Evaluation of human leukocyte N-formylpeptide receptor (FPR1) SNPs in aggressive periodontitis patients

Made available in DSpace on 2019-09-12T16:53:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2003National Institute of Dental and Craniofacial Research (NIDCR)Polymorphonuclear neutrophils (PMNs) are attracted to sites of infection by N-formylpeptide (fMLP) chemoattractants. The high-affinity fMLP receptor (FPR1) of phagocytic cells interacts with bacterial fMLP and mediates chemotaxis, degranulation, and superoxide production. These cellular functions are disrupted in PMN from aggressive periodontitis (AP) patients. Two FPR1 gene single nucteotide polymorphisms (SNPs), c.329T> C and c.378C> G, have been associated with a localized form of AP in African-American patients. To evaluate the generality of these SNPs in AP patients, we sequenced a 363 bp interval of the FPR1 gene in an ethnically diverse group of patients (n = 111) and controls (n = 115). Neither c.329T> C nor c.378C> G were detected in the 452 alleles sequenced. Six SNPs were identified including two located in the FPR1 second extracellular loop that were significantly associated with the AP phenotype in African-American patients (p.R190W, P = 0.0033; and p.N192K, P = 0.0018). These two SNPs show three predominant haplotypes, each associated with a different disease risk in African-Americans. These data do not support the hypothesis that the FPR1 SNPs c.329T> C and c.378C> G play an etiologic role in aggressive periodontitis, but do suggest that SNPs in the second extracellular loop may be etiologically important.Univ Pittsburgh, Sch Dent Med, Ctr Craniofacial & Dent Genet, Pittsburgh, PA 15261 USA; Universidade de Taubaté (Unitau), Sch Dent, Dept Periodont; Univ Istanbul, Sch Dent, Dept Periodontol, Istanbul, Turkey; Boston Univ, Goldman Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA 02118 USA; Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 US

Optilume drug‐coated balloon for anterior urethral stricture: 2‐year results of the ROBUST III trial

Abstract Objective The aim of this study is to report the updated 2‐year results of the intervention arm of the ROBUST III randomized trial evaluating the safety and efficacy of the Optilume drug‐coated balloon (DCB) versus standard endoscopic management of recurrent male anterior urethral stricture. Materials and Methods Eligible patients included men with recurrent anterior urethral stricture ≤3 cm in length and ≤12Fr in diameter, International Prostate Symptom Score (IPSS) ≥11 and peak flow rate (Qmax) <15 mL/s. Patients were randomized to treatment with the Optilume DCB or standard‐of‐care endoscopic management. Primary efficacy endpoints measured at 2 years included freedom from re‐intervention and changes in IPSS, Qmax and post‐void residual (PVR). Secondary endpoint was impact on sexual function using the International Index of Erectile Function (IIEF). Primary safety endpoint was freedom from serious procedure‐ or device‐related adverse events (AEs). Results A total of 127 patients enrolled at 22 sites in the United States and Canada (48 randomized to standard‐of‐care dilation and 79 to DCB dilation). Seventy‐five patients in the DCB arm entered the open‐label phase after 6 months. Participants averaged 3.2 prior endoscopic interventions (range 2–10); most (89.9%) had bulbar strictures with an average stricture length of 1.63 cm (SD 0.76). Significant improvements in IPSS, average Qmax and PVR were maintained at 2 years. Freedom from repeat intervention was significantly higher in the Optilume DCB arm at 2 years versus the Control arm at 1 year (77.8% vs. 23.6%, p < 0.001). During the follow‐up period, there were 15 treatment failures and two non‐study‐related deaths. Treatment‐related AEs were rare and generally self‐limited (haematuria, dysuria and urinary tract infection). Conclusion The Optilume DCB shows sustained improvement in both objective and subjective voiding parameters at 2‐year follow‐up. Optilume appears to provide a safe and effective endoscopic treatment alternative for short recurrent anterior urethral strictures among men who wish to avoid or delay formal urethroplasty