative follow-up, with 13 of these patients showing an improvement; the 12 patients with pre-operative RW grades IIIA-IIIB did not show any improvement of neurological symptoms at follow-up, although seven of these patients subjectively assessed the symptoms to be less severe after surgery; three other patients showed a worsening of symptoms. Our results suggest that preventive stabilisation of CS in RA leads to acceptable results, although the complications of the surgery are obvious. However, early operative treatment may delay the detrimental course of cervical myelopathy in RA.

Selective inhibition of platelets by the GPIIb/IIIa receptor antagonist Tirofiban reduces leukocyte-endothelial cell interaction in murine antigen-induced arthritis.

OBJECTIVE: Inflammation is associated with the invasion of leukocytes into affected tissues and with the up-regulation of platelet activation and adhesion. Assuming that leukocyte accumulation is linked to platelet aggregation, the aim of our study was to examine the effects of selective platelet inhibition by the glycoprotein (GP) IIb/IIIa receptor antagonist Tirofiban on the leukocyte-endothelial cell interaction. MATERIAL AND METHODS: We used the model of antigen-induced arthritis (AiA) to induce inflammatory changes in the synovial microcirculation. Ex vivo labelled platelets and in vivo fluorescence-labelled leukocytes were visualized by intravital microscopy (IVM). C57/Bl6 mice were allocated to four groups; two control groups with saline or Tirofiban and two groups with AiA that also received either saline or Tirofiban (0.5 microg/g BW) intravenously. RESULTS: There was no significant change in platelet- or leukocyte- endothelial cell interaction in the endothelium in healthy control animals. In contrast, after selective inhibition of platelets, the platelet- and leukocyte-endothelial cell interaction was significantly reduced in arthritic mice and reached the level of the healthy control groups. CONCLUSION: Selective platelet inhibition by Tirofiban resulted in reduced leukocyte-endothelial cell interactions in AiA. Consequently, platelets contribute to leukocyte adhesion in AiA via GPIIb/IIIa and therefore platelet inhibition could become an additional therapy option in chronic arthritic disease.

In vivo interactions of platelets and leucocytes with the endothelium in murine antigen-induced arthritis: the role of P-selectin.

OBJECTIVE: Platelets are thought to participate in the pathogenesis of chronic inflammatory diseases such as rheumatoid arthritis (RA). We showed recently an in vivo increase in platelet-endothelial cell interactions in mice with antigen-induced arthritis (AiA). The underlying mechanisms are not yet clear. The aim of this study was to investigate the impact of P-selectin in AiA by means of intravital fluorescence microscopy (IVM). METHODS: C57/Bl6 mice and P-selectin-deficient mice were divided into four groups (n = 7; control/AiA per strain). The extent of AiA was assessed by measuring knee joint swelling and by histological scoring. Rolling and adherent fluorescence-labelled platelets and leucocytes were investigated by IVM. RESULTS: In arthritic P-selectin-deficient mice (rolling: 0.05+/-0.01; adherent: 130+/-20 mm(-2)), compared to arthritic C57/Bl6 mice (rolling: 0.20+/-0.04; adherent: 1910+/-200 mm(-2)), platelet interaction was significantly reduced (p<0.05) and reached the level of both control groups without AiA. In addition, interaction of leucocytes in P-selectin-deficient arthritic animals (rolling: 0.12+/-0.06; adherent: 387+/-37 mm(-2)) was significantly decreased in comparison to arthritic C57/Bl6 animals (rolling: 0.21+/-0.06; adherent: 1492+/-284 mm(-2); p<0.05). Swelling of the knee joint and histological scoring were reduced in arthritic P-selectin-deficient mice compared to arthritic C57/Bl6 mice. CONCLUSION: We have demonstrated for the first time in vivo a significant decrease in the interaction of platelets and leucocytes with the endothelium in P-selectin-deficient mice with AiA and a reduction in clinical and histological symptoms of arthritis. These findings suggest that leucocyte-endothelial cell interactions depend at least partially on platelet P-selectin and therefore platelets may be responsible for the leucocyte tissue damage in AiA.

Platelet P-selectin is significantly involved in leukocyte-endothelial cell interaction in murine antigen-induced arthritis.

