RESUMEN
Background. Tuberculosis is a disease with continued worldwide prevalence, morbidity, and mortality. Tuberculosis-associated ocular inflammation (TB-AOI) is a manifestation that can occur with pulmonary or extrapulmonary TB. Evaluation of these ocular presentations and treatment in the United States are limited. Our objective was to describe cases in an urban area and assess the role of the infectious diseases specialist in managing these complex patients. Methods. We performed a retrospective case series of all patients referred to our infectious disease clinic for presumed TB-AOI from 2005 through 2013. Patients with ocular inflammation were determined to have presumed TB-AOI based on clinical presentation with correlative positive tuberculin skin test and/or QuantiFERON-TB Gold. Attempts were made to exclude other diagnoses. Data were collected and analyzed with respect to demographics, ocular manifestations, and treatment. Results. Sixty eyes of 42 patients were included in the study; anterior uveitis was the most common site of involvement. The median age was 46 years, and 33 patients (79%) were foreign born. Forty patients (95%) received a course of antituberculous therapy with 38% experiencing treatment-related side effects. A 6-month duration was recommended in 78% cases. There was improvement or stability of the vision in 42 eyes (74%) of those treated. Conclusions. Ocular involvement is an uncommon but important manifestation of TB. Our data further characterize TB-AOI cases in the United States. Treatment provides significant benefit to properly selected patients. A multidisciplinary approach, with care provided by ophthalmology and infectious disease providers, should be used to allow for the most efficacious treatment.
RESUMEN
The aim for deterministic control of the interactions between macroions in aqueous media has motivated widespread experimental and theoretical work. Although it has been well established that like-charged macromolecules can aggregate under the influence of oppositely charged condensing agents, the specific conditions for the stability of such aggregates can only be determined empirically. We examine these conditions, which involve an interplay of electrostatic and osmotic effects, by using a well defined model system composed of F-actin, an anionic rod-like polyelectrolyte, and lysozyme, a cationic globular protein with a charge that can be genetically modified. The structure and stability of actin-lysozyme complexes for different lysozyme charge mutants and salt concentrations are examined by using synchrotron x-ray scattering and molecular dynamics simulations. We provide evidence that supports a structural transition from columnar arrangements of F-actin held together by arrays of lysozyme at the threefold interstitial sites of the actin sublattice to marginally stable complexes in which lysozyme resides at twofold bridging sites between actin. The reduced stability arises from strongly reduced partitioning of salt between the complex and the surrounding solution. Changes in the stability of actin-lysozyme complexes are of biomedical interest because their formation has been reported to contribute to the persistence of airway infections in cystic fibrosis by sequestering antimicrobials such as lysozyme. We present x-ray microscopy results that argue for the existence of actin-lysozyme complexes in cystic fibrosis sputum and demonstrate that, for a wide range of salt conditions, charge-reduced lysozyme is not sequestered in ordered complexes while retaining its bacterial killing activity.