Citations

Abstract Arthroscopic debridement is a reliable and effective treatment for knee arthritis in appropriately selected patients. Debridement may include lavage, loose body removal, partial meniscectomy, and/or chondroplasty. Patient selection criteria include acute effusion, well localized joint line tenderness, or catching or locking, often associated with a specific mechanism of injury, patients with imaging studies confirming loose bodies, patients with earlier stages of degenerative joint disease, and patients with realistic understanding that the goal of arthroscopy is to diminish pain and improve function and not to cure their arthritis. Surgeons are cautioned, in patients with an osteoarthritic knee, MRI may be overly sensitive and inadequately specific with regard to correlation between pathologic findings (with the exception of loose bodies) and predictably treatable disease. In conclusion, the authors cite the Arthroscopy Association of North America Position Statement on Osteoarthritis: “There is…a sub‐group of patients with knee arthritis that can be significantly helped with appropriate arthroscopic surgery.”

ABSTRACT Rhino-orbitocerebral mucormycosis (ROCM) caused by more common zygomycetes (e.g., Mucor ) is known to cause rapidly fatal infections in immunocompromised patients. Apophysomyces elegans is an emerging zygomycete that has been reported to cause invasive cutaneous and rhino-orbitocerebral infections in immunocompetent individuals. Limited data exist describing the syndrome of ROCM caused by A. elegans . We describe a recent case and performed a comprehensive literature review to delineate the clinical characteristics of ROCM caused by A. elegans . Our case is a 50-year-old man with diabetes mellitus who presented with facial pain and right eye proptosis. Endoscopic sinus sampling revealed A. elegans . He was treated with liposomal amphotericin B and multiple debridements, with no disease on 1.5-year follow-up examination. Seven cases were identified on literature review, including the present case. Most patients (86%) were male, with a mean age of 40 years. Most patients (71%) did not have predisposing medical conditions. Three patients had predisposing head trauma. All presented with facial and/or periorbital pain. All had magnetic resonance imaging or computed tomography of the head showing intraorbital and/or sinus inflammation. Diagnosis was confirmed by histopathology and deep tissue culture in all cases. All patients required eye exenteration and extensive surgical debridement, in addition to intravenous amphotericin B. Six of the seven patients (86%) recovered. ROCM caused by A. elegans is rarely reported in the literature. Most such infections occurred in immunocompetent patients, often after facial trauma. Survival in ROCM caused by A. elegans is favorable in reported cases, with prompt surgical debridement and antifungal therapy.

AbstractUnderstanding of the conformational changes in G protein-coupled receptors associated with activation and inactivation is of great interest. We previously used photoaffinity labeling to elucidate spatial approximations between photolabile residues situated throughout the pharmacophore of secretin agonist probes and this receptor. The aim of the current work was to develop analogous photolabile secretin antagonist probes and to explore their spatial approximations. The most potent secretin antagonist reported is a pseudopeptide ([ψ4, 5]secretin) in which the peptide bond between residues 4 and 5 was replaced by a ψ(CH2-NH) peptide bond isostere. We have developed a series of [ψ4, 5]secretin analogs incorporating photolabile benzoyl phenylalanine residues in positions 6, 22, and 26. Each bound to the secretin receptor saturably and specifically, with affinity similar to their parental peptide. At concentrations with no measurable agonist activity, each probe covalently labeled the secretin receptor. Peptide mapping using proteolytic cleavage, immunoprecipitation, and radiochemical sequencing identified that each of these three probes labeled the amino terminus of the secretin receptor. Whereas the position 22 probe labeled the same residue as its analogous agonist probe and the position 6 probe labeled a residue within two residues of that labeled by its analogous agonist probe, the position 26 probe labeled a site 16 residues away from that labeled by its analogous agonist probe. Thus, whereas structurally related agonist and antagonist probes dock in the same general region of this receptor, conformational differences in active and inactive states result in substantial differences in spatial approximation at the carboxyl-terminal end of secretin analogs.

Abstract Rationale: Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with substantial morbidity, and standard daily multidrug therapy is difficult to tolerate. Objectives To characterize response to a three-times-weekly (TIW) regimen of clarithromycin, ethambutol, and rifampin. Methods A 1-yr prospective noncomparative trial of TIW treatment was conducted during 2000–2003 in 17 U.S. cities. Participants were 91 HIV-negative adults, diagnosed with moderate to severe MAC-PD, who originally participated in a trial of an inhaled IFN-γ treatment. Improvement in sputum culture, high-resolution computed tomography (HRCT), and symptoms were assessed. Results Treatment response rates (and median response times) were 44% (2 mo or longer) for culture, 60% (5.5–11.5 mo) for HRCT, and 53% (8.5 mo) for symptoms. Having noncavitary, compared with cavitary, disease increased culture response by 4.0 times (95% confidence interval [CI], 1.7–9.2) and HRCT response by 4.9 times (95% CI, 1.9–13.0). Culture response was 1.5 times (95% CI, 1.1–2.2) higher for older subjects and 2.2 times (95% CI, 1.0–4.7) higher for previously untreated subjects. Being smear-negative increased culture response by 2.3 times (95% CI, 1.1–5.2) but decreased HRCT response by 4.4 times (95% CI, 1.7–11.5). Increasing ethambutol use by 5 mo increased culture response by 1.5 times (95% CI, 1.0–2.1) but decreased symptom response. Not having chronic obstructive pulmonary disease, bronchiectasis, or poor lung function increased symptom response by 1.9 to 3.9 times. Conclusions TIW therapy was less effective for MAC-PD patients with cavitary disease and a history of chronic obstructive pulmonary disease, bronchiectasis, or previous treatment for MAC-PD. Further research is needed to study the long-term outcomes of TIW treatment.