Comprehensive genetic exploration of skeletal dysplasia using targeted exome sequencing.

PURPOSE: The purpose of this study was to evaluate the clinical utility of targeted exome sequencing (TES) as a molecular diagnostic tool for patients with skeletal dysplasia. METHODS: A total of 185 patients either diagnosed with or suspected to have skeletal dysplasia were recruited over a period of 3 years. TES was performed for 255 genes associated with the pathogenesis of skeletal dysplasia, and candidate variants were selected using a bioinformatics analysis. All candidate variants were confirmed by Sanger sequencing, correlation with the phenotype, and a cosegregation study in the family. RESULTS: TES detected "confirmed" or "highly likely" pathogenic sequence variants in 74% (71 of 96) of cases in the assured clinical diagnosis category and 20.3% (13 of 64 cases) of cases in the uncertain clinical diagnosis category. TES successfully detected pathogenic variants in all 25 cases of previously known genotypes. The data also suggested a copy-number variation that led to a molecular diagnosis. CONCLUSION: This study demonstrates the feasibility of TES for the molecular diagnosis of skeletal dysplasia. However, further confirmation is needed for a final molecular diagnosis, including Sanger sequencing of candidate variants with suspected, poorly captured exons.Genet Med 18 6, 563-569.

Prognostic factors of septic arthritis of hip in infants and neonates: minimum 5-year follow-up.

BACKGROUND: The authors conducted the present study to identify clinical and radiological prognostic factors in infants and neonates with septic arthritis of the hip. METHODS: The authors retrospectively reviewed the records of 31 patients with septic arthritis of the hip. All of the patients were younger than 18 months old. Follow-up periods ranged from 5 to 17 years. The following potential variables for predicting the prognosis were included in the assessment: gender, age, underlying diseases, duration of symptoms, changes of hip joint in X-ray, concomitant osteomyelitis, elevation of erythrocyte sedimentation rate and C-reactive protein, sepsis, pus drainage, synovial fluid culture, and infecting organisms. Clinical and radiological prognoses were analyzed at the final follow-up. RESULTS: Univariate analysis demonstrated that radiological prognoses were poorer in patients who had underlying diseases, a longer duration of symptoms, and pus drainage. However, on multivariate analysis, only the variable-duration of symptoms-was found to be statistically related with a poor radiological prognosis. CONCLUSIONS: Although poor prognosis for patients with several underlying diseases and radiological changes has already been established, a favorable outcome might be expected with prompt surgical drainage and appropriate antibiotics.

Repairing the annular ligament is not necessary in the operation of Mason type 2, 3 isolated radial head fractures if the lateral collateral ligament is intact: Minimum 5 years follow-up.

INTRODUCTION: The repair of annular ligament after open reduction and internal fixation of radial head fracture could produce the irritation or crepitation during range of motion exercise. The purpose of this study is to evaluate the significance of unrepaired annular ligament during fixation of isolated radial head fractures. MATERIALS AND METHODS: Retrospectively we reviewed the twenty-five patients who underwent surgical fixation with a plate for Mason type 2, 3 isolated radial head fracture without annular ligament repair. All the radial head fracture did not have the associated injuries which could cause the elbow instabilities. The average length of follow-up was 6.9 years. The outcomes were evaluated clinically (range of motions, instabilities, pain VAS, Broberg & Murrey functional rating score, DASH score) and radiographically (bony union, arthritic change, lateral translation of the radial head, humero-ulnar angle with maximum varus stress of elbow, ulnar variance). RESULTS: The range of motions between affected and contralateral side were not significantly different at last follow-up. No one showed the instabilities of elbow. The mean pain VAS, Broberg & Murrey functional rating score, and DASH score were 2.7±0.5, 95.3±2.5, and 14.8±5.3 points respectively. Bony union was observed for all cases. There was no significant difference in the lateral translation of the radial head, humero-ulnar angle with maximum varus stress of elbow, and ulnar variance between the affected and the contralateral arm. CONCLUSION: The isolated role of the annular ligament seems overestimated. We scrutinize that the annular ligament repair is not essential in the operative treatment of isolated radial head fractures if the lateral collateral ligament is intact.

