Varying development of femoral and tibial subchondral bone tissue and their interaction with articular cartilage during progressing osteoarthritis.

INTRODUCTION: Differences between tibial and femoral joint surfaces and knee compartments concerning coupled bone and cartilage turnover or bone-cartilage cross talk have not been previously examined, although the mechanical and biological interaction of the mineralized subchondral tissues with articular cartilage is of great importance for advancing osteoarthritis. MATERIALS AND METHODS: Therefore, with the help of immunohistochemistry and real-time polymerase chain reaction (RT-PCR), human knee joint cartilage tissue was investigated for expression of key molecules of the extracellular matrix and cartilage composition (collagen type I and II, aggrecan) plus proteoglycan content (colorimetric analysis). Furthermore, we correlated the results with 3D microcomputed tomography of the underlying subchondral bone (high-resolution micro-CT system). Measurements were performed in dependence of the anatomical site (femoral vs. tibial, medial and lateral each) to identify regional differences during the osteoarthritic process. From an enduring series of 108 patients undergoing implantation of TKA, 34 osteochondral samples with lesions macroscopically classified as ICRS grade 1b (group A) and 34 samples with ICRS grade 3a/3b lesions (group B) were compared with 21 healthy controls. RESULTS: Concerning 3D analysis, the medial femoral condyle and tibia showed the most significant increase in bone volume fraction and a decrease in the trabecular number in group B frequently accompanied by subchondral bone resorption pits and enchondral ossification. Under physiological conditions, tibia plateaus show lower bone volume fraction than the corresponding femoral site and this difference enlarges with advancing OA. Partially even contradictory behavior was observed such as trabecular separation at the lateral tibial and medial plateau in osteochondral OA samples of the same patients. Collagen type II expression levels show faster and varying changes than type I during the OA process, leading to a lower positive or negative correlation with bone microstructural analysis, especially on the tibia plateau. CONCLUSIONS: Structural bone and cartilage parameter changes showed varying developments and correlations among each other in the different compartments of the knee. As a clinical conclusion, therapies to postpone or prevent cartilage degeneration by influencing the loss of mineralized bone could be site dependent.

[Tumours and metastases of the spine : cavity/coblation surgery and vertebroplasty/kyphoplasty]. / Tumoren und Metastasen an der Wirbelsäule : Cavity/Coblation-Operation und Vertebro-/Kyphoplastie.

BACKGROUND: Radical surgery for metastases in the spine is in many cases not possible, includingthe higher risk of surgery in older patients with co-morbidities. The aims of treatment are: minimally invasive and maximally effective tumour removal, fracture position, stabilization, pain reduction, and improved quality of life. The specific features and problems of diagnosis and treatment using the cavity/coblation method, , the surgical technique, and the results of the treatment of 250 patients with spinal tumours/metastases are presented. MATERIALS AND METHODS: Tumour resection is carried out by plasma field, via percutaneous trans-/extrapedicular access, followed by kyphoplasty. Clinical and radiological follow-up was carried out postoperatively, including data on pain reduction and improvement of quality of life. RESULTS: Within 6 years (March 2008t February 2014) a total of 250 patients, or 812 spines were treated. In 59 cases dorsal percutaneous instrumentation and straightening were carried out. Minimal blood loss and a very low complication rate were recorded. After surgery, significant pain reduction, satisfaction, early mobilization, and improvement in quality of life were demonstrated in all patients. Immediate radio- and chemotherapy could be carried out. In 38 cases cement escaped laterally into the intervertebral space, but this had no clinical relevance. 188 patients have since died because of tumour manifestations. CONCLUSIONS: The cavity/coblation method has been demonstrated to be a safe, minimally invasive procedure, with good short- and long-term results and lower complication rates. A comprehensive diagnostic, including tumour staging, the correct indication, and prognosis estimation, is important.

An economic analysis of aseptic revision hip arthroplasty: calculation of partial hospital costs in relation to reimbursement.

