Articular cartilage repair

The net and basic reproduction numbers are among the most widely-applied concepts in infectious disease epidemiology. A net reproduction number (the average number of secondary infectious cases resulting from each case in a given population) of above 1 is conventionally associated with an increase in incidence; the basic reproduction number (defined analogously for a 'totally susceptible' population) provides a standard measure of the 'transmission potential' of an infection. Using a model of the epidemiology of tuberculosis in England and Wales since 1900, we demonstrate that these measures are difficult to apply if disease can follow reinfection, and that they lose their conventional interpretations if important epidemiological parameters, such as the rate of contact between individuals, change over the time interval between successive cases in a chain of transmission (the serial interval). The net reproduction number for tuberculosis in England and Wales appears to have been approximately 1 from 1900 until 1950, despite concurrent declines in morbidity and mortality rates, and it declined rapidly in the second half of this century. The basic reproduction number declined from about 3 in 1900, reached 2 by 1950, and first fell below 1 in about 1960. Reductions in effective contact between individuals over this period, measured in terms of the average number of individuals to whom each case could transmit the infection, meant that the conventional basic reproduction number measure (which does not consider subsequent changes in epidemiological parameters) for a given year failed to reflect the 'actual transmission potential' of the infection. This latter property is better described by a variant of the conventional measure which takes secular trends in contact into account. These results are relevant for the interpretation of trends in any infectious disease for which epidemiological parameters change over time periods comparable to the infectious period, incubation period or serial interval.     

Articular cartilage lesions of the knee

We have evaluated the role of various protein kinases on the induction of the gadd (growth arrest and DNA damage inducible) genes, using a panel of protein kinase inhibitors. Our data indicate that three different stress response pathways mediating gadd gene induction are most likely regulated by different protein kinases or combinations of protein kinases. The protein kinase inhibitor staurosporine and the temperature sensitive (ts) p34cdc2 mutant reduced induction by the alkylating agent methylmethane sulfonate (MMS) of the rodent gadd45 and gadd153 genes. However, staurosporine had no effect of the ionizing radiation (IR) induction of the human GADD45. Caffeine and 2-aminopurine, on the other hand, completely blocked this IR induction. Suramin, an antitumor drug that interferes with the interaction of growth factors with their receptors, inhibited the UV radiation induction of GADD45 and GADD153 but had no effect on the MMS and IR pathways. Elevated expression of gadd45 by medium depletion (starvation) was partially reduced by the addition of either genistein or tyrphostin, two protein tyrosine kinase inhibitors, while gadd153 was affected by tyrphostin only. Two inhibitors acting preferentially on cAMP-dependent protein kinase (PKA), N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide, HCl (H8) and protein kinase inhibitor (PKI), also had a moderate effect on the medium depletion-induced levels of both gadd genes. Thus, these varied effects of inhibitors on gadd gene responses point to important differences in the pathways controlling these responses.     

Articular cartilage volume in the knee: semiautomated determination from three-dimensional reformations of MR images

PURPOSE: To determine the accuracy of semiautomated quantification of articular cartilage volume from three-dimensional (3D) reformations of magnetic resonance (MR) images. MATERIALS AND METHODS: Sagittal, fat-suppressed, 3D, spoiled gradient-recalled-echo MR imaging of two bovine and two human cadaver knees was performed. Articular cartilage volume was calculated from 3D reformations of the MR images by using a semiautomated program written at the authors' institution. Calculated volumes were compared with directly measured volumes of the surgically removed articular cartilage. RESULTS: The percentage of error of the MR imaging-determined volumes was 6.53% +/- 4.75 (mean +/- standard deviation). A strong correlation between the two sets of observations was shown (r=.997). Linear regression showed the calculated volumes to be highly accurate (slope=1.002, P>.25). Repeated reformations yielded volumes that were reproducible (mean absolute error, 0.013 mL +/- 0.019) and not significantly different from the measured volume (P>.10). CONCLUSION: Semiautomated quantification of knee articular cartilage from MR images yields highly accurate cartilage volumes.     

