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Tian Q.Y.,NYU Hospital for Joint Diseases
Journal of visualized experiments : JoVE | Year: 2012

Progranulin (PGRN), also known as granulin epithelin precursor (GEP), is a 593-amino-acid autocrine growth factor. PGRN is known to play a critical role in a variety of physiologic and disease processes, including early embryogenesis, wound healing, inflammation, and host defense. PGRN also functions as a neurotrophic factor, and mutations in the PGRN gene resulting in partial loss of the PGRN protein cause frontotemporal dementia. Our recent studies have led to the isolation of PGRN as an important regulator of cartilage development and degradation. Although PGRN, discovered nearly two decades ago, plays crucial roles in multiple physiological and pathological conditions, efforts to exploit the actions of PGRN and understand the mechanisms involved have been significantly hampered by our inability to identify its binding receptor(s). To address this issue, we developed a modified yeast two-hybrid (MY2H) approach based on the most commonly used GAL4 based 2-hybrid system. Compared with the conventional yeast two-hybrid screen, MY2H dramatically shortens the screen process and reduces the number of false positive clones. In addition, this approach is reproducible and reliable, and we have successfully employed this system in isolating the binding proteins of various baits, including ion channel, extracellular matrix protein, and growth factor. In this paper, we describe this MY2H experimental procedure in detail using PGRN as an example that led to the identification of TNFR2 as the first known PGRN-associated receptor.

Jain M.,NYU Hospital for Joint Diseases | Samuels J.,NYU Langone Medical Center
Bulletin of the NYU Hospital for Joint Diseases | Year: 2010

The use of musculoskeletal ultrasound (MSKUS) in rheumatology practice and research has increased steadily over the last decade. An ever-growing body of literature shows parity and even superiority of MSKUS when compared to physical examination, plain radiography, and more expensive and static imaging modalities such as MRI. While many use the modality for procedure guidance, investigators continue to demonstrate its ability to impact diagnoses in a variety of rheumatic diseases. Initial efforts focused on establishing MSKUS as a helpful tool for rheumatoid arthritis (RA), especially in the detection of synovitis and joint erosions, but numerous studies are validating the use of MSKUS as a helpful diagnostic tool for the spondyloarthropathies, crystal diseases, osteoarthritis, and other rheumatic diseases. Advances in ultrasound technology are translating into more sensitive and accurate studies. Within the research community, current efforts aim at maximizing the direct clinical impact of MSKUS by developing global or patient- level assessments and simplified joint scoring systems, with improvements in intra- and inter-reader reproducibility.

Yazici Y.,NYU Hospital for Joint Diseases | Curtis J.R.,University of Alabama at Birmingham | Baraf H.,Center for Rheumatology and Bone Research | Malamet R.L.,Genentech | And 2 more authors.
Annals of the Rheumatic Diseases | Year: 2012

Objectives: To evaluate efficacy of tocilizumab in US patients with moderate to severe active rheumatoid arthritis (RA) and inadequate clinical response to disease-modifying antirheumatic drugs (DMARD). Safety-related outcomes were also analysed. Methods: The rapid onset and systemic efficacy study was a 24-week, randomised, double-blind trial. Patients were randomly assigned 2:1 to tocilizumab 8 mg/kg (n=412) or placebo (n=207) every 4 weeks while continuing background DMARD in both groups. Results: The primary efficacy endpoint, percentage of patients achieving ACR50 response at week 24, was higher with tocilizumab versus placebo (30.1% vs 11.2%; p<0.0001). Percentages of ACR20 and ACR50 responders were significantly higher with tocilizumab versus placebo as early as week 4 and continued to week 24; more patients in the tocilizumab versus placebo group also achieved ACR70 responses beginning at week 8 (p<0.01). Significant improvements associated with tocilizumab versus placebo were seen in routine assessment of patient index data responses, EULAR good response, DAS28 and percentages of patients achieving low disease activity and clinical remission (based on DAS28). A substudy examining early response to therapy showed improved patient global assessment of disease activity (p=0.005) and pain (p=0.01) and DAS28 (p=0.007) with tocilizumab versus placebo at day 7. Safety findings were consistent with the known tocilizumab safety profile; rates of serious infections (per 100 patient-years) were 7.87 (95% CI 4.30 to 13.2) and 1.20 (95% CI 0.03 to 6.66) in the tocilizumab and placebo groups, respectively. Conclusions: This study demonstrated the efficacy of tocilizumab in improving measures of disease activity in patients with RA who failed to respond adequately to DMARD therapy. Rapid improvement in clinical outcomes was demonstrated in a substudy as early as week 1 as shown by DAS28 scores, patient measures and C-reactive protein. Trial Registry no: NCT00531817.