There is growing evidence that platelets play an important role in the development and maintenance of rheumatoid arthritis. Activation and adherence of platelets in the synovial microcirculation might be in part responsible for endothelial damage and activation of leukocytes. Recent findings show a direct influence of P-selectin on platelet- and leukocyte-endothelial cell interaction in mice with Antigen-induced Arthritis (AiA). P-selectin is only expressed by platelets and endothelial cells, not by leukocytes. Therefore, the aim of the present study was to investigate the differential influence of platelet and endothelial P-selectin on the extent of inflammation in AiA. AiA was induced in wild-type mice and in P-selectin-deficient mice from the same genetic background (four groups: each n = 7). Intravital fluorescence microscopy (IVM) was used to visualize platelets and leukocytes in the synovial microcirculation at day 8 after AiA. Platelets from either strain were fluorescence-labelled ex vivo and transferred into either strain. We were able to demonstrate a significant decrease of platelet- and leukocyte-endothelial cell interaction in P-selectin-deficient mice with AiA in comparison to wild-type mice with AiA. When wild-type platelets were donated into P-selectin-deficient AiA recipients, the leukocyte-endothelial cell interaction was significantly increased compared to the group consisting of P-selectin-deficient recipient and donor mice. These are the first in vivo results showing that the P-selectin stored in platelets is at least partly responsible for the leukocyte-endothelial cell interaction and the resulting tissue damage in AiA. In the future, a suppression of platelet P-selectin could potentially become a treatment option for reducing the effects of rheumatoid arthritis.

Endothelial iNOS versus platelet iNOS: responsibility for the platelet/leukocyte endothelial cell interaction in murine antigen induced arthritis in vivo.

OBJECTIVE: Since an increase of platelet-endothelial cell interactions has been observed in mice with Antigen- induced-Arthritis (AiA) as well as an increase of NO expression, the aim of our study was to investigate in vivo the influence of NO, especially the platelet and endothelial inducible NO Synthase, on the platelet- and leukocyte endothelial cell interaction. MATERIAL AND METHODS: C57/Bl6 mice and iNOS deficient mice were disposed in 6 groups (each=7). After induction of AiA, rolling and adherent fluorescence labelled platelets and leukocytes were investigated by intravital microscopy (IVM) on day 8 after AiA. Rank SUM Test and ANOVA on ranks have been performed regarding the data. RESULTS: All arthritic mice presented an increase in platelet and leukocyte interaction with the endothelium compared to control groups. The arthritic iNOS deficient mice showed a more intense interaction of platelets and leukocytes with the endothelium in comparison with the wild-type arthritic mice. The group using arthritic wild-type recipient and iNOS deficient donor mice showed an increase in cell-interactions, leading to an endothelial effect, compared to the group using iNOS deficient arthritic recipient and wild-type donor mice. CONCLUSION: The IVM data lead to an anti-inflammatory effect of NO, since NO followed an increase in platelet- and leukocyte- endothelial cell interaction in iNOS deficient mice with AiA. In addition, we have shown for the first time in vivo that platelet NO produced by iNOS seems to have a minor influence on the leukocyte induced tissue damage in contrast to endothelial iNOS. Therefore, selective platelet inhibition would not interfere with the protective effect of NO.

Percutaneous cryodenervation of lumbar facet joints: a prospective clinical trial.

Facet joint pain is an important aspect of degenerative lumbar spine disease, and radiofrequency medial branch neurotomy remains an established therapy, while cryodenervation has still been poorly examined. This study was undertaken to examine the effects of medial branch cryodenervation in the treatment of lumbar facet joint pain. This was a prospective clinical case series. Patient selection was based on the history, physical examination and positive medial branch blocks. Percutaneous medial branch cryodenervation was performed using a Lloyd Neurostat 2000. Target parameters were low back pain (VAS), limitation of activity (McNab) and overall satisfaction. Fifty patients were recruited, and 46 completed the study. The follow-up time was 1 year. At 6 weeks, 33 patients (72%) were pain free or had major improvement of low back pain; 13 (28%) had no or little improvement. Including failures, mean low back pain decreased significantly from 7.7 preoperatively to 3.2 at 6 weeks, 3.3 at 3 months, 3.0 at 6 months and 4.2 at 12 months (P<0.0001). Limitation of the activities of daily living improved parallel to reduced pain. Our results suggest that medial branch cryodenervation is a safe and effective treatment for lumbar facet joint pain.

Platelet-endothelial cell interactions in murine antigen-induced arthritis.