Percutaneous retrograde intramedullary single wire fixation for metacarpal shaft fracture of the little finger.

This study aimed to evaluate the anatomic and functional outcome of retrograde intramedullary single wire fixation for metacarpal shaft fractures of the little finger. Forty consecutive patients with closed metacarpal shaft fractures of the little finger who have been treated with retrograde intramedullary single wire fixation were evaluated. Fracture union and angulation were analyzed radiologically, and clinical evaluations were performed including the percentage of total active motion (%TAM), disabilities of the arm, shoulder and hand (DASH) score, and complications. Fracture union was achieved in all cases, and callus formation was obvious at 42 days postoperatively. The average angulation of the fracture site was 2.7° in the coronal plane and 1.0° in the sagittal plane at the last follow-up, and no measurable metacarpal shortening was observed. Mean %TAM was 92.0 ± 6.2% (range, 84.6-100%), and DASH score was 2.8 ± 1.2 (range, 0-6). There were two cases of pin migration as intermediate complications. A closed reduction with subsequent percutaneous retrograde K-wire fixation produced good radiological and functional results. We recommend this minimally invasive technique which provides adequate fixation of displaced little finger metacarpal shaft fractures with good functional results and low morbidity.

Percutaneous transphyseal pin fixation through the distal physis of the ulna in pediatric distal fractures of the forearm.

OBJECTIVE: The purpose of this study is to report the long-term results of transphyseal Kirschner (K) wire fixation through the distal physis of ulna in distal fractures of forearm in pediatrics and to determine the safety of this procedure. DESIGN: We performed the study retrospectively. SETTING: All of the patient was treated operatively in the level 2 trauma center. PATIENTS: The medical records and radiographs of 44 pediatric patients who had the distal fractures of forearm retrospectively reviewed. INTERVENTION: After fixation of the radius percutaneously, retrograde percutaneous K-wire fixation through the distal physis of ulna was performed. MAIN OUTCOME MEASUREMENT: At final follow-up, the clinical results according to the system described by Price et al were graded and the range of motion of forearm and wrist was compared with contralateral normal arm. Radiologically, the length discrepancy of ulna and ulnar variance for analysis of premature physis closure was measured. RESULTS: The clinical results were excellent in 31 patients, good in 12, and fair in 1. There was no significant difference in the range of motion of forearm and wrist between arms. Radiologically, there was no evidence of physis closure in all patients. CONCLUSIONS: Retrograde percutaneous transphyseal K-wire fixation through the distal physis of ulna in pediatrics is a minimally invasive and technically easy treatment option.

Effects of corticosteroid on the expressions of neuropeptide and cytokine mRNA and on tenocyte viability in lateral epicondylitis.

BACKGROUND: The purpose of this study was to determine the reaction mechanism of corticosteroid by analyzing the expression patterns of neuropeptides (substance P (SP), calcitonin gene related peptide (CGRP)) and of cytokines (interleukin (IL)-1α, tumor growth factor (TGF)-ß) after corticosteroid treatment in lateral epicondylitis. In addition, we also investigated whether corticosteroid influenced tenocyte viability. METHODS: The corticosteroid triamcinolone acetonide (TAA) was applied to cultured tenocytes of lateral epicondylitis, and the changes in the mRNA expressions of neuropeptides and cytokines and tenocyte viabilities were analyzed at seven time points. Quantitative real-time polymerase chain reaction and an MTT assay were used. RESULTS: The expression of SP mRNA was maximally inhibited by TAA at 24 hours but recovered at 72 hours, and the expressions of CGRP mRNA and IL-1α mRNA were inhibited at 24 and 3 hours, respectively. The expression of TGF-ß mRNA was not significant. Tenocyte viability was significantly reduced by TAA at 24 hours. CONCLUSIONS: We postulate that the reaction mechanism predominantly responsible for symptomatic relief after a corticosteroid injection involves the inhibitions of neuropeptides and cytokines, such as, CGRP and IL-1α. However the tenocyte viability was compromised by a corticosteroid.

Remodeling after lateral closing-wedge osteotomy in children with cubitus varus.