INTRODUCTION: Aseptic loosening is one of the most common intermediate and long-term complications after total hip replacement (THR). These complications cause suffering and require expensive revision surgery. Little concrete data on direct costs are available from the hospital's, moreover operating department's perspective. We here provide a detailed analysis of the costs of THR revision and relate them to reimbursement underlying the German diagnosis-related groups (DRG) system. MATERIALS AND METHODS: Major cost parameters were identified using for orientation the cost matrix of the German Institute for Hospital Reimbursement (InEK GmbH). We then retrospectively analysed the major direct costs of aseptic revision THR in terms of contribution margins I and II. The analysis included a total of 114 patients who underwent aseptic revision from 1 January 2009 to 31 March 2012. Data were retrieved from the hospital information system and patient records. All costs of surgery, diagnostic tests, and other treatments were calculated as purchase prices in EUR. The comparative analysis of direct costs and reimbursements was done for DRG I46A and I46B from the hospital's, especially treating department's rather than the society or healthcare insurance's perspective. RESULTS: The average direct cost incurred by the hospital for a THR revision was 4,380.0. The largest share was accounted for surgical costs (62.7 % of total). Implant and staff costs were identified as the most important factors that can be influenced. The proportion of the daily contribution margin that was left to cover the hospital's indirect cost decreased with the relative cost weight of the DRG to which a patient was assigned. CONCLUSION: Our study for the first time provides a detailed analysis of the major direct case costs of THR revision for aseptic loosening from the provider's perspective. Our findings suggest that these revision operations could be performed cost-beneficially by the operating unit. From an economic perspective, cases with higher cost weights are more favorable for a hospital. These results need to be confirmed in multicenter studies.

[2010 Love Parade in Duisburg: clinical experiences in planning and treatment]. / Loveparade 2010 Duisburg - klinische Erfahrungen in Vorbereitung und Versorgung.

BACKGROUND: Tragic incidents at the 2010 Love Parade attracted significant public attention. As the frequency of similar events increases, more hospitals and practitioners will face the necessities of planning and response to unforeseeable occurrences. Obligatory guidelines for physicians do not exist, so that essential aspects are repeatedly discussed for each new event. This paper summarizes the experience of hospitals and emergency departments and draws conclusions, allowing recommendations for reasonable proposals for hospitals and practitioners. METHODS AND MATERIAL: A structured analysis of data concerning planning, patient flow and injury statistics led to a profile determining personnel, rooms and material which have to be provided by the hospitals. In a consensus conference afterwards and personal interviews with clinical coordinators the preparation of hospitals was evaluated to separate reasonable from needless efforts. RESULTS: We describe various measures concerning staff, logistics and rooms from the viewpoint of actual application. Reasonable measures for preparation and management of mass panic are analysed and described in detail. Problems are explained and solutions discussed. The result is a qualitative catalogue, which supports the organization of future events. CONCLUSION: Knowledge and reflection on the experience of the 2010 Love Parade optimizes local emergency guidelines and planning for similar events. A coordinated cooperation of all involved is essential.

[Relevance of different sequences in MRI-detected subchondral bone damage of the knee joint and possible therapeutic options]. / Relevanz unterschiedlicher MRI-Sequenzen bei subchondralen Verletzungen des Kniegelenkes und mögliche therapeutische Konsequenzen.

With the advent of magnetic resonance imaging (MRI) after knee injuries interest has focussed on the clinical relevance of different concomitant osseous damage. Different MRI- sequences reveal varying characteristics of such lesions. Prospective data of 69 patients with MRI-detected sub-acute subchondral fractures or bone bruises according to the classification of Mink was recorded. Function, symptoms (Noyes) and activity (Tegner) were assessed at the time of first MRI and 7,4 months later including a follow-up MRI using T 2-weighted fat saturated (fs) fast-spin-echo-sequences (FSE), T 1-weighted spin echo (SE) sequences, Proton-density-weighted spin echo-sequences (SE) and T 2-weighted (fs) gradient-echo-sequences. The patients were divided in 4 groups: patients with subchondral fracture and patients with pure bone bruise subdivided in patients with and without intraarticular knee lesions. Bone bruises were diagnosed in 44 cases, subchondral fractures in 25 patients. Patients without intra-articular pathology had significantly poorer function at the time of MRI with subchondral fractures, but not in the sub-group with intra-articular damage. Symptoms were not significantly different in both groups at this time. At 7,4 months both sub-groups with fractures had a lower level of function compared to patients with bone bruises, activity score and symptoms showed poorer results in the group without intraarticular lesion (p = 0,01 for all scores). T 1- weighted spin echo (SE) sequences revealed to be the most important tool to differentiate the various lesions. Hints for a modification of rehabilitation avoiding axial forces in case of subchondral fractures might be the use of isokinetics using open kinetic chain instead of closed kinetic chain or orthosis with relief of the affected compartment.

