Treatment of hallux valgus by modified McBride procedure: a 6-year follow-up

PubMed ID: 20505975Background Surgical decision-making was reevaluated by comparison with an algorithm designed to analyze treatment of hallux valgus deformities. Materials and methods A modified McBride procedure was performed on 52 feet of 35 patients with hallux valgusdeformity. From this series, 36 feet of 21 patients were evaluated preoperatively, early postoperatively, and late postoperatively by means of subjective evaluation and clinical and radiological findings. Results The hallux valgus angle preoperatively, early postoperatively, and late postoperatively was 32.7 ± 8.5°, 10.1 ± 6.9°, and 20.6 ± 9.5°, respectively. Hallux valgus recurrence of 72.2% was observed. Subjective results were better and the patients rated their satisfaction with the procedure as excellent or high in 23 cases (63.9%) and moderate, low, or unsatisfactory in 13 cases (36.1%). Conclusions This level of patient satisfaction demonstrates that the McBride procedure is an efficient approach for eliminating pain due to hallux valgus deformity. © The Author(s) 2010

Treatment of hallux valgus by modified McBride procedure: a 6-year follow-up

PubMed ID: 20505975Background Surgical decision-making was reevaluated by comparison with an algorithm designed to analyze treatment of hallux valgus deformities. Materials and methods A modified McBride procedure was performed on 52 feet of 35 patients with hallux valgusdeformity. From this series, 36 feet of 21 patients were evaluated preoperatively, early postoperatively, and late postoperatively by means of subjective evaluation and clinical and radiological findings. Results The hallux valgus angle preoperatively, early postoperatively, and late postoperatively was 32.7 ± 8.5°, 10.1 ± 6.9°, and 20.6 ± 9.5°, respectively. Hallux valgus recurrence of 72.2% was observed. Subjective results were better and the patients rated their satisfaction with the procedure as excellent or high in 23 cases (63.9%) and moderate, low, or unsatisfactory in 13 cases (36.1%). Conclusions This level of patient satisfaction demonstrates that the McBride procedure is an efficient approach for eliminating pain due to hallux valgus deformity. © The Author(s) 2010

Hot Start PCR with heat-activatable primers: a novel approach for improved PCR performance

The polymerase chain reaction (PCR) is widely used for applications which require a high level of specificity and reliability, such as genetic testing, clinical diagnostics, blood screening, forensics and biodefense. Great improvements to PCR performance have been achieved by the use of Hot Start activation strategies that aim to prevent DNA polymerase extension until more stringent, higher temperatures are reached. Herein we present a novel Hot Start activation approach in PCR where primers contain one or two thermolabile, 4-oxo-1-pentyl (OXP) phosphotriester (PTE) modification groups at 3′-terminal and 3′-penultimate internucleotide linkages. Studies demonstrated that the presence of one or more OXP PTE modifications impaired DNA polymerase primer extension at the lower temperatures that exist prior to PCR amplification. Furthermore, incubation of the OXP-modified primers at elevated temperatures was found to produce the corresponding unmodified phosphodiester (PDE) primer, which was then a suitable DNA polymerase substrate. The OXP-modified primers were tested in conventional PCR with endpoint detection, in one-step reverse transcription (RT)–PCR and in real-time PCR with SYBR Green I dye and Taqman® probe detection. When OXP-modified primers were used as substitutes for unmodified PDE primers in PCR, significant improvement was observed in the specificity and efficiency of nucleic acid target amplification

Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA damage-response pathway in SCA3.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an untreatable autosomal dominant neurodegenerative disease, and the most common such inherited ataxia worldwide. The mutation in SCA3 is the expansion of a polymorphic CAG tri-nucleotide repeat sequence in the C-terminal coding region of the ATXN3 gene at chromosomal locus 14q32.1. The mutant ATXN3 protein encoding expanded glutamine (polyQ) sequences interacts with multiple proteins in vivo, and is deposited as aggregates in the SCA3 brain. A large body of literature suggests that the loss of function of the native ATNX3-interacting proteins that are deposited in the polyQ aggregates contributes to cellular toxicity, systemic neurodegeneration and the pathogenic mechanism in SCA3. Nonetheless, a significant understanding of the disease etiology of SCA3, the molecular mechanism by which the polyQ expansions in the mutant ATXN3 induce neurodegeneration in SCA3 has remained elusive. In the present study, we show that the essential DNA strand break repair enzyme PNKP (polynucleotide kinase 3'-phosphatase) interacts with, and is inactivated by, the mutant ATXN3, resulting in inefficient DNA repair, persistent accumulation of DNA damage/strand breaks, and subsequent chronic activation of the DNA damage-response ataxia telangiectasia-mutated (ATM) signaling pathway in SCA3. We report that persistent accumulation of DNA damage/strand breaks and chronic activation of the serine/threonine kinase ATM and the downstream p53 and protein kinase C-d pro-apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in SCA3. Either PNKP overexpression or pharmacological inhibition of ATM dramatically blocked mutant ATXN3-mediated cell death. Discovery of the mechanism by which mutant ATXN3 induces DNA damage and amplifies the pro-death signaling pathways provides a molecular basis for neurodegeneration due to PNKP inactivation in SCA3, and for the first time offers a possible approach to treatment.This study was funded by NIH grant NS073976 to TKH and a John Sealy Grant to PSS