Wear-lines and split-lines of human patellar cartilage: relation to tensile biomechanical properties.

BACKGROUND: Articular cartilage undergoes age-associated degeneration, resulting in both structural and functional biomechanical changes. At early stages of degeneration, wear-lines develop in the general direction of joint movement. With aging, cartilage exhibits a decrease in tensile modulus. The tensile modulus of cartilage has also been related to the orientation of the collagen network, as revealed by split-lines. OBJECTIVE: To determine the relative contribution of wear-line and split-line orientation on the tensile biomechanical properties of human patellar cartilage from different depths. METHODS: In human patellar cartilage, wear- and split-lines are aligned parallel to each other at the proximal facet, and perpendicular to each other at the medial facet. Using superficial, middle, and deep cartilage sections from these two sites, tensile samples were prepared in two orthogonal orientations. Thus, for each depth, there were four groups of samples, with their long axes were aligned either parallel or perpendicular to wear-line direction and also aligned parallel or perpendicular to split-line direction. Uniaxial tensile tests were performed to assess equilibrium and ramp moduli. RESULTS: Tensile equilibrium moduli varied with wear-line orientation (P<0.05) and depth (P<0.001), in an interactive manner (P<0.05), and tended to vary with split-line orientation (P=0.16). In the superficial layer, equilibrium and ramp modulus were higher when the samples were loaded parallel to wear-lines (P<0.05). CONCLUSION: These results indicate that mild wear (i.e., wear-line formation) at the articular surface has deleterious functional effects on articular cartilage and represent an early aging-associated degenerative change. The identification and recognition of functional biomechanical consequences of wear-lines are useful for planning and interpreting tensile biomechanical tests in human articular cartilage.

Differential regulation of proteoglycan 4 metabolism in cartilage by IL-1alpha, IGF-I, and TGF-beta1.

OBJECTIVES: To determine (1) if interleukin-1 alpha (IL-1alpha), insulin like growth factor I (IGF-I), and transforming growth factor-beta 1 (TGF-beta1) regulate proteoglycan 4 (PRG4) metabolism in articular cartilage, in terms of chondrocytes expressing PRG4 and PRG4 bound at the articular surface, and (2) if these features of cartilage PRG4 metabolism correlate with its secretion. METHODS: Articular cartilage explants were harvested and cultured for 6 days with or without 10% fetal bovine serum (FBS), alone, or with the addition of 10ng/ml IL-1alpha, 300ng/ml IGF-I, or 10ng/ml TGF-beta1. PRG4 expression by chondrocytes in the cartilage disks was assessed by immunohistochemistry (IHC). PRG4 bound to the articular surface of disks was quantified by extraction and enzyme-linked immunosorbent assay (ELISA). PRG4 secreted into culture medium was quantified by ELISA and characterized by Western Blot. RESULTS: PRG4 expression by chondrocytes near the articular surface was markedly decreased by IL-1alpha, stimulated by TGF-beta1, and not affected by IGF-I. The level of PRG4 accumulation in the culture medium was correlated with the number of chondrocytes expressing PRG4. The amount of PRG4 bound at the articular surface was modulated by incubation in medium including FBS, but did not correlate with levels of PRG4 secretion. CONCLUSIONS: Cartilage secretion of PRG4 is highly regulated by certain cytokines and growth factors, in part through alteration of the number of PRG4-secreting chondrocytes near the articular surface. The biochemical milieu may regulate the PRG4 content of synovial fluid during cartilage injury or repair.

PRG4 exchange between the articular cartilage surface and synovial fluid.

The boundary lubrication function of articular cartilage is mediated in part by proteoglycan 4 (PRG4) molecules, found both in synovial fluid (SF) and bound to the articular cartilage surface. Currently the mechanism by which PRG4 binds to the articular surface is not well understood. The objectives of this study were to determine (1) the effect of bathing fluid contents on PRG4 concentration at the articular surface ([PRG4](cart)), and (2) whether native PRG4 can be removed from the surface and subsequently repleted with PRG4 from synovial fluid. In one experiment, cylindrical cartilage disks were stored in solutions of various PRG4 concentrations, either in phosphate-buffered saline (PBS) or SF as the carrier fluid. In a separate experiment, cartilage disks were stored in solutions expected to remove native PRG4 from the articular surface and allow subsequent repletion with PRG4 from SF. [PRG4](cart) was independent of PRG4 concentration of the bathing fluid, and was similar for both carrier fluids. PRG4 was removed from cartilage by treatment with hyaluronidase, reduction/alkylation, and sodium dodecyl sulphate, and was repleted fully by subsequent bathing in SF. These results suggest that the articular surface is normally saturated with tightly bound PRG4, but this PRG4 can exchange with the PRG4 in SF under certain conditions. This finding suggests that all tissues surrounding the joint cavity that secrete PRG4 into the SF may help to maintain lubrication function at the articular surface.

A model of synovial fluid lubricant composition in normal and injured joints.

The synovial fluid (SF) of joints normally functions as a biological lubricant, providing low-friction and low-wear properties to articulating cartilage surfaces through the putative contributions of proteoglycan 4 (PRG4), hyaluronic acid (HA), and surface active phospholipids (SAPL). These lubricants are secreted by chondrocytes in articular cartilage and synoviocytes in synovium, and concentrated in the synovial space by the semi-permeable synovial lining. A deficiency in this lubricating system may contribute to the erosion of articulating cartilage surfaces in conditions of arthritis. A quantitative intercompartmental model was developed to predict in vivo SF lubricant concentration in the human knee joint. The model consists of a SF compartment that (a) is lined by cells of appropriate types, (b) is bound by a semi-permeable membrane, and (c) contains factors that regulate lubricant secretion. Lubricant concentration was predicted with different chemical regulators of chondrocyte and synoviocyte secretion, and also with therapeutic interventions of joint lavage and HA injection. The model predicted steady-state lubricant concentrations that were within physiologically observed ranges, and which were markedly altered with chemical regulation. The model also predicted that when starting from a zero lubricant concentration after joint lavage, PRG4 reaches steady-state concentration approximately 10-40 times faster than HA. Additionally, analysis of the clearance rate of HA after therapeutic injection into SF predicted that the majority of HA leaves the joint after approximately 1-2 days. This quantitative intercompartmental model allows integration of biophysical processes to identify both environmental factors and clinical therapies that affect SF lubricant composition in whole joints.