Treatment of deep cartilage defects of the patella with periosteal transplantation

Injuries of the nasoethmoid-orbital (NEO) region are associated with midfacial fractures or fractures of the frontobase in over 90% of all cases. In up to 70% fractures of the skull base run through the roof of the ethmoidal bone or the lamina cribrosa. There are different surgical approaches for the treatment of these complex fractures. Between 1990 and 1997 50 patients with midfacial fractures in association with NEO fractures were treated in the Klinik für Mund-, Kiefer- und Gesichtschirurgie, Kantonsspital Luzern, Switzerland. Of these, 25 had suffered midfacial fractures combined with fractures of the nasoethmoid-orbital and frontobasal region and were treated via a transcranial approach. The other 25 patients with midfacial and NEO fractures without involvement of the frontobasis were managed by subcranial incisions. A total of 47 patients were followed up for up to 4 years. The results were reevaluated retrospectively. There was no case of secondary liquorrhea, intracranial or ethmoidal infection. Our therapeutic concept of transcranial and subcranial management of NEO fractures in combination with frontobasal and midfacial fractures is demonstrated.     

Articular cartilage in the knee: mapping of the physiologic parameters at MR imaging with a local gradient coil--preliminary results

The authors designed and constructed a local gradient coil that produces large gradients and short rise times and connects to their clinical system. In a cadaveric patellar cartilage specimen, the coil was used to acquire images of the physiologic parameters T1, T2, proton density, and apparent diffusion coefficient. Variations in these parameters were evident in regions of normal and abnormal cartilage.     

Articular cartilage superficial zone protein (SZP) is homologous to megakaryocyte stimulating factor precursor and Is a multifunctional proteoglycan with potential growth-promoting, cytoprotective, and lubricating properties in cartilage metabolism

We have performed cDNA sequencing and homology analyses to elucidate the complete amino acid composition for a superficial zone protein (SZP) from human and bovine cartilage which has previously been shown to be a proteoglycan specifically synthesized by chondrocytes located at the surface of bovine articular cartilage and also some synovial lining cells. The results of this study indicate that cartilage SZP is homologous with a glycoprotein first described as the precursor protein of a megakaryocyte stimulating factor (MSF). Sequence comparisons and analyses indicate that (i) the amino acid composition of SZP is highly conserved between bovine and human species, (ii) SZP contains structural motifs at the N- and C-termini which are similar to those found in vitronectin and which may impart cell-proliferative and matrix-binding properties to the molecule, and (iii) SZP contains large and small mucin-like repeat domains composed of the sequences KEPAPTTT/P (76-78 repeats) and XXTTTX (6-8 repeats), respectively, which occur within a large central region of approximately 940 amino acids. The mucin-like domains are likely to be substituted with O-linked oligosaccharides which would impart lubricating properties to SZP which in part accumulates at the articular cartilage-synovial fluid interface. Additionally, we have shown that interleukin-1 inhibits the biosynthesis of chondrocyte SZP, while TGF-beta and IGF-1 increase its biosynthesis, and that in pathological (osteoarthritic) human articular cartilage SZP mRNA can be expressed as an alternatively spliced variant lacking exons 4 and 5 which encode a potential heparin binding domain. The occurrence of different SZP alternative splice variants and the differential expression of SZP in the presence of cytokines and growth factors suggest that SZP may play an important cytoprotective role by preventing cellular adhesion to the articular cartilage surface in normal cartilage metabolism. Modifications to the structure of SZP, coupled with inhibition of SZP synthesis during inflammation, may account for the attachment and invasion of pannus observed in inflammatory joint diseases.     

人工软骨材料—聚乙烯醇水凝胶的研制

聚乙烯醇溶液经反复冷冻-融化、真空脱水及辐照交联处理后,制得一种人工软骨材料PVA-水凝胶.通过光学显微镜和扫描电镜观察PVA-水凝胶的微观形貌;通过差示扫描量热法(DSC)及相应的力学性能试验研究反复冷冻-融化、真空脱水和辐照交联对PVA-水凝胶结晶和力学性能的影响.该PVA-水凝胶的力学性能与人关节软骨相近,可望用于人工软骨材料.     

