TSG-6 - a double-edged sword for osteoarthritis (OA).

PURPOSE: To explore mechanisms underlying the association of TSG-6 with osteoarthritis (OA) progression. METHODS: TSG-6-mediated heavy chain (HC) transfer (TSG-6 activity) and its association with inflammatory mediators were quantified in knee OA (n=25) synovial fluids (SFs). Paired intact and damaged cartilages from the same individuals (20 tibial and 12 meniscal) were analyzed by qRT-PCR and immunohistochemistry (IHC) for gene and protein expression of TSG-6 and components of Inter-alpha-Inhibitor (IαI) and TSG-6 activity ± spiked in IαI. Primary chondrocyte cultures (n=5) ± IL1ß or TNFα were evaluated for gene expression. The effects of TSG-6 activity on cartilage extracellular matrix (ECM) assembly were explored using quantitative hyaluronan (HA)-aggrecan binding assays. RESULTS: TSG-6 activity was significantly associated (R > 0.683, P < 0.0002) with inflammatory mediators including TIMP-1, A2M, MMP3, VEGF, VCAM-1, ICAM-1 and IL-6. Although TSG-6 protein and mRNA were highly expressed in damaged articular and meniscal cartilage and cytokine-treated chondrocytes, there was little or no cartilage expression of components of the IαI complex (containing HC1). By IHC, TSG-6 was present throughout lesioned cartilage but HC1 only at lesioned surfaces. TSG-6 impaired HA-aggrecan assembly, but TSG-6 mediated HA-HC formation reduced this negative effect. CONCLUSIONS: TSG-6 activity is a global inflammatory biomarker in knee OA SF. IαI, supplied from outside cartilage, only penetrates the cartilage surface, restricting TSG-6 activity (HC transfer) to this region. Therefore, unopposed TSG-6 in intermediate and deep regions of OA cartilage could possibly block matrix assembly, leading to futile synthesis and account for increased risk of OA progression.

A randomised trial of peri-operative positive airway pressure for postoperative delirium in patients at risk for obstructive sleep apnoea after regional anaesthesia with sedation or general anaesthesia for joint arthroplasty.

Previous pilot work has established an association between obstructive sleep apnoea and the development of acute postoperative delirium , but it remains unclear to what extent this risk factor is modifiable in the 'real world' peri-operative setting. In a single-blind randomised controlled trial, 135 elderly surgical patients at risk for obstructive sleep apnoea were randomly assigned to receive peri-operative continuous positive airway pressure (CPAP) or routine care. Of the 114 patients who completed the study, 21 (18.4%) experienced delirium. Delirium was equally common in both groups: 21% (12 of 58 subjects) in the CPAP group and 16% (9 of 56 subjects) in the routine care group (OR = 1.36 [95%CI 0.52-3.54], p = 0.53). Delirious subjects were slightly older - mean (SD) age 68.9 (10.7) vs. 64.9 (8.2), p = 0.07 - but had nearly identical pre-operative STOP-Bang scores (4.19 (1.1) versus 4.27 (1.3), p = 0.79). Subjects in the CPAP group used their devices for a median (IQR [range]) of 3 (0.25-5 [0-12]) nights pre-operatively (2.9 (0.1-4.8 [0.0-12.7]) hours per night) and 1 (0-2 [0-2]) nights postoperatively (1.4 (0.0-5.1 [0.0-11.6]) hours per night). Among the CPAP subjects, the residual pre-operative apnoea-hypopnea index had a significant effect on delirium severity (p = 0.0002). Although we confirm that apnoea is associated with postoperative delirium, we did not find that providing a short-course of auto-titrating CPAP affected its likelihood or severity. Voluntary adherence to CPAP is particularly poor during the initiation of therapy.

Metabolic deterioration during global ischemia as a function of time in the intact normal dog heart.

