Publications (6)18.15 Total impact
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Article: Dll3 and Notch1 genetic interactions model axial segmental and craniofacial malformations of human birth defects.
Developmental Dynamics 07/2008; 237(6):1754. · 2.54 Impact Factor -
Article: De quervain tenosynovitis of the wrist.
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ABSTRACT: De quervain disease, or stenosing tenosynovitis of the first dorsal compartment of the wrist, is a common wrist pathology. Pain results from resisted gliding of the abductor pollicis longus and the extensor pollicis brevis tendons in the fibro-osseus canal. de Quervain tenosynovitis of the wrist is more common in women than men. Diagnosis may be made on physical examination. Radiographs are helpful in ruling out offending bony pathology. Nonsurgical management, consisting of corticosteroid injections and supportive thumb spica splinting, is usually successful. In resistant cases, surgical release of the first dorsal compartment is done, taking care to protect the radial sensory nerve and identify all accessory compartments. Repair of the extensor retinaculum by step-cut lengthening or other techniques is rarely required.The Journal of the American Academy of Orthopaedic Surgeons 01/2008; 15(12):757-64. · 2.66 Impact Factor -
Article: Dll3 and Notch1 genetic interactions model axial segmental and craniofacial malformations of human birth defects
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ABSTRACT: Mutations in the Notch1 receptor and delta-like 3 (Dll3) ligand cause global disruptions in axial segmental patterning. Genetic interactions between members of the notch pathway have previously been shown to cause patterning defects not observed in single gene disruptions. We examined Dll3-Notch1 compound mouse mutants to screen for potential gene interactions. While mice heterozygous at either locus appeared normal, 30% of Dll3-Notch1 double heterozygous animals exhibited localized, segmental anomalies similar to human congenital vertebral defects. Unexpectedly, double heterozygous mice also displayed statistically significant reduction of mandibular height and elongation of maxillary hard palate. Examination of somite-stage embryos and perinatal anatomy and histology did not reveal any organ defects, so we used microarray-based analysis of Dll3 and Notch1 mutant embryos to identify gene targets that may be involved in notch-regulated segmental or craniofacial development. Thus, Dll3-Notch1 double heterozygous mice model human congenital scoliosis and craniofacial disorders. Developmental Dynamics 236:2943–2951, 2007. © 2007 Wiley-Liss, Inc.Developmental Dynamics 09/2007; 236(10):2943 - 2951. · 2.54 Impact Factor -
Article: Primary non-Hodgkin's lymphoma of bone in children.
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ABSTRACT: Primary non-Hodgkin's lymphoma of bone, often more simply referred to as primary lymphoma of bone, is a rare subset of non-Hodgkin's lymphoma in children. There are only a few small series of primary lymphoma of bone in children with long-term follow-up, and none have appeared in the orthopaedic literature. A review of our institution's Pediatric Tumor Registry identified fifteen cases of primary lymphoma of bone among 306 cases of diagnosed non-Hodgkin's lymphoma between 1970 and 2003. Retrospective evaluation included collection of demographic, clinical, radiographic, treatment, and follow-up data. A univariate analysis was used to assess the prognostic significance of risk factors with respect to survival of patients from this series and in a summary analysis of data collected from similar series in the literature. The patients included ten male and five female patients with a mean age of 11.6 years. Most patients had a presenting complaint of pain and had swelling and/or tenderness on physical examination. Eight children had a solitary bone lesion, and seven had multiple bone lesions. Overall, the mean number of bones involved was 3.1 per patient. The femur and the pelvis were the most frequently involved bones. The ten surviving patients were followed for a mean of 13.6 years. Five patients died: three of disease progression, one of treatment-related complications, and one of an unrelated cause. The mean time from diagnosis to death was 2.1 years. Nine patients received chemotherapy only, whereas six patients received a combination of chemotherapy and radiation therapy. In the present study, an age of nine years or less was predictive of poor survival (p < 0.05). In the summary analysis of cases collected from the literature, advanced stage, young age, non-large-cell histology, and multiple-bone involvement were predictive of poor survival (p < 0.05). On the basis of the present series and a comprehensive review of similar series in the literature involving patients with primary lymphoma of bone, it appears that younger age, advanced-stage disease, multiple-bone involvement, and non-large-cell histology are associated with decreased survival as compared with older age, localized disease, single-bone involvement, and large-cell histology, respectively.The Journal of Bone and Joint Surgery 04/2006; 88(3):583-94. · 3.27 Impact Factor -
Article: Developmental anomalies of the cervical spine in patients with fibrodysplasia ossificans progressiva are distinctly different from those in patients with Klippel-Feil syndrome: clues from the BMP signaling pathway.
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ABSTRACT: A radiographic analysis of the cervical spine of 70 patients diagnosed with fibrodysplasia ossificans progressiva (FOP) and 33 diagnosed with Klippel-Feil (KF) syndrome was conducted. The objectives of this study were to describe cervical spine abnormalities in patients with FOP, to compare and contrast those findings with the malformations in patients with KF syndrome, and to examine the possible etiology of these abnormalities. Congenital features of diseases often provide seminal clues to underlying etiology and developmental pathways. While progressive metamorphosis of connective tissue to heterotopic bone is the most dramatic and disabling feature of FOP, less severe congenital anomalies of the skeleton are also present. Vertebral fusions observed in KF are consistent with defects in embryonic segmentation. The cervical spine plain films of 70 FOP patients and 33 KF patients with documented congenital abnormalities were reviewed. Generalized neck stiffness and decreased range of motion were noted in most children with FOP. In the FOP patient group, characteristic anomalies, including large posterior elements, tall narrow vertebral bodies,and fusion of the facet joints between C2 and C7, were observed. Most notably, these characteristic anomalies of the cervical spine in patients with FOP were distinctly different from those of 33 patients with KF that were examined but were strikingly similar to those seen in mice with homozygous deletions of the gene-encoding noggin, a bone morphogenetic protein (BMP) antagonist. FOP patients exhibit a characteristic set of congenital spine malformations. While the noggin gene (NOG) is not mutated in patients who have FOP, these findings extend a growing body of evidence implicating overactivity of the BMP signaling pathway in the molecular pathogenesis of FOP.Spine 07/2005; 30(12):1379-85. · 2.08 Impact Factor -
Article: Molecular analysis of congenital scoliosis: a candidate gene approach.
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ABSTRACT: The etiology of congenital scoliosis is largely unknown. The severe vertebral disorder, spondylocostal dysostosis type 1, is associated with a homozygous delta-like 3 (DLL3) mutation. Scoliosis has been observed in a heterozygous DLL3 carrier, raising the possibility of its involvement in congenital scoliosis. We present the first molecular study of congenital scoliosis by analysis of the candidate gene DLL3 and demonstrate one novel missense variant. However, no novel or previously described mutations are present in our cohort, indicating that DLL3 mutations may not be a major cause of congenital scoliosis. Additionally, we have evaluated patients with congenital scoliosis not diagnosed with a known syndrome and identified a significant number of associated renal and cardiac anomalies and familial incidence of idiopathic scoliosis in this group.Human Genetics 05/2005; 116(5):416-9. · 5.07 Impact Factor
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2005
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The Children's Hospital of Philadelphia
- Department of Orthopaedic Surgery
Philadelphia, PA, USA
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