Regional differences of tibial and femoral cartilage in the chondrocyte gene expression, immunhistochemistry and composite in different stages of osteoarthritis.

The function of articular cartilage as an avascular tissue is mainly served by collagen type II and proteoglycan molecules. Within this matrix homeostasis between production and breakdown of the matrix is exceptionally sensitive. The current study was conducted to identify regional differences in specific alterations in cartilage composition during the osteoarthritic process of the human knee joint. Therefor the changes in the expression of the key molecules of the extracellular matrix were measured in dependence of the anatomical side (femoral vs tibial) and associated with immunohistochemistry and quantitative measurement. 60 serial osteochondral femoral condyle and the tibial plateau samples of patients undergoing implantation of total knee endoprosthesis of areas showing mild (Group A, macroscopically ICRS grade 1b) respectively advanced (Group B, macroscopically ICRS grade 3a/3b) (30 each) osteoarthritis according to the histological-histochemical grading system (HHGS) were compared with 20 healthy biopsies with immunohistochemistry and histology. We quantified our results on the gene expression of collagen type I and II and aggrecan with the help of real-time (RT)-PCR. Proteoglycan content was measured colorometrically. In group A slightly increased colour intensity was found for collagen II in deeper layers, suggesting a persisting but initially still intact repair process. But especially on the medial tibia plateau the initial Col II increase in gene expression is followed by a decrease leading to the lowest over all Col II expression on the medial plateau, here especially in the central part. There in late stage diseases the collagen type I expression was also more pronounced. Markedly decreased safranin O staining intensity was observed in the radial zone and less reduced intensity in the transitional zone with loss of zonal anatomy in 40% of the specimens in group A and all specimens in group B. Correlation between colorometrically analysed proteoglycan GAG content and aggrecan Real Time PCR is mainly weak. Tibial and femoral cartilage in contrast to patellar cartilage both are preferential exposed to compressive stresses, but presence of menisci affects the load distribution at the tibial side, which creates varying conditions for the different cartilage surfaces in the knee. As directly measured Poissons ratio in tibial cartilage is higher but Younǵs modulus is lower than in femoral cartilage, different resulting feedback amplification loops interact with proceeding cartilage damage. The initial loss of aggrecan may support Matrix metalloproteinases (Mmps) in the access to the collagen network and the considerably differing mechanical properties at both joint surfaces result in varying increased synthesis and release of matrix degrading enzymes. The present study has identified a selection of events which reflect the response of cartilage structure and composite, chondrocytes itself and their productivity to changes in mechanical stress depending on the anatomical site.

Regression and correlation analysis of preoperative versus intraoperative assessment of axes during navigated total knee arthroplasty.

OBJECTIVE: Modern computer assisted surgery (CAS) systems allow accurate positioning of the implants in navigated Total Knee Arthroplasty (TKA). However, when an operation is performed with a navigation system, it is important to know if the anatomical situation of the knee is reflected equally in both the preoperative image (e.g., CT) and the intraoperative navigation setup. In this study, we compared the preoperative anatomical situation to the virtual intraoperative situation of the navigation setup. MATERIAL AND METHODS: We analyzed 24 navigated operations. Intraoperatively, the condylar twist angle (CTA) was documented with the navigation system by measuring the angle between the transepicondylar axis (TEA) and posterior condyle axis (PCA). This data was compared with the preoperative data from the CT scan. RESULTS: Statistical analysis revealed that there was no correlation between the pre- and intraoperative data (r = 0.095). CONCLUSIONS: Statistically, there is no possibility of collecting the same angles and axes when using the two different methods (CT and navigation) on the same knee. It is not possible to copy the preoperative anatomical situation exactly with the virtual intraoperative data. Reasons for this include systematic errors, as well as inter- and intraobserver errors in both methods.