High-energy phosphate content and mitochondrial function were analyzed at the initiation and completion of ischemic contracture in dog hearts exposed to normothermic ischemia while on cardiopulmonary bypass. Contracture initiation and completion were detected by a balloon catheter placed within the left ventricle. In seven dogs, inner and outer layers of the myocardium were assayed for adenosine triphosphate (ATP) and creatine phosphate (CP). ATP and CP content in these two layers were compared prior to ischemia and at contracture initiation and completion. Inner layer ATP levels were 23.88 +/- 0.73 (mean +/- SM) mu moles/gm dry weight prior to ischemia, 5.14 +/- 0.49 at initiation, and 0.73 +/- 0.2 at completion. Inner layer CP content was 41.29 +/- 0.87 prior to ischemia, 3.49 +/- 0.34 at initiation, and 4.06 +/- 0.48 at completion. Mitochondrial respiratory control indices (RCI) were assayed in a second group of seven dogs prior to ischemia, at contracture initiation, and at contracture completion and were, respectively, 11.5 +/- 1.18, 3.1 +/- 0.43 and 1.76 +/- 0.29 (alpha ketoglutarate as substrate). Despite the specific degrees of metabolic deterioration associated with the events of contracture, ischemic time required to develop contracture initiation and completion was variable, ranging from 29.5 to 72 minutes for initiation and 60.25 to 101 minutes for completion. A third group of five dogs had biopsy specimens taken for ATP at fixed ischemic time intervals, and at 45 minutes of ischemia they were found to have greater ranges in ATP values than the ranges associated with contracture initiation. In contrast to ischemic time, the physiological events of ischemic contracture are reliable predictors of the degree of metabolic injury in the intact dog heart exposed to normothermic ischemic arrest during cardiopulmonary bypass.

Characteristics of chronic left ventricular hypertrophy induced by subcoronary valvular aortic stenosis. I. Myocardial blood flow and metabolism.

Using a canine model of subcoronary valvular aortic stenosis, we determined myocardial blood flow, high-energy phosphate content, and mitochondrial function in eight hearts with chronic left ventricular hypertrophy. Fourteen normal hearts were used for control data. Myocardial blood flow was determined by injection of tracer microspheres. During cardiopulmonary bypass, left ventricular transmural biopsy specimens were taken for metabolic analyses. Subepicardial and subendocardial content of adenosine triphosphate (ATP) and creatine phosphate (CP) were assayed. Respiratory control indices for isolated mitochondria were measured by use of NAD-linked and FAD-linked substrates. Endocardial blood flow, subendocardial high-energy phosphate content, and respiratory control indices for NAD-linked substrate in the hearts with chronic left ventricular hypertrophy were significantly lower than the normal values. These data provide insight into the metabolic and myocardial blood flow abnormalities occurring in cardiac hypertrophy and provide a framework for understanding the altered response of hypertrophied hearts to ischemia.

Characteristics of chronic left ventricular hypertrophy induced by subcoronary valvular aortic stenosis. II. Response to ischemia.

The increased susceptibility of hearts with chronic left ventricular hypertrophy (CLVH) to damage during ischemia has been suggested but not documented. The purpose of this study was to isolate ischemic events in hearts with CLVH from reperfusion events. Using physiological and biochemical parameters, we compared the rate and extent of myocardial injury during ischemic contracture between eight canine hearts with CLVH induced by subcoronary valvular aortic stenosis and 14 normal canine hearts. Preischemic myocardial blood flow was determined by injection of tracer microspheres. During cardiopulmonary bypass, each heart was instrumented with a left ventricular balloon and made globally ischemic. At control, contracture initiation, and contracture completion left ventricular transmural biopsy specimens were assayed for subepicardial and subendocardial adenosine triphosphate (ATP) and creatine phosphate (CP). Mitochondrial respiratory control indices for NAD-linked and FAD-linked substrates were measured. Preischemic endocardial blood flow in hearts with CLVH was significantly lower than in normal hearts. At control, subendocardial ATP and CP and the respiratory control index for NAD-linked substrate were significantly lower in hearts with CLVH than in normal hearts. Hearts with CLVH reached contracture initiation significantly sooner than normal hearts. All hearts demonstrated significant decreases in high-energy phosphate content and mitochondrial function during ischemia. Reperfusion injury notwithstanding, we concluded that hearts wih CLVH are more susceptible to ischemic injury than are normal hearts, perhaps related to lower endocardial blood flow, lower subendocardial high-energy phosphate stores, and depressed mitochondrial function prior to ischemia.