OBJECTIVES: Growing evidence supports the substantial pathophysiological impact of platelets on the development of rheumatoid arthritis. At present there are no methods for studying these cellular mechanisms in vivo. The aim of this study was to visualize and investigate platelet-endothelial cell interaction in the knee joint of mice with antigen-induced arthritis (AiA) by means of intravital microscopy. METHODS: In 14 mice (Balbc) intravital microscopic assessment was performed on day 8 after AiA induction in two groups (controls, AiA). The severity of AiA was assessed by measuring knee joint swelling and by histological scoring. Ex vivo fluorescently labelled rolling and adherent platelets and leucocyte-endothelium interactions were investigated by intravital fluorescence microscopy. RESULTS: Swelling of the knee joint as well as histological score was significantly enhanced in arthritic animals compared with controls. In control mice intravital microscopy revealed low baseline rolling and sticking of leucocytes and fluorescently labelled platelets. AiA induced a significant increase in the fraction of rolling leucocytes (3 times) and rolling platelets (6 times) compared to the control group. Furthermore, AiA induction resulted in a significantly enhanced number of adherent leucocytes (3-fold) and adherent platelets (12-fold) in comparison with control animals. CONCLUSIONS: Platelet kinetics were directly analysed using intravital microscopy in the arthritic microcirculation in vivo for the first time. We provide the first evidence that platelets accumulate in arthritic vessels, indicating platelet activation due to AiA. Platelet recruitment and subsequent activation might play an important role in the pathogenesis of rheumatoid arthritis.

Particles of all sizes provoke inflammatory responses in vivo.

The aim of this study was to investigate whether all sizes of wear particles are capable of provoking inflammatory responses and whether there are different responses among different particle sizes. The knees of 40 female Balb/c mice were injected with polystyrene particles of three different diameters, 0.5 microm, 2.0 microm, and 75 microm, using a 0.1% vol/vol concentration. Seven days after particle injection, assessment of the synovial microcirculation using intravital microscopy, and histologic examination, were done. All the mice injected with polystyrene particles had enhanced leukocyte-endothelial cell interactions and histologic scores regardless of particle size when compared with control animals injected with sterile phosphate buffered saline. Polystyrene particles 0.5 microm in size provoked stronger membrane thickening and increased leukocyte-endothelial cell interactions than 75-microm particles. The fraction of rolling leukocytes was enhanced in the 2.0-microm particle group when compared with the 75-microm particle group. These results indicate that polystyrene particles of all sizes (0.5 microm, 2.0 microm, and 75 microm) are capable of inducing an inflammatory response. Small particles (0.5 microm, 2.0 microm) seem to provoke a stronger inflammatory response than larger particles (75 microm) in conditions with equal particle volume.

The effects of Celecoxib on inflammation and synovial microcirculation in murine antigen-induced arthritis.

OBJECTIVE: There is controversy about the effects of cyclooxygenase-2 (COX-2) on adhesion molecules and the microvasculature in inflamed tissue. Thus, the aim of this study was to assess COX-2-expression in Antigen-induced Arthritis (AiA) and to investigate the effects of selective COX-2 inhibition by Celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide) (CXB), on synovial microcirculation and adhesion molecule expression in arthritic as well as healthy mice. METHODS: Balb/c mice were allocated to 4 groups; 2 control groups with saline or CXB and 2 groups with AiA which also received saline or CXB (30 mg/kg BW in 0.3 ml solution). The severity of arthritis was assessed by changes in the transverse joint diameter On day 14 after AiA-induction, the patella tendon of the left knee joint was microsurgically resected and intravital fluorescence microscopy on synovial tissue was performed. Finally, the knee joint was removed for histology and immunohistochmistry. RESULTS: COX-2-expression in the inflamed synovium was demonstrated by immunohistochemistry. Application of Celecoxib resulted in a significant reduction in the rolling leukocyte fraction as well as in the number of leukocytes adherent to the endothelium (0.25 +/- 0. 1 and 96 +/- 34 cells/mm2 respectively) in comparison to the untreated animals with AiA (0.44 +/- 0.03 and 206 +/- 22 cells/mm2 respectively). Additionally, CXB-treated arthritic animals showed significantly less knee joint swelling and reduced adhesion molecule expression. CONCLUSION: In the present study, COX-2 expression in the synovial tissue of mice with AiA could be demonstrated. Selective COX-2 inhibition with CXB resulted in reduced leucocyte-endothelial cell interactions and decreased adhesion molecule expression. Evidence for a protective role of COX-2 in mouse AiA was not found.