[Important Aspects of Diagnosis and Minimally Invasive Treatment of Metastases in the Spine Through the Plasma Field Therapy (Cavity Coblation Method)]. / Besonderheiten der Diagnostik und der minimalinvasiven chirurgischen Behandlung von multiplen Metastasen an der Wirbelsäule durch Plasmafeldtherapie (Cavity-Coblation-Methode).

Background and objectives: Until recently, it was almost impossible to perform major surgery on metastases in the spine. This is especially the case for multiple spinal metastases and for older multi-morbid patients with higher OP risks. It is very important in such cases that the operation should be as minimally invasive as possible, and should aim to reduce pain, treat fractures and to improve the quality of life. The aim of this publication is to present and discuss the specific features of the methodology, problems, surgical techniques, as well as the effectiveness of the modernised cavity/coblation method and results of the treatment of 240 patients with spine metastases. Patients/Material and Method: Patients: Patients of every age with bone destruction were treated, with osteolysis and pathological fractures of vertebrae caused by metastases. The pre-operative diagnosis was evaluated by X-Ray, MRT, CT, whole-body F18-FDG-PET, whole-body bone scintigraphy, histology. Cavity/coblation method: Tumour resection was carried out by the plasma field (42 °C, cold energy) over the percutaneous trans-/extrapedicular access and was followed by balloon kyphoplasty. Tumour tissue was removed, deformation corrected and stability enhanced. The treatment clearly reduced the risks of recurrence, fracture and compression of the neural structures. Local radiotherapy and chemotherapy were performed post-operatively. Clinical and radiological follow-ups, included tumour staging, were performed regularly after the OP (after 2 and 14 days and 3, 6,12, 24, 36, 48 and 60 months), including data on pain and improvement in quality of life. Results: Within 6 years (03/08-04/14), we treated 240 patients with multiple spinal metastases (146 female, 94 male, age range 31-92 years, average age 65.5 years) or 784 vertebral bodies. 61 patients were also given dorsal percutaneous instrumentation and straightening. All patients experienced a significant reduction in pain, and improvements in satisfaction and quality of life. Treatment was combined with chemotherapy and local radiotherapy to reduce tumour cell growth or recurrence rate. Patients could be rapidly mobilised after surgery, blood loss was minimal, and the next oncology treatment could be initiated immediately. Discussion/Conclusions: Cavity/coblation is a safe and minimally invasive procedure, as confirmed by our own short- and long-term results, as well as by reports/publications of other workers. OP risks, blood loss, and surgical time are lower and shorter. This new method is very promising for the future. It is important that the indication is correct and the treatment strategy must be adapted individually. Prognosis must be assessed and the surgical technique must be precise.

DNase I-induced DNA conformation. 2 A structure of a DNase I-octamer complex.

The structure of a complex between DNase I and d(GCGATCGC)2 has been solved by molecular replacement and refined to an R-factor of 0.174 for all data between 6 and 2 A resolution. The nicked octamer duplexes have lost a dinucleotide from the 3' ends of one strand and are hydrogen-bonded across a 2-fold axis to form a quasi-continuous double helix of 14 base-pairs. DNase I is bound in the minor groove of the B-type DNA duplex forming contacts in and along both sides of the minor groove extending over a total of six base-pairs. As a consequence of binding of DNase I to the DNA-substrate the minor groove opens by about 3 A and the duplex bends towards the major groove by about 20 degrees. Apart from these more global distortions the bound duplex also shows significant deviations in local geometry. A major cause for the observed perturbations in the DNA conformation seems to be the stacking type interaction of a tyrosine ring (Y76) with a deoxyribose. In contrast, the enzyme structure is nearly unchanged compared to free DNase I (0.49 A root-mean-square deviations for main-chain atoms) thus providing a rigid framework to which the DNA substrate has to adapt on binding. These results confirm the hypothesis that groove width and stiffness are major factors determining the global sequence dependence of the enzyme's cutting rates. The nicked octamer present in the crystals did not allow us to draw detailed conclusions about the catalytic mechanism but confirmed the location of the active site near H134 on top of the central beta-sheets. A second cut of the DNA induced by diffusion of Mn2+ into the crystals may suggest the presence of a secondary active site in DNase I.

