Ultrasound evaluation of diaphragm motion in BAG-3 myofibrillar myopathy: A case report.

RATIONALE: Mutations in Bcl-2-associated athanogene-3 (BAG-3) can cause a rare subtype of myofibrillar myopathies (MFMs), characterized by progressive muscle weakness, cardiomyopathy, and severe respiratory insufficiency in childhood. Little is known about diaphragmatic function in BAG-3 MFM. To our knowledge, this is the first case report of detailed evaluation of diaphragmatic function with ultrasound in BAG-3 MFM. PATIENT CONCERN: We describe the case of a 15-year-old girl who complained of fever and shortness of breath. Diaphragmatic sonography revealed bilateral diaphragmatic paralysis. Shortness of breath progressed to respiratory failure approximately 3 months later. DIAGNOSIS: A neurologist was consulted and genetic sequencing identified a p.Pro209Leu mutation in BAG-3, yielding diagnosis of BAG-3 MFM leading to bilateral diaphragmatic paralysis. INTERVENTIONS: Respiratory muscle training and long-term mechanical ventilation. OUTCOMES: It is quite unfortunate for this patient to have a poor prognosis due to the lack of effective treatment for this genetic disorder. LESSONS: This case provides more clinical information for this rare disease which may cause severe diaphragm pathological damage leading to respiratory failure in BAG3 MFM and a future study with a systematic evaluation of a greater number of patients will be necessary to characterize this population.

A Hybrid Repair Technique Combining Single-Bundle Reconstruction and Primary Repair With Internal Brace Augmentation for Anterior Cruciate Ligament Injury.

Recently, favorable outcomes of primary anterior cruciate ligament (ACL) repair have been reported in patients with proximal tears and good tissue quality. If the tear involves the midsubstance of the ACL fibers or Sherman type II or III injury, independent primary repair will cause a higher failure rate at long-term follow-up. For these cases, we conduct primary repair and apply an internal brace and single-bundle reconstruction as hybrid augmentation. This hybrid repair technique encourages natural healing of the primary ligament by the internal brace and single-bundle graft as a provisional scaffold during the healing phase, as well as early mobilization. We describe our ACL hybrid repair technique, using a video and illustrations.

Correlation Analysis of Magnetic Resonance Imaging-Based Graft Maturity and Outcomes After Anterior Cruciate Ligament Reconstruction Using International Knee Documentation Committee Score.

OBJECTIVE: The correlation between the signal/noise quotient values of an anterior cruciate ligament graft and the International Knee Documentation Committee Subjective Knee Form 2000 scores after anterior cruciate ligament reconstruction was evaluated. DESIGN: Magnetic resonance imaging and clinical evaluation using International Knee Documentation Committee scores were used to calculate the signal intensity of the graft maturity at the 6-mo and 12-mo follow-up points postoperatively. The associations between the signal/noise quotient values at the 6-mo follow-up point and International Knee Documentation Committee scores at the 12-mo follow-up point were evaluated. RESULTS: A total of 42 male patients completed our trial and returned to normal activity level before the surgery. The mean ± SD age of these patients was 29.07 ± 8.11 yrs (range, 17-47 yrs). The mean ± SD body mass index was 26.00 ± 2.59 kg/m. Notably, the Pearson correlation analysis showed that the International Knee Documentation Committee scores obtained at 12 mos were significantly associated with the signal/noise quotient values measured in the sixth month and twelfth month, respectively (r = -0.454, P = 0.003; r = -0.478, P = 0.001). CONCLUSIONS: According to this study, early measurement of graft maturity might predict the clinical outcome afterward. The sensitive predictive value of signal/noise quotient could be used to maximize the patient outcomes.

Different responses of articular cartilage to strenuous running and joint immobilization.

