BackgroundDNA methylation has been linked to genome regulation and dysregulation in health and disease respectively, and methods for characterizing genomic DNA methylation patterns are rapidly emerging. We have developed/refined methods for enrichment of methylated genomic fragments using the methyl-binding domain of the human MBD2 protein (MBD2-MBD) followed by analysis with high-density tiling microarrays. This MBD-chip approach was used to characterize DNA methylation patterns across all non-repetitive sequences of human chromosomes 21 and 22 at high-resolution in normal and malignant prostate cells.ResultsExamining this data using computational methods that were designed specifically for DNA methylation tiling array data revealed widespread methylation of both gene promoter and non-promoter regions in cancer and normal cells. In addition to identifying several novel cancer hypermethylated 5' gene upstream regions that mediated epigenetic gene silencing, we also found several hypermethylated 3' gene downstream, intragenic and intergenic regions. The hypermethylated intragenic regions were highly enriched for overlap with intron-exon boundaries, suggesting a possible role in regulation of alternative transcriptional start sites, exon usage and/or splicing. The hypermethylated intergenic regions showed significant enrichment for conservation across vertebrate species. A sampling of these newly identified promoter (ADAMTS1 and SCARF2 genes) and non-promoter (downstream or within DSCR9, C21orf57 and HLCS genes) hypermethylated regions were effective in distinguishing malignant from normal prostate tissues and/or cell lines.ConclusionsComparison of chromosome-wide DNA methylation patterns in normal and malignant prostate cells revealed significant methylation of gene-proximal and conserved intergenic sequences. Such analyses can be easily extended for genome-wide methylation analysis in health and disease.
Purpose Patients with developmental dysplasia of the hip (DDH) may require a pelvic osteotomy to treat acetabular dysplasia. The Pemberton osteotomy and modified San Diego acetabuloplasty are two options available when surgically treating DDH. The purpose of this study was to compare outcomes following the Pemberton and modified San Diego when treating patients with acetabular dysplasia in typical DDH. Methods We included 45 hips in the modified San Diego group and 38 hips in the Pemberton group. Hips with less than two years follow-up and patients with a neuromuscular diagnosis were excluded. Clinical outcomes were rated using the modified McKay criteria with radiographic outcomes graded using the Severin score. Avascular necrosis (AVN) was assessed using the Kalamchi and MacEwen criteria. Results Mean follow-up was 4.9 years (2.1 to 11.2). Both procedures produced similar decreases in the acetabular index (modified San Diego: 17.0˚ versus Pemberton: 15.2˚; p = 0.846). Most hips had good/excellent results using the modified McKay criteria (modified San Diego: 78%, Pemberton: 94%; p = 0.055). Most hips were rated as good/excellent on the Severin scale (modified San Diego: 100%, Pemberton: 97%, p = 0.485). The proportion of hips with AVN grade 2 or higher were similar between groups (modified San Diego: 0%, Pemberton: 3%; p = 0.458). Conclusion The modified San Diego acetabuloplasty is a safe and effective alternative to treat acetabular dysplasia in patients with typical DDH. By maintaining an intact medial cortex, acetabular reshaping can be customized to address each patient’s specific acetabular deficiency Level of evidence Level III retrospective comparison
We demonstrate that a genetic test correlates with bracing outcome. It may be appropriate for future bracing studies to include analysis of genetic predisposition to limit potential confounding.
Background The purpose of this narrative review was to survey the literature for common complications following treatment of DDH in children less than 4 years old. Methods The Pubmed database was queried. Search result titles were reviewed to identify papers that were pertinent to the topic. Abstracts for these papers were obtained and read, and a subset of these were selected for review of the complete manuscript. Results 92 manuscripts were reviewed. Residual dysplasia, redislocation, and osteonecrosis are the primary complications of treatment in this age group. In the long term, hips without complications related to DDH treatment tend to do well, although a significant percentage of them will inevitably require joint replacement surgery. Conclusion Although there is excellent potential for a good outcome when DDH is diagnosed and treated under age 4 years, osteonecrosis continues to be a concern with all treatment methods. A subset of patients from this young cohort will continue to have residual dysplasia or recurrent dislocation requiring return to the operating room.
This study compares clinical, radiographic and patient-reported outcomes among telescoping and traditional screws for the treatment of slipped capital femoral epiphysis (SCFE). We hypothesized that telescoping screws would prevent slip progression and result in preserved femoral neck growth and improved patient-reported outcomes. Traditional screws were compared to telescoping screws in a 2:1 matched cohort based on age at initial surgery, length of radiographic follow-up and whether or not the hip was pinned prophylactically or as a treatment for SCFE. Neck length and telescoping screw length were measured. The patient-reported outcomes were obtained at routine clinic visits. Total 42 hips were included with a mean follow-up of 24.5 ± 3.3 months. No patients developed avascular necrosis, chondrolysis or needed revision surgical procedures. Telescoping screws increased in length for the entire cohort by a mean of 6.0 ± 4.3 mm. Neck length change was not different in SCFE hips when treated with traditional screws vs. telescoping screws (P = 0.527). However, there was a difference in neck length change between the two groups when comparing prophylactically treated hips (P = 0.001). There were no significant differences in patient-reported outcomes among hips treated with telescoping screws compared to traditional screws. Traditional and telescoping screws are both effective for the treatment of SCFE. Telescoping screws have an advantage when prophylactically treating hips that are at risk of slipping as they don’t lead to the coxa breva that is seen with traditional screws. However, both treatment methods had similar patient-reported outcomes.
It appears that the cam deformity was nonexistent among ancient humans and is perhaps predominantly a product of modern-day stresses. Further clinical investigation into behavioral modifications in adolescence is warranted to potentially prevent the development of deformity and impingement.
Background: Increased intracapsular hip pressure is thought to be one of the possible etiologies of femoral head avascular necrosis after intra-articular proximal femoral fractures or acute slipped capital femoral epiphysis. The purpose of this study was to evaluate the relationship between intra-articular hip pressure (IAP) and epiphyseal perfusion pressure (EPP), and its dependency on skeletal maturity using a porcine model. Methods: Seven female Yorkshire-hybrid pigs were used to study the direct relationship between IAP and EPP. A needle inserted into the capsule provided both IAP monitoring and saline infiltration until IAP was above mean arterial pressure (MAP). Video simultaneously documented IAP, EPP, MAP. Parameters for all trials in each hip were averaged and compared between the 2 age groups. Significance was P<0.05. Results: Four young hips (in pigs 10.3±1.0 wk, 27.4±2.0 kg) and 5 older hips (21.1±0.1 wk, 89.4±7.1 kg) were studied. There was no significant difference in the MAP (50.0±11.8 and 55.5±7.0 mm Hg respectively, P=0.411) between the 2 age groups. In the older hips, biphasic EPP persisted despite increasing IAP to an average of 177 mm Hg over MAP. In the young pigs, the biphasic EPP waveform ceased with increased IAP to an average of 28 mm Hg over MAP. Biphasic waveforms returned once IAP fell to an average of 5 mm Hg over MAP. Conclusions: Increased IAP resulted in tamponade of epiphyseal perfusion in the young, but not in the older hips. An intact physis may preclude intraosseous metaphyseal vessels from penetrating the epiphysis, leaving it vulnerable to retinacular artery tamponade. Clinical Relevance: The IAP and EPP relationship has direct clinical practice implications. Hip capsulotomy and decompression in young patients with intra-articular proximal femoral fractures and increased intracapsular pressure may decrease avascular necrosis risk.
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