The Incidence and Clinical Relevance of Graft Hypertrophy After Matrix-Based Autologous Chondrocyte Implantation

Background: Graft hypertrophy is the most common complication of periosteal autologous chondrocyte implantation (p-ACI). Purpose: The aim of this prospective study was to analyze the development, the incidence rate, and the persistence of graft hypertrophy after matrix-based autologous chondrocyte implantation (mb-ACI) in the knee joint within a 2-year postoperative course. Study Design: Case series; Level of evidence, 4. Methods: Between 2004 and 2007, a total of 41 patients with 44 isolated cartilage defects of the knee were treated with the mb-ACI technique. The mean age of the patients was 35.8 years (standard deviation [SD], 11.3 years), and the mean body mass index was 25.9 (SD, 4.2; range, 19-35.3). The cartilage defects were arthroscopically classified as Outerbridge grades III and IV. The mean area of the cartilage defect measured 6.14 cm2 (SD, 2.3 cm2). Postoperative clinical and magnetic resonance imaging (MRI) examinations were conducted at 3, 6, 12, and 24 months to analyze the incidence and course of the graft. Results: Graft hypertrophy developed in 25% of the patients treated with mb-ACI within a postoperative course of 1 year; 16% of the patients developed hypertrophy grade 2, and 9% developed hypertrophy grade 1. Graft hypertrophy occurred primarily in the first 12 months and regressed in most cases within 2 years. The International Knee Documentation Committee (IKDC) and visual analog scale (VAS) scores improved during the postoperative follow-up time of 2 years. There was no difference between the clinical results regarding the IKDC and VAS pain scores and the presence of graft hypertrophy. Conclusion: The mb-ACI technique does not lead to graft hypertrophy requiring treatment as opposed to classic p-ACI. The frequency of occurrence of graft hypertrophy after p-ACI and mb-ACI is comparable. Graft hypertrophy can be considered as a temporary excessive growth of regenerative cartilage tissue rather than a true graft hypertrophy. It is therefore usually not a persistent or systematic complication in the treatment of circumscribed cartilage defects with mb-ACI

On the direction of transcription of cloned genes in Neurospora crassa.

On the direction of transcription of cloned genes in Neurospora crassa

Co-regulation of two tandem genes by one blue-light element in Neurospora crassa

Many genes of Neurospora crassa are regulated by blue light: al-1 (Schmidhauser et al. 1990 Mol. Cell. Biol. 10:5064-5070), al-2 (Lauter, Schmidhauser, Yanofsky, Russo unpublished), al-3 (Nelson et al. 1989 Mol. Cell. Biol. 9:1271-1276), bli-3, bli-4, bli-7, bli-13 (Sommer et al. 1989 NAR 17:5713-5723). For none of these genes are the blue light cis-regulatory sequences (blue-light elements, BE) known. Here we report the presence of such BE in front of bli-4

Effect of the defect localization and size on the success of third-generation autologous chondrocyte implantation in the knee joint

Introduction. Femoral and patellar cartilage defects with a defect size > 2.5 cm2 are a potential indication for an autologous chondrocyte implantation (ACI). However, the influence of the localization and the absolute and relative defect size on the clinical outcome has not yet been determined. The purpose of this study is to analyze the influence of the localization and the absolute and relative defect size on the clinical outcome after third-generation autologous chondrocyte implantation. Methods. A total of 50 patients with cartilage defects of the knee were treated with third-generation autologous chondrocyte implantation (Novocart® 3D). A match paired analysis was performed of 25 treated femoral and 25 treated patella defects with a follow-up of three years. MRI data was used to do the manual segmentation of the cartilage layer throughout the knee joint. The defect size was determined by taking the defect size measured in the MRI in relation to the whole cartilage area. The clinical outcome was measured by the IKDC score and VAS pre-operatively and after six, 12, 24, and 36 months post-operatively. Results. IKDC and VAS scores showed a significant improvement from the baseline in both groups. Femoral cartilage defects showed significantly superior clinical results in the analyzed scores compared to patellar defects. The femoral group improved IKDC from 33.9 (SD 18.1) pre-operatively to 71.5 (SD 17.4) after three years and the VAS from 6.9 (SD 2.9) pre-operatively to 2.4 (SD 2.5) after three years. In the patellar group, IKDC improved from 36.1 (SD 12.6) pre-operatively to 54.7 (SD 20.3) after three years and the VAS improved from 6.7 (SD 2.8) pre-operatively to 3.4 (SD 2.) after three years. Regarding the defect size, results showed that the same absolute defect size at med FC (4.8, range 2–15) and patella (4.6, range 2–12) has a significantly different share of the total cartilaginous size of the joint compartment (med FC: 6.7, range 1.2–13.9; pat: 18.9, range 4.0–47.0). However, there was no significant influence of the relative defect size on the clinical outcome in either patellar or femoral localization. Conclusion. Third-generation autologous chondrocyte implantation in ACI-treated femoral cartilage defects leads to a superior clinical outcome in a follow-up of three years compared with patellar defects. No significant influence of the defect size was found in either femoral or patellar cartilage defects

