[Spinal ozone therapy]. / Spinale Ozontherapie.

CLINICAL/METHODOLOGICAL PROBLEM: Technical advances in the field of spinal interventional neuroradiology allow the application of a wide range of targeted, minimally invasive treatment options including targeted spinal ozone therapy for back pain. This article provides an overview of the biochemical, molecular, immunologic, and pharmaceutical mechanisms and delivery techniques of targeted ozone therapy. STANDARD RADIOLOGICAL METHODS: Computed tomography (CT), conventional X­ray (fluoroscopy). PERFORMANCE: Computed tomography-guided interventions (epidural, periradicular, facet joint, and intradiscal) have the highest place value and have historically prevailed. Fluoroscopy-guided procedures may also be used. PRACTICAL RECOMMENDATIONS: Ozone therapy provides promising results. The article is intended to provide information on the basics of the technique(s).

[Spondylodiscitis and epidural abscesses]. / Spondylodiszitis und epiduraler Abszess.

CLINICAL/METHODOLOGICAL PROBLEM: Spondylodiscitis is an inflammation of the intervertebral disc, which in adults is generally associated with spondylitis of the adjacent vertebrae. It often presents clinically with nonspecific symptoms such as back or neck pain. It may be caused by various pathogens, especially bacteria. One or more vertebral segments can be affected. The infection can spread to surrounding compartments and can lead to epidural abscesses. Radiology, in particular magnetic resonance imaging (MRI), plays an important role in the diagnostic work-up and in the follow-up to monitor response to therapy. Treatment consists of conservative (antibiotics) and invasive approaches, including surgery. Interventional puncture and drainage is a promising alternative to surgery, especially in early stages of abscess formation. STANDARD RADIOLOGICAL METHODS: Magnetic resonance imaging (MRI), computed tomography (CT), nuclear medical procedures, conventional x­ray. PERFORMANCE: MRI has the highest value. CT and nuclear medical procedures can be used as a supplement to MRI and in patients with contraindications for MRI. PRACTICAL RECOMMENDATIONS: With adequate diagnosis and therapy, spondylodiscitis has a good prognosis. In addition to targeted or calculated drug therapy, invasive treatment is the main focus, especially for epidural abscesses. Interventional radiological drainage can represent a less invasive alternative to surgical treatment.

Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: A guideline by the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU).

BACKGROUND: Autologous chondrocyte implantation (ACI) is an established and well-accepted procedure for the treatment of localised full-thickness cartilage defects of the knee. METHODS: The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning therapeutic consequences of primary cartilage lesions and the suitable indication for ACI. RESULTS: Based on best available scientific evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than three to four square centimetres; in the case of young and active sports patients at 2.5cm(2), while advanced degenerative joint disease needs to be considered as the most important contraindication. CONCLUSION: The present review gives a concise overview on important scientific background and the results of clinical studies and discusses the advantages and disadvantages of ACI. LEVEL OF EVIDENCE: Non-systematic Review.

Alternation of histone and DNA methylation in human atherosclerotic carotid plaques.

Little is known about epigenetics and its possible role in atherosclerosis. We here analysed histone and DNA methylation and the expression of corresponding methyltransferases in early and advanced human atherosclerotic carotid lesions in comparison to healthy carotid arteries. Western Blotting was performed on carotid plaques from our biobank with early (n=60) or advanced (n=60) stages of atherosclerosis and healthy carotid arteries (n=12) to analyse di-methylation patterns of histone H3 at positions K4, K9 and K27. In atherosclerotic lesions, di-methylation of H3K4 was unaltered and that of H3K9 and H3K27 significantly decreased compared to control arteries. Immunohistochemistry revealed an increased appearance of di-methylated H3K4 in smooth muscle cells (SMCs), a decreased expression of di-methylated H3K9 in SMCs and inflammatory cells, and reduced di-methylated H3K27 in inflammatory cells in advanced versus early atherosclerosis. Expression of corresponding histone methyltransferases MLL2 and G9a was increased in advanced versus early atherosclerosis. Genomic DNA hypomethylation, as determined by PCR for methylated LINE1 and SAT-alpha, was observed in early and advanced plaques compared to control arteries and in cell-free serum of patients with high-grade carotid stenosis compared to healthy volunteers. In contrast, no differences in DNA methylation were observed in blood cells. Expression of DNA-methyltransferase DNMT1 was reduced in atherosclerotic plaques versus controls, DNMT3A was undetectable, and DNMT3B not altered. DNA-demethylase TET1 was increased in atherosclerosisc plaques. The extent of histone and DNA methylation and expression of some corresponding methyltransferases are significantly altered in atherosclerosis, suggesting a possible contribution of epigenetics in disease development.

[Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: a guideline by the working group "Tissue Regeneration" of the German Society of Orthopaedic Surgery and Traumatology (DGOU)]. / Stellenwert der autologen Chondrozytentransplantation (ACT) in der Behandlung von Knorpelschäden des Kniegelenks - Empfehlungen der AG Klinische Geweberegeneration der DGOU.

Autologous chondrocyte transplantation/implantation (ACT/ACI) is an established and recognised procedure for the treatment of localised full-thickness cartilage defects of the knee. The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning potential consequences of primary cartilage lesions and the suitable indication for ACI. Based on current evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than 3-4 cm2; in the case of young and active sports patients at 2.5 cm2. Advanced degenerative joint disease is the single most important contraindication. The review gives a concise overview on important scientific background, the results of clinical studies and discusses advantages and disadvantages of ACI.

Iso-C/3-dimensional neuronavigation versus conventional fluoroscopy for minimally invasive pedicle screw placement in lumbar fusion.

BACKGROUND: Minimally invasive spinal surgery (MISS) has evolved over the past years due to the combination of microsurgery, minimal access strategies and neuronavigation. Percutaneous or mini-open pedicle screw placement is a challenge, especially for surgeons not experienced in the use of biplanar fluoroscopy or stereotactic imaging techniques. The aim of the study was to compare the precision of pedicle screw fixation for lumbar fusion procedures using Iso-C/stereotactic 3D neuronavigation (3D NAV) vs. standard AP/lateral fluoroscopy (2D NAV). METHODS: Our first 42 patients undergoing MISS for one- or 2-level lumbar or lumbosacral fusion procedures for degenerative lumbar pathology were included in this study. Either 3D NAV (n=29) or standard fluoroscopy (n=13) was used to aid screw placement. Demographics, operative time, blood loss, and screw placement accuracy were evaluated. Screw placement was evaluated postoperatively using lumbar CT scanning. Accuracy of 3D NAV was evaluated by comparing intraoperative planning screenshots to postoperative CT placement of screws. RESULTS: There were no significant differences between groups for mean age, gender or intraoperative blood loss. 90.9% of 3D NAV screws and 73.7% of fluoroscopy screws had no pedicle perforation (p=0.04). Intraoperative navigation screenshots accurately predicted pedicle screw placement in 90.9% of cases. There was a positive correlation between 3D NAV accuracy and better screw grade (rs 0.45, p=0.036). CONCLUSIONS: Utilization of 3D NAV for percutaneous or mini-open lumbar screw placement during the early learning curve for MISS was associated with higher screw accuracy. This study demonstrates that the use of 3D navigation can facilitate the learning curve for MISS.

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.

[Quality improvement of resources in radiology on the internet]. / Qualitätsverbesserung radiologischer Lehrressourcen im Internet.

PURPOSE: Categorization and evaluation of online teaching files in radiology by representative members of the target group to make the specific search for adequate programs more effective. MATERIALS AND METHODS: A representative team of board qualified radiologists, residents and medical students performed a basic search for radiology teaching files on the Internet using search machines, international mailing lists and link lists to collections of national and international radiological societies and departments. The programs were categorized by language, modality, target group and special features, such as qualification for CME-accreditation. For final evaluation and ranking of the detected files, a questionnaire was developed to assess completeness, image quality, page loading time, layout, orientation, interactivity, annotation and maintenance. The results were stored in an Access database on a web server. A query form in HTML format, including the parameters described above, was made accessible to the online user. RESULTS: A search machine for radiological teaching files (RadList/Entity-link List) was made available online ( www.tnt-radiology.de/radlist and www.tnt-radiology.de/entitylinklist ). A submitted request calls a cgi script that searches the database for the appropriate sites according to the individual search parameters selected by the user. The list of matching URLs is returned to the user as HTML page. Evaluating the single sites by applying the criteria listed above contributed to the quality assurance of the radiological teaching resources on the Internet. CONCLUSION: Adapting a new Internet interface to the particular needs of the user allows a more effective access to specific radiological teaching files online. RadList/Entity-link List ( www.tnt-radiology.de/radlist and www.tnt-radiology.de/entitylinklist ) is conducive to quality improvement and benefits users as well as authors of radiological teaching files on the Internet.

