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.

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.

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.

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.

Heparinas de bajo peso molecular en el embarazo: experiencia clínica en 58 gestaciones / Low molecular weight heparins during pregnancy: clinical experience in 58 pregnancies

El embarazo en mujeres que tienen una enfermedad trombofilica, implica un riesgo de complicaciones trombóticas a nivel sistémico y/o placentario con la consiguiente morbimortalidad materna y pérdidas recurrentes de embarazo. Se estudiaron y trataron 58 embarazos, de 41 mujeres portadoras de estados trombofílicos (41 con sindromes antifosfolipídicos primarios y 5 con trombofilia hereditaria). Las 41 pacientes totalizaban 84 pérdidas recurrentes de embarazos, así como antecedentes de trombosis arteriales y/o venosas. Todos los embarazos fueron tratados con heparinas de bajo peso molecular (HBPM) desde que se confirmó el diagnóstico de embarazo hasta 30-60 días después del parto. La dosis de HBPM fue ajustada para mantener una actividad anti Xa entre 0.2-0.4 UI. Las pacientes que tenían un sindrome antifosfolipídico recibieron además 100 mg/d de aspirina. Los resultados de este estudio mostraron 93.1 por ciento de nacidos vivos, con una mortalidad neonatal de 3.7 por ciento (vinculada a prematurez y bajo peso). No se observaron complicaciones trombóticas ni hemorrágicas en la madre, ni en los bebés. No se observó trombocitopenia ni teratogénesis. Luego del parto, 20 por ciento de las pacientes presentaron una masa ósea disminuida por densitometría. Ninguna de las pacientes tenía estudio densitométrico previo. Una densitometría de control al año mostró normalización de masa ósea en todas las pacientes estudiadas

Acción inhibitoria del Triflusal sobre la agregación plaquetaria in vitro / Inhibitory action of Triflusal on in vitro platelet aggregation

Se estudió el efecto inhibitorio de la droga Triflusal sobre la agregación plaquetaria, en 40 pacientes portadores de patologías vasculares de tipo ateroesclerótico. Se excluyeron diabéticos, pacientes con contraindicaciones digestivas y pacientes que ya estaban tomando otro antiagregante y mostraban una inhibición plaquetaria con dicha droga. Antes de comenzar el tratamiento, el 40 por ciento de los pacientes tenían una hiperfunción plaquetaria in vitro. Los pacientes fueron estudiados antes y después de por lo menos 15 días de tratamiento con Triflusal a la dosis de 900 mg/d vía oral. Se observó que un 77,5 por ciento de la población presentó una inhibición plaquetaria total frente a los inductores ADP y Epinefrina, un 20 por ciento no respondió a la droga en el control in vitro. Cuando el paciente partió con una hiperfunción previa al tratamiento, el porcentaje de pacientes que alcanzó una inhibición plaquetaria total fue menor, 68.7 por ciento. Por el contrario, cuando se partió de un estado de normofunción previa al tratamiento el porcentaje de pacientes que lograron una inhibición plaquetaria total fue mayor alcanzando un 83.3 por ciento de la población estudiada. Efectos secundarios a la administración de la droga se observaron en un 1O por ciento de los pacientes, fueron de tipo digestivo y obligaron a suspender la droga en 2 pacientes con regresión de la sintomatología. Se observó un caso de alergia coincidiendo con la ingestión de la droga que retrocedió al suspenderla

Diagnosis and management of laryngeal trauma in sports.

The management of sports-related laryngeal trauma presents a diagnostic and therapeutic challenge. The application of basic treatment principles such as airway monitoring, thorough physical examination, and fiberoptic laryngeal examination will direct the management. Further radiologic examination or surgical intervention may be required to adequately assess and manage the injury. We review the diagnosis, treatment, and management in a case of laryngeal fracture that occurred during a National Hockey League game.

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.

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.

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.

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.

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)

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.

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).

Depressed high-energy phosphate content in hypertrophied ventricles of animal and man: the biologic basis for increased sensitivity to ischemic injury.

It is frequently stated that hypertrophied ventricles tolerate ischemia less well than nonhypertrophied ventricles. The authors' earlier studies in a rat supravalvular aortic stenosis model and canine valvular aortic stenosis model, both with concentric left ventricular hypertrophy, disclosed accelerated rates of ischemic contracture and diminished basal myocardial high energy phosphate stores. These studies have been extended to ten patients with severe left ventricular hypertrophy caused by valvular aortic stenosis and normal coronary arteries. ATP (endocardial and epicardial) from transmural left ventricular biopsies taken at operation before aorta cross-clamping, and frozen immediately in liquid nitrogen, were compared with similar biopsies from patients with nonhypertrophied myocardium supplied by normal coronary arteries. The subendocardial high energy phosphate levels in the nonhypertrophied myocardium was greater than high energy phosphate levels in the subepicardium of nonhypertrophied ventricles (ATP-micromoles/gram-protein, epi = 36.8 +/- 3.3, endo = 37.7 +/- 3.3) (p = NS). However, in the hypertrophied myocardium the subendocardium consistently showed significantly depressed high-energy phosphate levels when compared with subepicardial levels (ATP-hypertrophied myocardium, epi = 31.5 +/- 1.6, endo = 25.9 +/- 1.7) (p less than 0.05). This uniform depression of ATP stores, greatest in the subendocardium, in left ventricular hypertrophy suggests a common biologic mechanism for the enhanced sensitivity to ischemia. Of importance for patients may be the prior observation in rats that repletion of ATP( stores before ischemia eliminates the accelerated rate to ischemic contracture. Diminished subendocardial ATP stores appear to be an intrinsic property of severely hypertrophied myocardium and probably contribute to its enhanced sensitivity to ischemia.