Increase in the Tibial Slope Reduces Wear after Medial Unicompartmental Fixed-Bearing Arthroplasty of the Knee

Introduction. Unicompartmental arthroplasty of the knee in patients with isolated medial osteoarthritis gives good results, but survival is inferior to that of total knee prosthesis. Knees may fail because positioning of the prosthesis has been suboptimal. The aim of this study was to investigate the influence of the tibial slope on the rate of wear of amedial fixed-bearing unicompartmental knee arthroplasty. Materials and Methods. We simulated wear on a medial fixed-bearing unicompartmental knee prosthesis (Univation) in vitro with a customised, four-station, and servohydraulic knee wear simulator, which exactly reproduced the walking cycle (International Organisation for Standardisation (ISO) 14243-1: 2002(E)). The medial prostheses were inserted with 3 different posterior tibial slopes: 0 degrees, 4 degrees, and 8 degrees (n = 3 in each group). Results. The wear rate decreased significantly between 0 degrees and 4 degrees slope from 10.4 (SD 0.62) mg/million cycles to 3.22 (SD 1.71) mg/million cycles. Increasing the tibial slope to 8 degrees did not significantly change the wear rate. Discussion. As an increase in the tibial slope reduced the wear rate in a fixed-bearing prosthesis, a higher tibial slope should be recommended. However, other factors that are influenced by the tibial slope (e.g.,the tension of the ligament) must also be considered

Increase in the Tibial Slope Reduces Wear after Medial Unicompartmental Fixed-Bearing Arthroplasty of the Knee

Introduction. Unicompartmental arthroplasty of the knee in patients with isolated medial osteoarthritis gives good results, but survival is inferior to that of total knee prosthesis. Knees may fail because positioning of the prosthesis has been suboptimal. The aim of this study was to investigate the influence of the tibial slope on the rate of wear of amedial fixed-bearing unicompartmental knee arthroplasty. Materials and Methods. We simulated wear on a medial fixed-bearing unicompartmental knee prosthesis (Univation) in vitro with a customised, four-station, and servohydraulic knee wear simulator, which exactly reproduced the walking cycle (International Organisation for Standardisation (ISO) 14243-1: 2002(E)). The medial prostheses were inserted with 3 different posterior tibial slopes: 0 degrees, 4 degrees, and 8 degrees (n = 3 in each group). Results. The wear rate decreased significantly between 0 degrees and 4 degrees slope from 10.4 (SD 0.62) mg/million cycles to 3.22 (SD 1.71) mg/million cycles. Increasing the tibial slope to 8 degrees did not significantly change the wear rate. Discussion. As an increase in the tibial slope reduced the wear rate in a fixed-bearing prosthesis, a higher tibial slope should be recommended. However, other factors that are influenced by the tibial slope (e.g.,the tension of the ligament) must also be considered

Graft Hypertrophy After Third-Generation Autologous Chondrocyte Implantation Has No Correlation With Reduced Cartilage Quality: Matched-Pair Analysis Using T2-Weighted Mapping

Background: Graft hypertrophy is common after matrix-based autologous chondrocyte implantation (ACI) in the knee joint. However, it is not clear whether graft hypertrophy is a complication or an adjustment reaction in the cartilage regeneration after ACI. Purpose: To analyze the cartilage quality of the ACI regeneration with graft hypertrophy using T2-weighted mapping. Study Design: Cohort study;Level of evidence, 2. Methods: A total of 91 patients with isolated cartilage defects (International Cartilage Repair Society [ICRS] grade III-IV) of the knee were treated with Novocart 3D, a third-generation, matrix-based, ACI procedure in the knee joint. All patients were evaluated with a standardized magnetic resonance imaging protocol after 3, 6, 12, 24, 36, and 48 months postoperatively. For morphological and biochemical assessment, the T2-weighted relaxation times of the ACI grafts as well as the healthy surrounding cartilage were determined. The results of the 20 patients with graft hypertrophy (hypertrophic group) were compared with the results of 21 matched patients without graft hypertrophy (nonhypertrophic group) after ACI. Match-paired analysis was performed by comparison of age, defect size, and body mass index. Results: The T2-weighted relaxation times of the ACI graft showed significant improvement, with values decreasing from 52.1 milliseconds to 33.3 milliseconds after 48 months. After 12 months, the T2-weighted relaxation times were constant and comparable with the healthy surrounding cartilage. Graft hypertrophy was seen in 22% (n = 20) of the patients who underwent ACI. A significant difference in T2-weighted relaxation times between the hypertrophic and nonhypertrophic ACI grafts could not be found except after 36 months (hypertrophic T2-weighted relaxation time/nonhypertrophic T2-weighted relaxation time: 3 months, 48.0/56.4 ms, P = .666;6 months, 45.6/42.5 ms, P = .280;12 months, 39.3/34.7 ms, P = .850;24 months, 34.8/32.2 ms, P =.742;36 months, 34.6/38.2 ms, P = .030;48 months, 34.2/32.3 ms, P = .693). Conclusion: The T2-weighted relaxation time of the ACI graft cartilage showed significant improvements over the observation period of 4 years postoperatively. After 2 years, graft maturation was completed. Graft hypertrophy after ACI was seen in 22% of the patients. Reduced cartilage quality could not be found in patients with graft hypertrophy after ACI