[Chronic radiculopathy. Use of minimally invasive percutaneous epidural neurolysis according to Racz]. / Chronische Radikulopathie. Einsatz der minimal-invasiven perkutanen epiduralen Neurolyse nach Racz.

Treatment of chronic low back pain exhibiting radicular symptoms poses a clinical problem that has not yet been solved. The technique of percutaneous minimally invasive neurolysis described by Racz is being performed increasingly to treat chronic radiculopathy. A total of 61 patients with corresponding symptomatology after screening for inclusion and exclusion criteria in the region of the lumbar spinal nerve were treated with the Racz catheter technique. Distinct clinical improvement was observed at the 3- and 6-month follow-ups after percutaneous minimally invasive epidural neurolysis. Subjective pain perception, quantified by the McNab score, clearly improved after 3 as well as 6 months. With the exception of partial catheter shearing in two cases and one occurrence of infection, no relevant side effects were noted. The Racz catheter technique for treatment of chronic radiculopathy following disk surgery is suitable with minimal side effects.

Tunnel enlargement and changes in synovial fluid cytokine profile following anterior cruciate ligament reconstruction with patellar tendon and hamstring tendon autografts.

There is growing evidence that cytokines such as tumor necrosis factor (TNF) alpha, interleukin (IL) 1beta, IL-6, bone morphogenetic proteins (BMP), and nitric oxide (NO) play an important role in the pathogenesis of bone tunnel enlargement following anterior cruciate ligament (ACL) reconstruction. Furthermore, the release of these mediators has been considered a possible reason for the higher incidence of bone tunnel enlargement following hamstring tendon (HST) than following patellar tendon (PT) ACL reconstruction observed in several studies. In this investigation synovial fluid samples from 13 patients were collected immediately before (24+/-7 days after ACL rupture) and 7 days after ACL surgery and values of TNF-alpha, IL-1beta, IL-6, NO, and BMP-2 were analyzed. Furthermore, the incidence of bone tunnel enlargement was assessed using radiographs 38+/-7 weeks after surgery. Six patients underwent autologous HST ACL reconstruction, and in seven patients an PT autograft was used. In the overall patient population there were significantly higher synovial fluid concentrations of IL-6 and BMP-2 postoperatively than preoperatively; TNF-alpha showed a trend towards lower postoperative levels while IL-1beta and NO remained unchanged. The concentrations of NO, TNF-alpha, and IL-6 found in the present study were clearly higher than normal values given in the literature. Assessment of bone tunnel enlargement revealed an average increase in tibial tunnel width of 28.4+/-3.1% with comparable values for HST and PT ACL reconstructions. There was no significant correlation between bone tunnel enlargement and postoperative synovial fluid concentrations of TNF-alpha, IL-1beta, IL-6, NO, and BMP-2. However, all patients with bone tunnel enlargement had higher postoperative concentrations of TNF-alpha, IL-6, and NO in the synovial fluid. There were no significant differences in concentrations between HST and PT groups. In conclusion, we observed an association between tibial bone tunnel enlargement and elevated synovial fluid concentrations of IL-6, TNF-alpha, and NO 7 days after ACL surgery indicating the potential involvement of these biological mediators in the pathogenesis of bone tunnel enlargement. However, there was no difference between HST and PT ACL reconstructions regarding synovial fluid contents of IL-6, TNF-alpha, IL-1beta, NO, and BMP-2, suggesting a comparable biological response between these autografts following their use in ACL reconstruction.

Quantitative assessment of angiogenesis in murine antigen-induced arthritis by intravital fluorescence microscopy.

Inhibition of angiogenesis might be a therapeutic approach to prevent joint destruction caused by the overgrowing synovial tissue during chronic joint inflammation. The aim of this study was to investigate angiogenesis in the knee joint of mice with antigen-induced arthritis (AIA) by means of intravital microscopy. In 14 mice (C57BL6/129Sv) intravital microscopic assessment was performed on day 8 after AIA induction in two groups (controls, AIA). Synovial tissue was investigated by intravital fluorescence microscopy using FITC-dextran (150 kD). Quantitative assessment of vessel density was performed according to the following categories: functional capillary density (FCD, vessels <10 microm in diameter), functional vessel density (FVD, vessels >10 microm) and FVD of vessels with angiogenic criteria (convoluted vessels, abrupt changes of diameter, vessels which are generated by sprouting and progressively pruned and remodelled). Microvessel count was performed using immunohistochemistry. There was no significant difference in FCD between the control group (337 +/- 9 cm/cm2; mean +/- SEM) and the AIA group (359 +/- 13 cm/cm2). The density of vessels larger than 10 microm diameter was significantly increased in animals with AIA (135 +/- 10 vs. 61 +/- 5 cm/cm2 in control). The density of blood vessels with angiogenic criteria was enhanced in arthritic animals (79 +/- 17 vs. 12 +/- 2 cm/cm2 in control). There was a significant increase in the microvessel count in arthritic animals (297 +/- 25 vs. 133 +/- 16 mm(-2) in control). These findings demonstrate that angiogenesis in murine AIA can be assessed quantitatively using intravital microscopy. Further studies will address antiangiogenic strategies in AIA.