Nord R.M.,NYU Hospital for Joint Diseases | Nord R.M.,Washington Township Orthopedic Surgery and Sports Medicine Center | Meislin R.J.,NYU Langone Medical Center
Bulletin of the NYU Hospital for Joint Diseases | Year: 2010

The acceptance and rates of hip arthroscopy are increasing in the United States and abroad and the literature describing it is expanding. Indications for hip arthroscopy include labral tears, loose bodies, femoroacetabular impingement, ruptured ligamentum teres, chondral injuries, adhesive capsulitis, instability, synovial disease, disorders of the iliopsoas tendon, external coxa saltans, tears of the hip abductors, and diagnosis of unresolved intra-articular hip pain. Current techniques in the central and peripheral compartments include, but are not limited to, labral debridement, labral repair, chondroplasty, microfracture, synovectomy, loose body removal, acetabuloplasty, proximal femoral osteoplasty, and iliopsoas release, with other procedures possible in the peritrochanteric space. Long-term outcomes are limited, but early data shows good results for many arthroscopic procedures in the hip when they are performed in the absence of degenerative disease. Improved techniques and technology are allowing for more advanced procedures to become popularized, but long-term outcome data about hip arthroscopy is still relatively sparse.

Catanzano A.,NYU Hospital for Joint Diseases | Phillips M.,NYU Hospital for Joint Diseases | Dubrovskaya Y.,NYU Hospital for Joint Diseases | Hutzler L.,NYU Hospital for Joint Diseases | Bosco J.,3rd
The Iowa orthopaedic journal | Year: 2014

INTRODUCTION: The indications for vancomycin prophylaxis to prevent Methicillin-resistant Staphylococcus aureus (MRSA) surgical site infections are increasing. The recommended dose of vancomycin has traditionally been 1 gram intravenous. However, the increasing prevalence of obesity in our population coupled with increasing resistance of MRSA to vancomycin has resulted in recent recommendations for weight-based dosing of vancomycin at 15 mg/kg. We hypothesize that the standard one gram dose of vancomycin is inadequate to meet the recently recommended dosage of 15 mg/kg.METHODS: We performed a retrospective chart review on 216 patients who were screened positive for MRSA prior to undergoing elective total joint or spine surgeries between January 2009 to January 2012. All patients were given 1 gram of vancomycin within an hour prior to surgical incision as prophylaxis. Using the revised dosing protocol of 15 mg/kg of body weight for vancomycin, proper dosage was calculated for each patient. These values were then compared to the 1 gram dose given to the patients at time of surgery. Patients were assessed as either underdosed (a calculated weight-based dose >1 gram) or overdosed (a calculated weight-based dose <1 gram). Additionally, we used actual case times and pharmacokinetic equations to determine the vancomycin (VAN) levels at the end of the procedures.RESULTS: Out of 216 patients who tested positive for MRSA, 149 patients (69%) were determined to be underdosed and 22 patients (10%) patients were determined to be overdosed. The predicted VAN level at the end of procedure was <15 mg/L in 60% of patients with 1 gram dose compared to 12% (p=0.0005) with weight base dose. Six patients developed post-operative MRSA surgical site infections (SSI). Of these six patients; four had strains of MRSA with vancomycin minimum inhibitory concentration of >1.0 mg/L. Based on 1 g dosing, 5/6 patients with MRSA positive SSIs had wound closure levels of <15 mg/L and all six were <20 mg/L.CONCLUSION: In settings such as hospitals, where the risk for resistant bacteria, especially MRSA, is high, it is becoming increasingly important to accurately dose patients who require vancomycin. In order to avoid incorrect dosing of vancomycin health care providers must use weight-based dosing.

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