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Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 476 - 476
1 Jul 2010
Korsching E Liva S Barillot E Cleton-Jansen A Neumann A Schuch R Bürger H Agelopoulos K
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The concept of translational research is always hampered by the problem that most of the disease phenotypes do not have a mono causal origin. Therefore most treatment schemes based on one to three drugs are not really productive for most of the patients even if the patients are carefully selected from the responder group. Here the array techniques has inspired many research groups to develop algorithms deriving interaction networks or regulatory networks from this type of data to better get rid of the complexity of the biochemical interactions. The challenge is to find networks and to select the group of master nodes which might be good targets for a balanced multi-drug treatment. This means not only to measure one data type with array techniques but to join array data from multiple platforms and different data levels. Our goal is to integrate these data types to form networks with a predictive character for osteosarcomas.

The existing web platform CAPweb/VAMP from the Institute Curie is based on a Java web-client and R. This platform is focused on array data analysis and visualisation, can be extended by additional R modules and is therefore an excellent choice to implement further algorithms for data integration and network prediction. We are now establishing algorithms beyond a pure association of effects like permutation procedures for optimal rank orders of effects in a given subset of 16 factors which can be assembled to bigger units and selection procedures of gene expression signals by gene dosage concepts.

The presented approach is sustainable because the platform can be constantly extended and improved. On the other hand this platform is end-user suitable. This is the best way to bring theoretical concepts to the bench scientist. As a consequence translational research will become more real and complex systems more feasible.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 464 - 464
1 Jul 2010
Neumann A Korsching E Cleton-Jansen A Duim R Bürger H Agelopoulos K
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Osteosarcoma (OS) is the most common primary malignancy of bone, with up to 80% of patients suffering from metastatic or micrometastatic disease at the time of diagnosis. For the metastatic potential of tumours invasiveness plays an important role. This study intends to determine new candidate genes for cell invasiveness.

Eight OS cell lines (MNNG, HOS, MG63, SJSA1, OST, ZK58, U2OS, SAOS) were analysed using a modified Boyden Chamber Assay to separate invasive and non-invasive cells. Total RNA isolation and Illumina hybridisation Arrays (V3 bead arrays) were performed for both fractions.

Out of the eight cell lines, five (MNNG, HOS, MG63, SJSA1, OST) displayed an invasive fraction between 1.76 and 0.02%, which proved sufficient for subsequent RNA analysis. Pair wise comparison yielded 161 differently expressed genes between invasive and non-invasive cells. These are involved in important pathways such as cell motility, cell communication or signal transduction.

The generated new candidate genes might play an important role in metastasis of OS. Their functional characterization has been started combining knockdown experiments (RNAi) with the invasion assay. Validation will be done by RT-PCR and immunohisto-chemistry on a larger sample using OS-TMAs. Determined genes and pathways will be correlated with clinical parameters like metastasis, survival and chemotherapy sensitivity in order to improve understanding of the biology of OS.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 440 - 440
1 Jul 2010
Balke M Neumann A Agelopoulos K Korsching E Hardes J Kersting C Buerger H Gosheger G Hagedorn M
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Because of the lack of a suitable in vivo model for giant cell tumors of bone little is known about their biological behavior and mechanisms of metastasis. No existing cell line contains all tumor components, so that testing of anti tumor agents is hardly possible. We therefore modified the chick chorio-allantoic membrane (CAM) assay for giant cell tumor of bone (GCTB).

Out of tumor tissue obtained during surgery of 5 patients a solution was produced. The solute was grafted onto the CAM at day 10 of embryonic development. The growth process was monitored by daily observation and photo documentation using in vivo microscopy. After 5 to 6 days of tumor growth the samples were fixed in formalin and further analyzed using standard histology (hematoxylin and eosin stains).

The tissue solute of all 5 patients formed solid tumors when grafted to the CAM. In vivo microscopy and standard histology revealed a rich vascularisation of the tumors. The tumors were composed of the typical components of GCTB including multinuclear giant cells.

A reliable protocol for grafting of human giant cell tumors onto the chick chorio-allantoic membrane was established. This model is the first in vivo model for giant cell tumors of bone. Further characterization of the growing tissue is necessary in further experiments.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_III | Pages 340 - 340
1 Mar 2004
Neumann A Schuster A Klemm S Mika J Reichlin S Christen B
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Aims: Fractures of the distal radius are one of the most frequent fractures in older patients. For treatment this fractures conservative and operative procedures are accept. It was the aim of this retrospective study to point out, clinical and economical advantages of the treatment with the radioradial þxateur externe against the conservative therapy and other operative treatments. Methods: Between September 1999 und December 2000 58 patientens (53 women/5 men), older than 65 years (78,4±8,1), with fractures of the distal radius were treated in our hospital. 50 patients were clinically and radiologically controlled. Results: AO-Classiþcation: A84%, B4%, C12%. 11 patients were treated conservative (group1), 21 patients treated with radio-radial þxation (group2), 17 patients with other osteosynthesis (group3). There were signiþcant differences in the dorsal tilt of the articular plane, proceed from a post-traumatic Δtilt at 25,7¡±8,1¡. The fractures were corrected on a Δtilt at 16,3¡±4,3¡(group1) vs. a Δtilt at -1,0¡±7,2¡(group2) vs. a Δtilt at 9,7¡±6,9¡(group3) (p< 0,001). Also after 12 months this difference was signiþcantly higher: 21,5¡±9,9¡ vs. 1,7¡±7,6¡ vs. 10,5¡±8¡ (p< 0,001). Likewise signiþcant difference was the estimation of the postoperative pain with the visual-pain-analog-scale: 18,4±13,6 vs. 6,6±8,8 (p< 0,05). The costs for ambulant nursing and housekeeping amount to 3500e in group1, in group2 1500e. Conclusions: The treatment of fractures of the distal radius in older patients with poor bone-quality with radio-radial þxateur externe represents a alternative by clinical and radiological good results. Improved motion conducts a clear mean expenditure of ambulant after-treatment. Because of the developing savings-potential and the better clinical and radiological results the radio-radial þxateur externe can be recommended as a cost-lowering and quality-securing treatment.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 193 - 194
1 Jul 2002
Mersich I Hartley R Neumann A Wallace W
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Shoulder surgery is associated with moderate to severe post-operative pain. A pain free post-operative period is desirable and appreciated by both patients and therapists and is essential for early rehabilitation. Analgesia can be provided either locally or systemically or by combining the two.

A prospective, randomised double blind study was designed to assess the effectiveness of an existing postoperative local analgesic method: using Marcaine through subacromial catheter.

Thirty-nine patients were included in the trial. All patients had simple arthroscopic subacromial decompression and no additional pathology to the shoulder. At the end of the operation a standard epidural catheter was inserted into the subacromial space under visual control. Sixteen patients had 0.25% Bupivacaine and 23 patients had normal Saline given in 10 ml boluses six hourly, until required. All patients had access to conventional pain relief (paracetamol, non-steroids, minor opioids, morphine). VAS scores were taken before and one hour after the study bolus was given. In addition the patients were assessed for quality of sleep, opinion about the analgesia provided by the catheter and VAS of pain prior to and post physiotherapy sessions. The physiotherapist also recorded the active forward flexion of the operated shoulder. The number of doses required and all additional analgesic medication were recorded.

The use of subacromial local anaesthetic provides significantly better pain relief (P=0.029). However, patients with subacromial local anaesthetic