Myocardial blood flow and oxygen consumption in the empty-beating, fibrillating, and potassium-arrested hypertrophied canine heart.

Myocardial oxygen consumption and blood flow distribution were examined in severely hypertrophied canine hearts in the empty-beating, fibrillating, and pharmacologically arrested states. Hypertrophy was produced using a subcoronary valvular aortic stenosis model that mimics the clinical situation of aortic valvular stenosis. Oxygen content of the total coronary sinus collection was compared with a large volume arterial sample using a Lex-O2-Con-TL analyzer, which had been validated by the Van Slyke-Neill method. Transmural blood flow was measured in each state using microspheres, and perfusion pressure was maintained at 80 mm Hg. Oxygen consumption in the empty-beating hypertrophied heart was found to be the same as that previously reported for normal hearts. Blood flow was evenly distributed in the empty-beating heart, with an endocardial/epicardial ratio of 0.99 +/- 0.15 (SEM) milliliters per minute per gram of left ventricular weight. Oxygen consumption failed to increase significantly with fibrillation; however, blood flow distribution favored the subepicardium, suggesting that oxygen consumption determinations in the fibrillating hypertrophied heart may not accurately reflect metabolic demand. Basal oxygen consumption of the hypertrophied heart as determined by the potassium-arrested, blood-perfused model was the same as that previously described for normal hearts. Blood flow during potassium arrest favored the subendocardium (endocardial/epicardial ratio = 1.14 +/- 0.27 ml/min/gm LV weight).

An improved technique for producing ventricular hypertrophy with a subcoronary valvular aortic stenosis model.

Although techniques for producing aortic valve stenosis proximal to the ostia of the coronary arteries have been described in experimental animals, only moderate left ventricular hypertrophy has been obtained. A technique for plicating the noncoronary sinus of Valsalva in puppies is presented that has enabled us to achieve levels of ventricular hypertrophy not previously reported with methods for subcoronary aortic stenosis.

A biomechanical study of human lateral ankle ligaments and autogenous reconstructive grafts.

The purpose of this study was to investigate the biomechanical behavior of human anterior talofibular and calcaneofibular ligaments, as well as peroneus brevis, split peroneus brevis, and toe extensor tendon grafts. This article represents the first published data comparing the most frequently injured ankle ligaments to the most commonly used autogenous reconstructive grafts. Twenty fresh human ankles provided the bone-ligament-bone and tendon graft specimens for biomechanical testing on a Minneapolis Testing System. Protocol consisted of cyclic loading at physiologic deflections, followed by several load-deflection tests at varying velocities, followed by a final extremely rapid load to failure test. The load-deflection data for all ligaments and tendons demonstrated nonlinearity and strain rate dependence. The maximum load to failure for the anterior talofibular ligament was the lowest of all specimens tested, while its strain to failure was the highest. The loads to failure of the peroneus brevis and split peroneus tendons were significantly greater than the anterior talofibular ligament and approximately equal to the calcaneofibular ligament. Strains to failure for all tendons were significantly less than ligament strains. The high strain to failure of the anterior talofibular ligament demonstrates its physiologic function of allowing increased ankle plantar flexion-internal rotation, while its low load to failure shows its propensity for injury. The greater strength of the tendon grafts explains the success of most reconstructive procedures in reestablishing stability in chronic ankle sprains; at the same time, the data presented suggest that those surgical procedures sacrificing the entire peroneus brevis tendon are unnecessary.(ABSTRACT TRUNCATED AT 250 WORDS)

Lateral condyle fractures: missed diagnoses in pediatric elbow injuries.