OBJECTIVE: To compare the pathological changes in cartilage derived from rats that developed osteoarthritis either by joint immobilization or by strenuous treadmill running in order to better understand their respective pathomechanism. METHOD: A total of 24 male Wistar rats were randomly assigned to three groups: sedentary control (CON), immobilization (IM), and strenuous running (SR). For rats in the IM group, unilateral knee joint was immobilized in flexion. Rats in the SR group underwent treadmill running with high intensity. Eight weeks later, all animals were sacrificed. Femoral condyles were collected to take histological observation for cartilage characteristic and immunohistochemistry for collagen type II. In addition, cartilage samples were obtained to assess gene expression of aggrecan, collagen type II, biglycan, and fibromodulin by quantitative RT-PCR. RESULTS: Gross and histological observation showed osteoarthritic changes in groups SR and IM; however, more severe cartilage degradation was revealed in the latter. Proteoglycan and collagen II content decreased in groups SR and IM in comparison to group CON, with more loss in group IM. In group SR, mRNA levels in femoral cartilage were found to be unaltered for all the molecules measured. On the contrary, these molecules were significantly downregulated in group IM. CONCLUSION: Differences in gross observation, histological characteristics, and gene expression of proteoglycans and collagen II suggest that both knee immobilization and strenuous running would lead to degenerative change of cartilage, but at different stages of the degenerative process.

Intensity-dependent effect of treadmill running on knee articular cartilage in a rat model.

OBJECTIVE: To understand the changes of femoral cartilage in response to treadmill running with different intensities in the hope of differentiating "moderate" and "strenuous" running in a rat model. METHOD: A total of 24 male Wistar rats were randomly assigned into groups of sedentary (SED), low-intensity running (LIR), medium-intensity running (MIR), and high-intensity running (HIR). Rats in LIR, MIR, and HIR groups underwent 8 weeks' treadmill running programs. After sacrificed, femoral condyles were collected to take histomorphometric analysis and immunohistochemistry for collagen II. RESULTS: Gross and histological observation showed osteoarthritic changes in group HIR. In comparison to SED group, there was significant increase in cartilage thickness, number of chondrocytes, and GAG content in groups LIR and MIR. Conversely, decrease in cartilage thickness, chondrocyte number, and GAG content was found in rats of HIR group, without significant difference though. In addition, in comparison to SED group, HIR group exhibited disorganization of collagen fibril and significantly lower content of collagen type II. CONCLUSION: An intensity-dependent effect was suggested on the articular cartilage. Our results also demonstrated that running with low-to-medium intensity applied in the present study should be regarded as "moderate" running, whereas high-intensity running as "strenuous" running.

Matrix metalloproteinase-3 inhibitor retards treadmill running-induced cartilage degradation in rats.

INTRODUCTION: The effect of intra-articular injection of matrix metalloproteinase (MMP)-3 inhibitor was investigated in a rat model to understand the role of MMP-3 in cartilage degradation induced by excessive loading from running. METHODS: A total of 24 male Wistar rats were randomly assigned into groups of sedentary control (SED), high-intensity running (HIR), HIR + low dosage of MMP-3 Inhibitor I (HIRI1), and HIR + high dosage of MMP-3 Inhibitor I (HIRI2). Rats in the HIR, HIRI1 and HIRI2 groups were intensively trained for six weeks on the treadmill. Those in HIRI1 and HIRI2 groups were provided bilateral intra-articular injections of 80 µL of 0.2 mM and 2 mM MMP-3 Inhibitor I in knee joints once a week, respectively. Blood samples were collected to measure serum MMP-3 level using ELISA. Femoral condyles were collected to observe cartilage characteristics by histochemistry, and MMP-3 as well as collagen II was measured by immunohistochemistry. In addition, cartilage samples were obtained to assess MMP-3 mRNA expression by RT-PCR. RESULTS: Histological examination showed osteoarthritic changes in rats after six weeks of high intensity running. In comparison to the SED group, significant decreases in glycosaminoglycans (GAG) and collagen content were found in the HIR group, which corresponded to significant increase in serum MMP-3 level, cartilage MMP-3 activity and gene expression. However, such a degradative process was considerably retarded by intra-articular injection of MMP-3 inhibitor at higher dosage. Statistical differences were found between the HIR and HIRI2 groups with regard to GAG and collagen II content, serum MMP-3 level, cartilage MMP-3 activity and gene expression. CONCLUSIONS: High-intensity running for six weeks may lead to cartilage degradation in a rat model. It was shown that the chrondroprotective effect was offered by the use of intra-articular injection of MMP-3 inhibitor. MMP-3 acts as the key mediator of this catabolic change under such mechanical condition. The results also showed that MMP-3 selective inhibitor may be an effective option for retarding such osteoarthritic changes.