Crystallisation and preliminary crystallographic analysis of P1 nuclease from Penicillium citrinum.

P1 nuclease, a zinc-dependent single-strand specific endonuclease from Penicillium citrinum, has been crystallized in three different space groups using either ammonium sulphate or polyethylene glycol 4000 as the precipitating agent. The crystals diffract to between 3 A and 2.2 A. A 4.5 A electron density map has been calculated for a tetragonal crystal form, based on a platinum derivative, and was improved by solvent flattening. The boundaries of the two molecules in the asymmetric unit are clearly visible in most regions and the presence of rod-like density features are indicative of a rather high alpha-helix content. The highest density peaks in the map were identified as a trinuclear zinc cluster present in each monomer by a difference Fourier of an EDTA-soaked crystal.

X-ray structure of the DNase I-d(GGTATACC)2 complex at 2.3 A resolution.

The crystal structure of a complex between DNase I and the self-complementary octamer duplex d(GGTATACC)2 has been solved using the molecular replacement method and refined to a crystallographic R-factor of 18.8% for all data between 6.0 and 2.3 A resolution. In contrast to the structure of the DNase I-d(GCGATCGC)2 complex solved previously, the DNA remains uncleaved in the crystal. The general architecture of the two complexes is highly similar. DNase I binds in the minor groove of a right-handed DNA duplex, and to the phosphate backbones on either side over five base-pairs, resulting in a widening of the minor groove and a concurrent bend of the DNA away from the bound enzyme. There is very little change in the structure of the DNase I on binding the substrate. Many other features of the interaction are conserved in the two complexes, in particular the stacking of a deoxyribose group of the DNA onto the side-chain of a tyrosine residue (Y76), which affects the DNA conformation and the binding of an arginine side-chain in the minor groove. Although the structures of the DNA molecules appear at first sight rather similar, detailed analysis reveals some differences that may explain the relative resistance of the d(GGTATACC)2 duplex to cleavage by DNase I: whilst some backbone parameters are characteristic of a B-conformation, the spatial orientation of the base-pairs in the d(GGTATACC)2 duplex is close to that generally observed in A-DNA. These results further support the hypothesis that the minor-groove width and depth and the intrinsic flexibility of DNA are the most important parameters affecting the interaction. The disposition of residues around the scissile phosphate group suggests that two histidine residues, H134 and H252, are involved in catalysis.

Bacteriophage lambda display of complex cDNA libraries: a new approach to functional genomics.

We describe the construction and characterization of two lambda surface displayed cDNA expression libraries derived from human brain and mouse embryo. cDNA inserts were obtained by tagged random-priming elongation of commercially available cDNA libraries and cloned into a novel lambda vector at the 3' end of the D capsid protein gene, which produced highly complex repertoires (1x10(8) and 2x10(7) phage). These libraries were affinity selected with a monoclonal antibody against the neural specific factor GAP-43 and with polyclonal antibodies that recognize the EMX1 and EMX2 homeoproteins. In both cases rapid identification of specific clones was achieved, which demonstrates the great potential of the lambda display system for generating affinity selectable cDNA libraries from complex genomes.

Mutations of Gly to Ala in human glutathione transferase P1-1 affect helix 2 (G-site) and induce positive cooperativity in the binding of glutathione.