The purpose of this study was to evaluate the effectiveness of supracondylar lateral closing-wedge osteotomy of the humerus in children and the postoperative remodeling of the lateral condylar prominence. Lateral closing-wedge osteotomy for cubitus varus deformity was performed in 52 children. In all cases, medial translation for decreasing lateral condylar prominence or transposition of the ulnar nerve was not performed. Mean patient age was 8.8 years. Mean follow-up was 42 months. Clinical and radiological results were analyzed at last follow-up. Mean range of motion of the elbow in flexion and extension improved significantly (P<.05). Mean humeroulnar angle and mean shaft-condylar angle were significantly corrected (P<.05), and the angles between the affected and contralateral sides were not significantly different at last follow-up. Mean lateral condylar prominence index significantly decreased from 38.8% to 3.4%, and mean lateral condylar prominence amount decreased from -31.6% to -65.0% (P<.05 and P<.05, respectively). The amount of lateral condylar prominence remodeling was statistically correlated with the severity of preoperative cubitus varus, length of follow-up, and age at operation (P<.05 for all). The mean change in lateral condylar prominence amount in patients younger than 11 years (36.6%) was significantly greater than the mean change in lateral condylar prominence amount in patients aged 12 years or older (20.4%) (P=.001). Supracondylar lateral closing wedge osteotomy of the humerus is a simple and effective operation for correction of cubitus varus in children younger than 11 years with a considerable amount of lateral condylar prominence remodeling.

Anterior debridement and strut graft with pedicle screw fixation for pyogenic spondylitis.

STUDY DESIGN: A retrospective study. PURPOSE: We evaluated the results of the use of anterior debridement and interbody fusion followed by posterior spinal instrumentation. OVERVIEW OF LITERATURE: An early diagnosis of pyogenic spondylitis is difficult to obtain. The disease can be treated with various surgical methods (such as anterior debridement and bone graft, anterior instrumentation, and posterior instrumentation). METHODS: This study included 20 patients who received anterior debridement and interbody fusion with strut bone graft followed by posterior spinal fusion for pyogenic spondylitis between 1996 and 2005. We analyzed the culture studies, the correction of the kyphotic angle, blood chemistry, the bony union period, and the amount of symptom relief. RESULTS: In terms of clinical symptoms relief, eight patients were grouped as "excellent", eleven patients as "good", and one patient as "fair". The vertebral body cultures were positive in 14 patients showing coagulase (-) streptococcus and S. aureus. The average times for normalization of the erythrocyte sedimentation rate and C-reactive protein level were 3.3 and 1.9 months, respectively. Four months was required for bony union. For complications, meralgia paresthetica was found in two cases. CONCLUSIONS: Due to early ambulation and the correction of the kyphotic angle, anterior interbody fusion with strut bone graft and posterior instrumentation could be another favorable method for the treatment of pyogenic spondyulitis.

Effects of repeated administration of Uncaria hooks on the acquisition and central neuronal activities in ethanol-treated mice.

The effects of the repeated administration of Uncaria hooks were examined on the impaired memory acquisition and the level of neurotransmitters in the cortex, hippocampus and striatum in ethanol-treated mice, in comparison with those with L-deprenyl and N-methyl-D-glucamine as positive controls. Ethanol-induced amnesia was significantly ameliorated by repeated administration of methanol extract and alkaloid fraction of Uncaria hooks, similar to in the positive controls. Treatment with methanol extract and alkaloid fraction of Uncaria hooks significantly reduced the ethanol-induced increase of dopamine in the hippocampus. The 5-hydroxytryptamine and glutamic acid neuronal activities were significantly changed by Uncaria hooks, but not by L-deprenyl, in all examined brain tissues of ethanol-treated mice. On the other hand, the GABAergic and cholinergic neuronal activities did not show any significant changes by Uncaria hooks in any of the examined brain tissues of the ethanol-treated animals. The results suggest that the extracts of Uncaria hooks exert a beneficial effect on ethanol-induced memory impairment, and that the central 5-hydroxytryptaminergic and glutaminergic neuronal systems play an important role in the memory acquisition of Uncaria hooks.