人工软骨材料摩擦学特性

为了改善自行人工关节的润滑性能,需采用全新的结构设计,研制具有良好润滑性能的低弹性模量材料.用自行研制的振子式磨擦仪观测了生物相容性较好的3种聚合物材料,即硅橡胶、聚氨酯、聚乙烯醇水凝胶(PVA-H)的摩擦因数和润滑制度.试验结果表明:有润滑时,硅橡胶和聚氨酯分别与316L不锈钢组成的摩擦副,其润滑制度是边界润滑,而聚乙烯醇水凝胶(PVA-H)/316L不锈钢摩擦副的润滑制度为混合润滑.     

透明质酸对人工关节材料的润滑作用

配合人工软骨材料的研究,探讨透明质酸(HA)作为摩擦副的人工滑液时的润滑性能.在PVA-H/316L,PVA-H/PVA-H两类摩擦副上,利用锥板式粘度计、改进后的振子式摩擦仪和M2000型磨损试验机,测定了不同质量分数的HA溶液的流变性质、摩擦性能和磨损性能.结果表明,HA溶液一定程度上具有天然滑液的流变性质,并有效地降低了摩擦副的摩擦磨损,其对PVA-H/PVA-H摩擦副润滑作用更佳,且0.75%(质量分数)的HA溶液表现出优于体积分数为30%小牛血清的润滑性能,可认为HA是很有前途的人工滑液.     

Poroviscoelastic Two-Dimensional Anisotropic Solution with Application to Articular Cartilage Testing

The transverse anisotropic poromechanics solution for the two-dimensional Mandel-type problem geometry is extended in this paper to account for the orthotropic nature of the porous media, thus mimicking the response of articular cartilage samples when subjected to load perturbation. The anisotropic solution presented takes into account the viscoelastic and anisotropic nature of the fluid-saturated cartilage specimen sandwiched between two impermeable rigid plates and subjected to quasi-static step loading conditions; thus simulating the unconfined compressive test responses of cartilage samples in biomechanics laboratory setups. The solution addresses the stress, fluid pressure, and displacement results due to load application through exact modeling of the intrinsic nature of the orthotropic viscoelastic matrix structure as well as the compressible interstitial fluid flow responses. Poromechanical parameter characterization and modeling of biological tissues, such as cartilage, will find this analytical solution to the two-dimensional anisotropic poroviscoelastic geometry very useful. This problem will not only serve as a benchmark for validating numerical schemes and simulations but also assist in calibrating laboratory results on biological tissues, including cyclic loadings.     

Articular and tendon manifestations indicating the stage of rheumatoid polyarthritis

Synovial inflammation and the destruction which results from recurrent and chronic inflammation lead to arthritis and tenosynovitis. Clinical manifestations are bilateral and symmetrical, affecting virtually all joints. The hands and the feet are the main targets. Cervical involvement should be routinely investigated. X-rays demonstrate the erosion and deformation caused by rheumatoid arthritis. Altogether, the manifestations of the disease constitute a distinct and painful handicap. Treatment should be undertaken as early as possible in the course of rheumatoid arthritis in an attempt to avoid evolution toward irreversible destruction.     