Previous kinetic studies on human glutathione transferase P1-1 have indicated that the motions of an irregular alpha-helix (helix 2) lining the glutathione (GSH) binding site are viscosity dependent and may modulate the affinity of GSH binding. The effect of single amino acid residue substitutions (Gly to Ala) in this region is investigated here by site-directed mutagenesis. Three mutants (Gly41Ala, Gly50Ala and Gly41Ala/Gly50Ala) were overexpressed in Escherichia coli, purified, and characterized by kinetic, structural, and spectroscopic studies. All these mutant enzymes show kcat values similar to that of the wild-type enzyme, while the [S]0.5 for GSH increases about eight-fold in the Gly41Ala mutant and more than 100-fold in the Gly41Ala/Gly50Ala double mutant. This change in affinity towards GSH is accompanied by an induced positive cooperativity as reflected by Hill coefficients of 1.4 (Gly41Ala) and 1.7 (Gly41Ala/Gly50Ala) upon substrate binding. Taken together, these data suggest that the region around helix 2 is markedly altered leading to the observed intersubunit communication. Molecular modeling of the Gly41Ala/Gly50Ala mutant and of the inactive oxidized form of the native enzyme provides a structural explanation of our results.

Comparison of total and partial traumatic tears of the subscapularis tendon.

We treated surgically 16 shoulders with an isolated traumatic rupture of the subscapularis tendon over a six-year period. Nine patients had a total and seven a partial tear of the subscapularis tendon. Repair was undertaken through a small deltopectoral groove approach. The mean Constant score improved in total tears from 38.7 to 89.3 points (p = 0.003) and in partial tears from 50.7 to 87.9 points (p = 0.008). The total tears were significantly more improved by surgery than the partial tears (p = 0.001). The delay between trauma and surgery was inversely proportional to the improvement in the Constant score suggesting that early diagnosis and surgical repair improves outcome.

An experimental canine model for subchondral lesions of the knee joint.

Aim of the study was to create an animal model for the investigation of the role of subchondral bone damage without initial cartilage lesion in the pathogenesis of osteoarthritis, the mechanical properties of the joints as well as its role in cartilage metabolism. Therefore, after cadaver studies an animal model was created to apply a transarticular load to the femoro-patellar joint under reproducible conditions and produce a pure subchondral damage without affecting the articular cartilage. Following the cadaver studies a first group of four dogs was impacted to identify forces to produce isolated subchondral fractures in the femoral condyle. Then a second group of 12 dogs knee joints was impacted under identical conditions with forces of approximately 2100 N to produce similar subchondral fractures without cartilage damage in one joint under MRI control: T1-weighted SE-sequences. T2-weighted TSE, fat suppressed TIRM-sequences and 3D-FLASH fat saturated sequences. FLASH 3D-sequences revealed intact cartilage after impact in all cases and TIRM-sequences showed subchondral fractures representing bleeding, microfractures and fragmented bone trabecules. Turbo spin echo sequences and T1-weighted images revealed other intact intraarticular structures such as ligaments and menisci. The proposed experimental animal model is suitable to investigate the effect of pure subchondral damage on the articular cartilage and on means of treatment of cartilage defects without surgical intervention and without initial cartilage damage.

Mimotopes of the hyper variable region 1 of the hepatitis C virus induce cross-reactive antibodies directed against discontinuous epitopes.

Hepatitis C virus (HCV) is a major cause worldwide of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma, and the development of an effective vaccine represents a high priority goal. The hyper variable region 1 (HVR1) of the second envelope protein (E2) of HCV contains a principal neutralizing determinant, but it is highly variable among different isolates and it is involved in the escape from host immune response. To be effective, a vaccine should elicit a cross-reacting humoral response against the majority of viral variants. We show that it is possible to achieve a broadly cross-reactive immune response in rabbits by immunization with mimotopes of the HVR1, selected from a specialized phage library using HCV patients' sera. Some of the cross-reacting anti-mimotope antibodies elicited in rabbits, recognize discontinuous epitopes in a manner similar to those induced by the virus in infected patients.

The Rhizobium leguminosarum biovar phaseoli glnT gene, encoding glutamine synthetase III.