Continuous passive motion applied to whole joints stimulates chondrocyte biosynthesis of PRG4.

UNLABELLED: Continuous passive motion (CPM) is currently a part of patient rehabilitation regimens after a variety of orthopedic surgical procedures. While CPM can enhance the joint healing process, the direct effects of CPM on cartilage metabolism remain unknown. Recent in vivo and in vitro observations suggest that mechanical stimuli can regulate articular cartilage metabolism of proteoglycan 4 (PRG4), a putative lubricating and chondroprotective molecule found in synovial fluid and at the articular cartilage surface. OBJECTIVES: (1) Determine the topographical variation in intrinsic cartilage PRG4 secretion. (2) Apply a CPM device to whole joints in bioreactors and assess effects of CPM on PRG4 biosynthesis. METHODS: A bioreactor was developed to apply CPM to bovine stifle joints in vitro. Effects of 24h of CPM on PRG4 biosynthesis were determined. RESULTS: PRG4 secretion rate varied markedly over the joint surface. Rehabilitative joint motion applied in the form of CPM regulated PRG4 biosynthesis, in a manner dependent on the duty cycle of cartilage sliding against opposing tissues. Specifically, in certain regions of the femoral condyle that were continuously or intermittently sliding against meniscus and tibial cartilage during CPM, chondrocyte PRG4 synthesis was higher with CPM than without. CONCLUSIONS: Rehabilitative joint motion, applied in the form of CPM, stimulates chondrocyte PRG4 metabolism. The stimulation of PRG4 synthesis is one mechanism by which CPM may benefit cartilage and joint health in post-operative rehabilitation.

Clinical application of a new disposable lithotripter: a prospective multicenter study.

BACKGROUND: Mechanical lithotripsy has become a well-accepted method of bile duct stone fragmentation and removal. The Olympus lithotripter (Olympus American, Melville, NY) is the standard reusable lithotripter at the institutions that participated in this study. A disposable device with a preassembled pistol grip may perform equally well and facilitate operation. METHODS: Twenty patients with bile duct stones were evaluated as part of a multicenter prospective study. Data were obtained regarding stone size and number, bile duct diameter, and configuration, ease of cannulation, basket function, stone capture and crushing success, and complications. RESULTS: The maximum stone size averaged 16.5 +/- 1.2 mm (range 10 to 30 mm). Sixteen patients had multiple stones (median 5, range 2 to 12). The mean bile duct diameter was 20.5 +/- 1.5 mm (range 12 to 38 mm). Cannulation was successful in all within 5 attempts. Basket deployment failed in 1 patient because of stone size and the basket was misshapen in 14. Bile duct clearance was complete in 16 subjects (80%), incomplete in 2 patients, and failed in 2 patients. Abnormal duct configuration (sigmoid, stricture) was noted in 2 of 4 patients with failed capture and 7 of 16 patients with successful clearance. No statistically significant difference was observed between the bile duct diameter, maximum stone size, number of stones, and successful clearance. CONCLUSION: The disposable lithotripter is easy to use and, compared with the published results for the reusable lithotripter, performs almost as well.

Radiation therapy in a case of systemic mastocytosis: evaluation of histamine levels and mucosal effects.

Plasma histamine levels were obtained during palliative radiation therapy of the spine involved with systemic mastocytosis in a 68-year-old woman. Baseline plasma histamine levels were obtained before irradiation and compared to levels obtained on the third, fifth, eighth, and tenth treatment days. Despite concerns regarding histamine release with mast cell destruction following irradiation, plasma histamine levels remained within normal limits. No change in dermatologic or other systemic manifestations were observed. No untoward systemic or localized sequelae associated with mast cell degranulation in response to the administered large field of radiation was observed. Effective palliation was accomplished, and it was concluded that radiation therapy can effectively be applied in treatment of systemic mast cell disease without significant morbidity.

Lithotripsy versus cholecystectomy for management of gallstones. A decision analysis by Markov process.

Extracorporeal shock-wave lithotripsy is a new treatment method that effectively distintegrates radiolucent gallstones and is associated with a low complication rate. Using the model of a Markov process for decision analysis, survival and costs under four possible strategies to treat gallstones were compared: expectant management with cholecystectomy (EC) or lithotripsy (EL) reserved for symptomatic gallstones; prophylactic cholecystectomy (PC) or lithotripsy (PL) for all gallstones. Life expectancy for the different strategies varies by few days. Only if high annual rates of pain and complication occurred in subjects with silent gallstones would both prophylactic procedures marginally increase life expectancy. Prophylactic cholecystectomy then would be more cost-effective than prophylactic lithotripsy. Expectant strategies remain much cheaper than prophylactic management over a broad range of probability values and procedural costs. Expectant use of lithotripsy costs less than cholecystectomy. A low success rate of lithotripsy would raise the direct costs of lithotripsy above those of cholecystectomy but leave total costs of both strategies in the same order of magnitude. Lithotripsy appears to be a feasible alternative to treat symptomatic but not asymptomatic gallstones.