Renormalization of the QED of second order spin 1/2 fermions

In this work we study the renormalization of the electrodynamics of spin 1/2 fermions in the Poincar\'e projector formalism which is second order in the derivatives of the fields. We analyze the superficial degree of divergence of the vertex functions of this theory, calculate at one-loop level the vacuum polarization, fermion self-energy and \gamma-fermion-fermion vertex function and the divergent piece of the one-loop contributions to the \gamma-\gamma-fermion-fermion vertex function. It is shown that these functions are renormalizable independently of the value of the gyromagnetic factor g which is a free parameter of the theory. We find a photon propagator and a running coupling constant \alpha (q^2) that depend on the value of g. The magnetic moment form factor contains a divergence associated to g which disappears for g=2 but in general requires the coupling g to be renormalized. A suitable choice of the renormalization condition for the magnetic form factor yields the one loop finite correction \Delta{g}=g\alpha/2\pi. For a particle with g=2 we recover results of Dirac theory for the photon propagator, the running of \alpha (q^2) and the one-loop corrections to the gyromagnetic factor.Comment: 20 pages including 6 figures. Rewritten paper, results unchanged, version accepted in PRD. Results written in terms of Passarino-Veltman scalar integral

Chiral corrections to the vector and axial couplings of quarks and baryons

We calculate chiral corrections to the semileptonic vector and axial quark coupling constants using a manifestly Lorentz covariant chiral quark approach up to order O(p4) in the two- and tree-flavor picture. These couplings are then used in the evaluation of the corresponding couplings which govern the semileptonic transitions between octet baryon states. In the calculation of baryon matrix elements we use a general ansatz for the spatial form of the quark wave function, without referring to a specific realization of hadronization and confinement of quarks in baryons. Matching the physical amplitudes calculated within our approach to the model-independent predictions of baryon chiral perturbation theory (ChPT) allows one to deduce the connection between our parameters and those of baryon ChPT.Comment: 28 pages, 4 figure

Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia

Immune-mediated haemolytic anaemia (IMHA) is reported to be the most common autoimmune disease of dogs, resulting in significant morbidity and mortality in affected animals. Haemolysis is caused by the action of autoantibodies, but the immunological changes that result in their production have not been elucidated.To investigate the frequency of regulatory T cells (Tregs) and other lymphocyte subsets and to measure serum concentrations of cytokines and peripheral blood mononuclear cell expression of cytokine genes in dogs with IMHA, healthy dogs and dogs with inflammatory diseases.19 dogs with primary IMHA, 22 dogs with inflammatory diseases and 32 healthy control dogs.Residual EDTA-anti-coagulated blood samples were stained with fluorophore-conjugated monoclonal antibodies and analysed by flow cytometry to identify Tregs and other lymphocyte subsets. Total RNA was also extracted from peripheral blood mononuclear cells to investigate cytokine gene expression, and concentrations of serum cytokines (interleukins 2, 6 10, CXCL-8 and tumour necrosis factor α) were measured using enhanced chemiluminescent assays. Principal component analysis was used to investigate latent variables that might explain variability in the entire dataset.There was no difference in the frequency or absolute numbers of Tregs among groups, nor in the proportions of other lymphocyte subsets. The concentrations of pro-inflammatory cytokines were greater in dogs with IMHA compared to healthy controls, but the concentration of IL-10 and the expression of cytokine genes did not differ between groups. Principal component analysis identified four components that explained the majority of the variability in the dataset, which seemed to correspond to different aspects of the immune response.The immunophenotype of dogs with IMHA differed from that of dogs with inflammatory diseases and from healthy control dogs; some of these changes could suggest abnormalities in peripheral tolerance that permit development of autoimmune disease. The frequency of Tregs did not differ between groups, suggesting that deficiency in the number of these cells is not responsible for development of IMHA