Plasmid pGE203 contains the Rhizobium leguminosarum biovar phaseoli glnT locus. Glutamine synthetase III (GSIII) was purified from a glutamine auxotrophic strain of Klebsiella pneumoniae carrying this plasmid. Sequencing of a 2.4-kb fragment containing the glnT locus reveals an open reading frame of 435 amino acids (aa), whose first eight aa are identical to those determined from pure GSIII by direct aa sequencing, thus confirming that glnT indeed codes for GSIII activity. The comparison of the GSIII aa sequence with the reported sequence of GSs from other organisms shows a significant degree of homology. Since the three-dimensional structure of GS from Salmonella typhimurium is known, a three-dimensional model of GSIII was built by homology.

Hepatitis C virus proteins as targets for drug development: the role of bioinformatics and modelling.

Hepatitis C virus (HCV), a member of the Flaviviridae family, has been recognised to be responsible for both parenterally transmitted and sporadic non-A and non-B hepatitis affecting 1-3% of the world population. HCV is a positive stranded RNA virus encoding a single polyprotein which contains at least ten unique structural and non-structural proteins. Amongst these the structural protein E2 has been of special interest for vaccine development and the serine protease NS3, which is responsible for cleavage of the polyprotein, for the development of small molecule inhibitors. We will focus on the contribution of computational techniques and the use of structural information for the design and discovery of novel therapeutic agents for these targets. Both drug discovery and vaccine design efforts will be discussed taking into account also the problem of emerging resistance.

Induction of cross-reactive humoral immune response by immunization with mimotopes of the hypervariable region 1 of the hepatitis C virus.

Hepatitis C Virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma, worldwide, and the development of an effective vaccine represents a high priority goal. The Hyper Variable Region 1 (HVR1) of the second Envelope protein (E2) of HCV contains a principal neutralizing determinant, but it is highly variable among different isolates and it is involved in the escape from host immune response. Thus, to be effective, a vaccine should elicit a cross-reacting humoral response against the majority of viral variants. We show that it is possible to achieve a broadly cross-reactive immune response in rabbits by immunization with mimotopes of the HVR1. selected from a specialized phage library using HCV patients' sera. At least some of the cross-reacting anti-mimotope antibodies, elicited in rabbits, recognize discontinuous epitopes in a manner similar to those induced by the virus in infected patients.

[Arthroscopic therapy of osteochondrosis dissecans of the talus--follow-up with a new "Ankle Score"]. / Arthroskopische Therapie der Osteochondrosis dissecans des Talus--Nachuntersuchung mit einem neuen "Ankle Score".

INTRODUCTION: Since the advent of operative ankle arthroscopy specific treatment of osteochondritis dissecans of the talus underwent rapid progress. Besides optimizing well-known methods as drilling, spongeous plastic, curettage or refixation of dissecates new trends go to transplantation of cultivated cartilage and osteochondral allografts. Previous follow-up examinations suffer on the one hand from partially small numbers of cases, on the other hand comparisons are difficult because so far no rating system of the function of the upper ankle does exist. MATERIAL AND METHODS: Within three years 34 patients underwent arthroscopic treatment of osteochondritis dissecans of the talus, 16 with percutaneous drilling, 12 spongeous plastics, three refixations and three curettages. The average age of the 22 men and 12 women was 25 years (11-48 years). A newly developed score system and a follow up MRI was used in a follow-up of 29 of the patients. Up to 100 points are given in the categories pain, stability/insecurity, efficiency/painfree walking distance, gait, differences in circumference, motility and power. RESULTS: 27 of the 34 patients had a trauma history. 20 lesions were localized at the lateral talus, they all had a trauma history. In 7 of the 14 lesions at the medial part of the talus there was no evidence of trauma. The 29 patients in the follow-up achieved an average of 87 points, the 16 patients after K-wire drilling 85 points and the 12 patients after spongeous plastic 90 points. Deductions were noted likewise in the subjective and objective parameters. 100 points were reached by 4 patients. DISCUSSION: Cultured chondrozytes and osteochondral grafts are new trends in treatment of osteochondritis dissecans while arthroscopically controlled spongeous plastic after curettage and K-wire drilling represent the main component of early stages with intact or partially fractured cartilage surface. Results of K-wire drilling are negligible worse than those of spongeous plastic, which is attributed to a generous perforation of the sclerosis. This is contributed to an improved preoperative diagnosis with MRI.