[The significance of immunology in orthopaedics today]. / Aktueller Stand der Immunologie in der Orthopädie.

Within the last years, basic science in immunology has been able to extensively increase the knowledge about the pathogenesis of many diseases. Although much hesitation persists, it has been possible to develop new immunomodulatory strategies which have proven their efficiency and safety in a number of clinical studies. Prior to that, a large number of in vitro and in vivo investigations have established a knowledge base for the development of drugs used in clinical settings. In orthopedic diseases, these immunomodulatory strategies are directed mainly towards the treatment of rheumatoid arthritis and osteoarthritis. Furthermore, immunotherapeutic approaches to bone and soft tissue tumor/metastasis has been improved and we expect first clinical results soon. Moreover, improvement of our understanding of the pathogenesis of inflammation occurring in various diseases, such as aseptic loosening of endoprostheses might help identify a whole field of orthopedic problems as a target for immunomodulatory therapies. In this review, recent developments and applications of immunomodulation in orthopedics will be discussed and a view into the future of such therapies will be given.

[Chronic recurrent multifocal osteomyelitis]. / Chronisch rekurrierende multifokale Osteomyelitis. Kasuistik einer 25-jährigen Patientin mit sternospondylärem Befall.

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, inflammatory, skeletal disease of unknown origin, which mainly affects children and adolescents in terms of cleido-spondylo-metaphysal skeletal inflammation. Only 10% of the patients are older than 20 years. To date, only about 200 cases have been reported in the literature. In the course of the disease, the initial radiological signs are osteolysis followed by sclerosis and hyperostosis in the end stage. The histological investigations reveal chronic inflammatory infiltrates with lymphocytes and hyperostosis. Although the prognosis of CRMO, to our current understanding, is self limiting, serious complications have been reported such as pathological fractures and compression fractures of the spine. A recently recommended therapy scheme is based on the administration of azithromycin combined with calcitonin. We present the case of a 25 year old female patient who has suffered from CRMO for 1.5 years with the cervical spine and the manubrium sterni being affected. The current state of diagnosis, therapy, and prognostic outlook of this rare disease are discussed.

Effects of ibandronate on inflammation in mouse antigen-induced arthritis.

OBJECTIVE: To investigate the effects of ibandronate, a novel aminobisphosphonate, on inflammation as well as leukocyte-endothelial cell interaction in mouse antigen-induced arthritis (AiA). MATERIAL AND TREATMENT: 36 Balb/c mice were subcutaneously injected with 160 microg/kg of ibandronate once per day beginning at day 7 until day 13 after induction of AiA. METHODS: The severity of arthritis was assessed by changes of the transverse knee joint diameter. For the intravital fluorescence microscopy measurements on day 14 after AiA induction, the patella tendon was partly resected to visualize the intraarticular synovial tissue of the knee joint. The number of rolling and adherent leukocytes as well as red blood cell (RBC) velocity and functional capillary density (FCD) were quantified in synovial microvessels. Furthermore, leukocyte infiltration in the synovium was determined in histological sections with an established score. RESULTS: Both fractions of rolling leukocytes (p = 0.016) as well as number of extravasated leukocytes (p = 0.004) were enhanced in control animals treated with ibandronate in comparison to animals which received saline. Arthritic animals with and without ibandronate treatment revealed an increased FCD (p = 0.006, p = 0.008), enhanced number of rolling ( p = 0.002, p = 0.001) and adherent leukocytes (p = 0.009, p = 0.007) and greater swelling of the left knee joint (p = 0.002, p = 0.001) when compared to control animals. No significant differences between arthritic animals and arthritic animals treated with ibandronate were found in any of the parameters assessed including leukocyte adherence, FCD, histology, and knee joint swelling. CONCLUSION: Ibandronate treatment of healthy mice was associated with an enhanced fraction of rolling leukocytes and increased numbers of extravasated leukocytes indicating a proinflammatory effect on the synovial microcirculation. In animals with a preexisting antigen-induced arthritis, however, ibandronate did not induce an exacerbation of joint inflammation and leukocyte adherence.