MRI and articular cartilage

There are considerable laboratory data and information from animal and continuous culture in vitro models to support continuous infusion therapy for penicillins and cephalosporins, but, as yet, the only existing clinical data relate to cephalosporins. Penicillins do not exert concentration-dependent killing in the therapeutic range but have a post-antibiotic effect (PAE) against Gram-positive cocci but not Gram-negative rods. Animal models indicate the time (T) during which the serum concentrations exceed the minimum inhibitory concentration (MIC) of the pathogen [T > MIC] determines outcomes. Pharmacokinetic studies in humans indicate that continuous infusion with penicillins is possible but there are no clinical data on efficacy. Cephalosporins have similar pharmacodynamic properties to penicillins; T > MIC determines outcome. Data related to ceftazidime indicate that the drug concentration at steady-state (Css) should exceed the pathogen MIC by > 1-fold and perhaps by 4- to 5-fold or more. Human pharmacokinetics of ceftazidime administered by continuous infusion to a wide variety of patient groups indicates that Css of > 20 mg/L can easily be achieved using conventional daily doses. Clinical data indicate increased effectiveness of a continuous regimen in neutropenic patients with Gram-negative infection. Furthermore cefuroxime administration by continuous infusion has resulted in lower doses and shorter course durations. Little is known of the pharmacodynamics of monobactams and there are few clinical data on continuous infusion therapy. Carbapenems have different pharmacodynamics to other beta-lactams as they have concentration-dependent killing and a PAE with both Gram-positive and Gram-negative bacteria. While T > MIC has a role in determining outcomes, the proportion of the dosing interval for which serum drug concentrations should exceed the pathogen MIC is less than for other beta-lactams. In vitro models have shown that continuous infusion is effective, as is less frequent dosing. There are few data on continuous infusion of carbapenems but some patients have been treated with once-daily dosing. Clinically, continuous infusion therapy with penicillins and cephalosporins should be considered in patients infected with susceptible Gram-negative rods not responding to conventional therapy. As an approximation, the same total daily dose should be given but a bolus intravenous injection should be give at the start of continuous infusion to ensure Css is reached rapidly. The Css may be difficult to predict and determination of serum drug concentrations may be indicated. Ideally, the Css should be calculated based on the MIC of the potential pathogen and may be higher or lower than the Css achieved by a conventional daily dose.     

Reaction of hypochlorous acid with bovine nasal cartilage comparison to pig articular cartilage

The action of sodium hypochlorite (NaOCl) on bovine nasal cartilage was studied by proton nuclear magnetic resonance (1H-NMR) spectroscopy in order to model degradation processes of cartilage caused by neutrophil-derived hypochlorous acid. Nasal cartilage was chosen as a mean of comparison because it differs from articular cartilage in its composition. It contains some more proteoglycans, i.e. polymeric carbohydrates and less collagen than articular cartilage. This is important for studying the influence of hypochlorous acid on cartilage components (collagen and polysaccharides). Cartilage samples were incubated at 37 degrees C with phosphate buffer in the presence or absence of NaOCl. Supernatants were collected and assayed by NMR-spectroscopy. In the presence of pure phosphate buffer, the supernatants of bovine nasal cartilage were less rich in low molecular mass metabolites (e.g. amino acids, lactate) than articular cartilage. However, intense signals for highly mobile N acetyl groups of cartilage polysaccharides were detectable in nasal cartilage. NaOCl caused an increase in signals for acetate and formiate. Signals for N-acetyl groups rose only during the first 25 minutes of incubation with NaOCl. Then, their concentration decreased markedly. These changes were related to an enhanced release of chondroitinsulfate from nasal cartilage.     

Integrated Model of IGF-I Mediated Biosynthesis in a Deformed Articular Cartilage

Maintenance of articular cartilage’s functional mechanical properties ultimately depends on the balance between the extracellular matrix component biosynthesis, degradation, and loss. A variety of factors are known to modulate the rate of cartilage matrix synthesis (e.g., growth factors and stress/strain environment). In the present study, we develop an integrated mathematical model that quantifies biological processes within cartilage tissue modulated by insulin-like growth factors (IGFs). Specifically, the model includes IGF transport through a deforming porous media, competitive binding to binding proteins and cell receptors, and matrix macromolecule biosynthesis—particularly glycosaminoglycans (GAGs). These newly synthesized matrix molecules are then able to modify the material properties of cartilage. The model is used to investigate the effect of synovial fluid IGF-I concentration on cartilage homeostasis. The results presented here suggest that GAG production can be rapidly “switched on” when the concentration of IGF-I reaches a certain threshold, while it is predicted that high receptor concentration leads to heterogeneous matrix production. As for the combined effect of IGF-I and mechanical loading on biosynthesis, the current model predicts that a loading regime with high strain magnitude (e.g., 10%) can achieve a synergistic effect on matrix protein production. Furthermore, dynamic loading is seen to promote spatial homogeneous GAG production.     

Articular interposition of trochanteric wires in a failed total hip replacement

This is a case report of a previously unrecorded complication of trochanteric osteomy in a total hip arthroplasty. The trochanteric wire fixation failed and wire fragments migrated from the osteotomy site into the joint space. Revision total arthroplasty was elected. An additional potential complication of trochanteric osteotomy is noted.