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.

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.

[Web-based training in radiology - student course in the Virtual University of Bavaria]. / Web-basiertes Training in der Radiologie - Studentenkurs in der Virtuellen Hochschule Bayern (VHB).

PURPOSE: The ninth version of the licensing regulation for medical doctors (Approbation Regulation (AR)) sets a benchmark in terms of practical experience, interdigitation of preclinical and clinical studies, interdisciplinary approach, economic efficiency, independence of students, added new teaching and learning modalities, and ongoing evaluation of the progress of the medical students. It is the aim to implement these major points of the AR in a model course for diagnostic radiology and radiation protection within the scope of the Virtual University of Bavaria and test them in practice. MATERIALS AND METHODS: In cooperation with residents and board certified radiologists, students developed the virtual course "Web-Based Training (WBT) Radiology" in diagnostic radiology and radiation protection for students in the first clinical semester. A representative target group taken from the student body was asked about the options to get access to the World Wide Web (Internet), and the satisfaction concerning configuration and content of the newly developed program. A comparison was made between the results of the final examination taken by students who made use of the virtual course in addition to conventional lessons and taken by students who did not subscribe to the virtual course and exclusively relied on conventional lessons. In addition, a pilot study was conducted in the winter semester 2002/03, which compared students taking either the traditional lessons or the new virtual course on the Internet. RESULTS: The virtual course-model had test results with a positive trend. All targeted students had Internet access. Constructive criticism was immediately implemented and contributed to rapid optimization. The learning success of the additive or alternative virtual course was in no way less than the learning success achieved with the conventional course. CONCLUSION: The learning success as measure of quality in teaching and the acceptance by students and teachers justify the continuation of this course model and its expansion. Besides enabling the learning in small study groups; the course "WBT Radiology" might not only help implementing the major points of the new AR but might also complement any deficiencies in the current education. Economic aspects may encourage their implementations.

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.

Epithelial ion transport in the ileal J-pouch after proctocolectomy in the rat.

In ulcerative colitis and polyposis coli, creation of an ileal pouch with ileoanal anastomosis after proctocolectomy has become a common surgical method. The aim of our study was to characterize the adaptation of the epithelial ion transport function in the pouch by using electrophysiologic techniques. Proctocolectomy and ileoanal anastomosis was performed in rats either with (pouch) or without (control) creation of an ileal J-pouch. To characterize the epithelial barrier function, impedance analysis was performed 6 months after surgery. Epithelial resistance was 29 +/- 2 omega.cm2 in controls and was unchanged in the pouch (28 +/- 4 omega.cm2; NS). In contrast, subepithelial resistance increased from 33 +/- 3 omega.cm2 to 54 +/- 5 omega.cm2 (P < 0.01) owing to work hypertrophy of the muscle layers in the pouch. To detect changes in net ion transport, ion tracer fluxes were measured in the Ussing chamber. In control ileum, absorptive net Na and Cl fluxes of similar magnitude were present, indicating that electroneutral NaCl absorption was the predominant ion transport system. Neither Isc nor net Na and Cl fluxes were significantly altered in the pouch. Glucose-coupled Na absorption was measured as the 3-o-methyl-glucose-induced increase in Isc. Km remained unaltered, while Vmax decreased from 7.5 +/- 2.1 mu eq.h-1 cm-2 in controls to 1.7 +/- 0.8 mu eq.h-1 cm-2 (P < 0.05) in the pouch. Then, maximal transport capacity for electrogenic Cl secretion was measured as the Cl-induced increase in Isc blockable by serosal bumetanide (in the presence of theophylline and prostaglandin E1).(ABSTRACT TRUNCATED AT 250 WORDS)