[Inflammatory responses to wear particles in vivo: a novel model in the murine knee joint]. / Inflammatorische Reaktion auf Abriebpartikel von Endoprothesen in vivo. Ein experimentelles Modell an der Maus.

Although it is now widely recognized that the inflammatory response to implant wear particles plays an important role in aseptic loosening of total joint replacements, the precise mechanisms of this process remain unclear. The aim of this study was to establish an animal model for the study of the adverse response to particulate wear debris and the effects on the synovial microcirculation as well as the leukocyte-endothelial cell interaction in the murine knee joint in vivo. Balb/c mice were injected with 50 microl of a 0.5-microm polystyrene particle suspension (0.1% v/v) into the knee joint. The severity of the inflammatory response was evaluated at days 1, 2, 3, 5, 7 (acute), 21 (intermediate), and 63 (chronic) after particle injection. Histological examination as well as assessment of the synovial microcirculation using intravital microscopy was performed. For the intravital microscopy measurements, the patella tendon was partially resected for visualization of the synovial tissue of the knee joint and the fluorescent markers FITC-dextran and rhodamine 6G were injected intravenously. There was a significantly enhanced leukocyte-endothelial cell interaction beginning at day 3 after particle injection with a maximum in the acute phase (days 5-7) and a subsequent decline in the intermediate (day 21) and chronic (day 63) phases. Functional capillary density was significantly increased from day 3 until day 21 after particle application. The histological examination showed an inflammatory reaction that complied widely with the temporal course of the microvascular parameters and resembled the histological appearance of the synovial-like membrane around loose joint prostheses. A novel model was established for the qualitative and quantitative investigation of the particle-induced inflammatory response in the joint environment. It was shown for the first time that there is a significantly enhanced leukocyte-endothelial cell interaction in the synovial tissue after intra-articular particle injection. This model seems to be suitable for further investigations, e.g., dealing with the biocompatibility of different particle materials.

[Metal-on-metal pairs for hip prostheses]. / Die Metall-Metall-Paarungen für den künstlichen Hüftgelenkersatz.

Due to engineering deficiencies as well as problems in the basic material, the first generation of metal-on-metal hip prostheses was not up to standard.Furthermore, unsatisfying clinical results led to a decrease in the use of these prostheses.Nevertheless, there were several cases which demonstrated good results in long-term clinical outcome. After distinct improvements in manufacturing and materials, metal-on-metal prostheses have made a come back. This second generation, which are known mainly under the names METASUL and SIKOMET,have been in clinical use for up to 10 years and the good results found in biomechanical set ups seem to be confirmed in clinical trials. However, a possible disadvantage of this second generation of metal-on-metal hip prostheses might be the production of large amounts of particulate wear debris in the nanometer size range. Whether the great number of small size particles with an extended metal surface and the possible distribution of these particles in the body have biological effects on the cells and tissues (such as allergic or toxic reactions) remains unknown. Among the tribological problems, there is currently a discussion on the possible inflammatory effect of these metal particles, which might play a crucial role in longterm, systemic reactions of the body to metal particles.

Differential function of nitric oxide in murine antigen-induced arthritis.

BACKGROUND: The aim of our study was to investigate the role of inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) production in different stages of murine antigen-induced arthritis (AiA). METHODS: Clinical, histological and microcirculatory parameters (measured by intravital fluorescence microscopy) were assessed in the knee joint during acute and chronic AiA after inhibition of iNOS with L-N(6)-(1-iminoethyl)lysine (L-NIL). Plasma concentrations of and were evaluated by the Griess reaction and the expression of iNOS, P- and E-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) by immunohistochemistry. RESULTS: In both stages of the disease, plasma concentrations of and were increased and iNOS was expressed. In the acute phase, swelling, leucocyte adhesion, leucocyte infiltration and expression of adhesion molecules were increased in arthritic animals treated with L-NIL in comparison with untreated arthritic animals. In the chronic phase, no change in the disease parameters could be detected after L-NIL treatment. CONCLUSION: Increased NO production induced by iNOS during the acute phase of AiA can be regarded as a protective response in the prevention of further leucocytic infiltration and joint destruction, whereas it seems to play a subordinate role in chronic AiA.