Pediatric elbow injuries represent diagnostic dilemmas to all health care personnel. In particular, nondisplaced lateral condyle fractures are often missed when the child first presents for evaluation, and if left untreated, can potentially produce disastrous results. Several illustrative cases are described in order to demonstrate the diagnostic symptoms and signs, as well as the long-term complications associated with the failure to diagnose and institute early treatment. Pertinent clinical findings and elbow anatomy are also reviewed.

Isolated acute hip adductor brevis strain.

Acute muscle strain occurs as a result of an eccentric contraction that exceeds the biomechanical strength of the musculotendinous junction of a single muscle within a synergistic group. To date, only the (hip) adductor longus was shown to sustain this type of injury. In this case report, I describe the first published example of an magnetic resonance imaging (MRI)-documented acute hip adductor brevis strain.

Annular ligament reconstruction in chronic posttraumatic radial head dislocation in children.

Traumatic radial head dislocation without an associated fracture is an unusual injury in children. Occasionally, the diagnosis is missed or the injury is not treated acutely, leading to chronic radial head dislocation. The recommended treatment has been controversial, ranging from benign neglect to surgical reconstruction. This case report and review of the literature describes treatment indications and options, as well as potential risks and benefits for conservative and surgical approaches.

Management of nonunion below proximal humeral prosthesis.

Fractures below proximal humeral prostheses are rare and their successful management presents technical difficulties. Closed treatment usually results in nonunion. A case illustrating this disabling complication is reported and a literature review is presented that summarizes the classification, treatment options, and complications of these uncommon fractures.

Bipolar arthroplasty for recurrent total hip instability.

Bipolar arthroplasty has been reported as a method for correction of recurrent dislocations of total hip replacements. This retrospective review of six patients with multiple dislocations of total hip replacements treated by conversion to simple bipolar hip arthroplasty confirms a 100% success rate in eliminating hip instability during a follow-up period of 2 1/2 to 5 years. However, given the high rate of postoperative discomfort and abnormal gait associated with this procedure, it should be used only when other revision techniques prove to be unsuitable.

Atraumatic floating clavicle and total claviculectomy.

We describe a patient with a floating clavicle of atraumatic origin treated by total claviculectomy. Clavicular function and anatomy are summarized relative to complete excision. Other treatment options for panclavicular instability are also discussed.

Septic sacroiliitis: the overlooked diagnosis.

Infection of the sacroiliac joint is extraordinarily rare. However, the initial symptoms and signs associated with this condition are mundane, thus leading to delay in diagnosis, or even misdiagnosis. I report an extremely unusual pyogenic sacroiliitis caused by Salmonella and discuss key clinical components and protocol for the successful evaluation, diagnosis, and treatment of this uncommon illness.

Conversion of hip arthrodesis to total joint arthroplasty.

Conversion of a hip arthrodesis to a total joint arthroplasty is an uncommon procedure compared to the standard or revision total hip replacement. In this report, two illustrative cases are presented in which conversion to a total joint arthroplasty was performed, and a review of the literature for indications, complications, contraindications, and outcomes of this procedure is provided.

Biomechanical characteristics of human ankle ligaments.

The purpose of this study was to define the biomechanical characteristics of the isolated, individual bone-ligament-bone complexes of the human ankle. Twenty human ankles were dissected of all soft tissues to leave only the tibia, fibula, talus, and calcaneus with their intact anterior talofibular, calcaneofibular, posterior talofibular, and deep deltoid ligaments. Specimens were mounted and tested in a Minneapolis Testing System. Protocol consisted of cyclic loading of each isolated bone-ligament-bone preparation, followed by several constant velocity load-deflection tests at varying deflection rates, followed by a final, extremely rapid load to failure test. All ligaments exhibited nonlinearity and strain rate dependence in their load-deflection data. These properties were correlated with ligament function and trauma. The anterior talofibular ligament, the most commonly injured ankle ligament, had the lowest mean maximum load of the specimens tested, whereas the deep deltoid ligament, the least frequently completely disrupted ankle ligament, had the highest load to failure.