RESUMEN
Mycobacterium tuberculosis (M.tb) is deposited into the alveolus where it first encounters the alveolar lining fluid (ALF) prior contacts host cells. We demonstrated that M.tb-exposure to human ALF alters its cell surface, driving better M.tb infection control by professional phagocytes. Contrary to these findings, our results with non-professional phagocytes alveolar epithelial cells (ATs) define two distinct subsets of human ALFs; where M.tb exposure to Low (L)-ALF or High(H)-ALF results in low or high intracellular bacterial growth rates in ATs, respectively. H-ALF exposed-M.tb growth within ATs was independent of M.tb-uptake, M.tb-trafficking, and M.tb-infection induced cytotoxicity; however, it was associated with enhanced bacterial replication within LAMP-1+/ABCA1+ compartments. H-ALF exposed-M.tb infection of ATs decreased AT immune mediator production, decreased AT surface adhesion expression, and downregulated macrophage inflammatory responses. Composition analysis of H-ALF vs. L-ALF showed H-ALF with higher protein tyrosine nitration and less functional ALF-innate proteins important in M.tb pathogenesis. Replenishment of H-ALF with functional ALF-innate proteins reversed the H-ALF-M.tb growth rate to the levels observed for L-ALF-M.tb. These results indicate that dysfunctionality of innate proteins in the H-ALF phenotype promotes M.tb replication within ATs, while limiting inflammation and phagocyte activation, thus potentiating ATs as a reservoir for M.tb replication and survival.
Asunto(s)
ADN Bacteriano/genética , Células Epiteliales/fisiología , Pulmón/patología , Mycobacterium tuberculosis/fisiología , Alveolos Pulmonares/patología , Mucosa Respiratoria/inmunología , Tuberculosis Pulmonar/inmunología , Células A549 , Apoptosis , Adhesión Celular , Citotoxicidad Inmunológica , Replicación del ADN , Células Epiteliales/inmunología , Humanos , Inmunidad Innata , Pulmón/microbiología , Fagocitosis , Alveolos Pulmonares/inmunologíaRESUMEN
Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis, is a major public health challenge facing the world. During infection, M.tb is deposited in the lung alveolar space where it comes in contact with the lung mucosa, known as alveolar lining fluid (ALF), an environment that M.tb encounters at different stages of the infection and disease. ALF is abundant in homeostatic and antimicrobial hydrolytic enzymes, also known as hydrolases. Here we demonstrate that ALF hydrolases, at their physiological concentrations and upon contact with M.tb, release M.tb cell envelope fragments into the milieu. These released fragments are bioactive, but non-cytotoxic, regulate the function of macrophages, and thus are capable of modulating the immune response contributing to the control of M.tb infection by human macrophages. Specifically, macrophages exposed to fragments derived from the exposure of M.tb to ALF were able to control the infection primarily by increasing phagosome-lysosome fusion and acidification events. This enhanced control was found to be dependent on fragment-induced interleukin-10 (IL-10) production but also involves the STAT3 signaling pathway in an IL-10-independent manner. Collectively our data indicate that M.tb fragments released upon contact with lung mucosa hydrolases participate in the host immune response to M.tb infection through innate immune modulation.
Asunto(s)
Pared Celular/metabolismo , Macrófagos/inmunología , Mycobacterium tuberculosis/inmunología , Mucosa Respiratoria/metabolismo , Tuberculosis Pulmonar/inmunología , Células Cultivadas , Humanos , Hidrolasas/metabolismo , Inmunidad Innata , Interleucina-10/metabolismo , Lisosomas/metabolismo , Macrófagos/microbiología , Fusión de Membrana , Fagocitosis , Fagosomas/metabolismo , Mucosa Respiratoria/patología , Factor de Transcripción STAT3/metabolismoRESUMEN
OBJECTIVE: To evaluate the influence of socio-economic factors on severity of glaucoma at presentation METHODS: All newly diagnosed glaucoma patients at the University Hospitals-NHS, Aberdeen and South Glasgow University Hospitals-NHS, in 2006, were included. Glaucoma was severe at presentation if there was a repeatable visual-field loss with a mean deviation index greater than 12 dB in the Humphreys visual fields test or an absolute paracentral scotoma within the central 5 degrees of the visual fields. Home address was used to determine the Scottish Index of Multiple Deprivation (SIMD) rank. The SIMD rank, demographics and severity of glaucoma at presentation were investigated using general linear modelling. RESULTS: There were 48 patients with severe glaucoma and 74 patients with non-severe glaucoma. In four, the severity could not be determined. Severity of glaucoma at presentation was significantly associated with SIMD rank, being most severe in patients from areas with the lowest ranks (p = 0.026). Age was a significant factor (p = 0.024), with severe glaucoma being more common in elderly patients. CONCLUSIONS: Age and socio-economic deprivation were associated with severity of glaucoma at presentation, with patients from areas of higher socio-economic deprivation presenting with more advanced glaucoma.
Asunto(s)
Glaucoma/epidemiología , Áreas de Pobreza , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Glaucoma/complicaciones , Glaucoma/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Escocia/epidemiología , Escotoma/epidemiología , Escotoma/etiología , Índice de Severidad de la Enfermedad , Factores Socioeconómicos , Trastornos de la Visión/epidemiología , Trastornos de la Visión/etiología , Trastornos de la Visión/fisiopatología , Campos VisualesRESUMEN
AIM: To establish the reliability, efficacy, and safety of disposable prism tonometry and validate its routine use for screening as well as monitoring of glaucoma. METHODOLOGY: Intraocular pressure (IOP) of 400 eyes of 200 consecutive patients who attended the general ophthalmic clinic was checked with both the Goldmann applanation tonometer and a disposable tonometer prism by an experienced examiner after obtaining informed consent. The data were statistically analysed. RESULTS: The mean difference in the IOP between the two types of prisms was 0.1 mmHg (SD+/-1 mmHg). CONCLUSION: Disposable prism tonometry provides a reliable, effective, and safe alternative to Goldmann reusable prism tonometry for routine screening as well as monitoring of glaucoma with the advantages of eliminating the need for chemical disinfection and therefore eliminating the risk of crossinfection.
Asunto(s)
Equipos Desechables , Glaucoma/diagnóstico , Tonometría Ocular/instrumentación , Infección Hospitalaria/prevención & control , Equipos Desechables/economía , Costos de Hospital , Humanos , Reproducibilidad de los Resultados , Tonometría Ocular/economía , Tonometría Ocular/métodos , Reino Unido , Selección Visual/instrumentación , Selección Visual/métodosRESUMEN
PURPOSE: To determine whether systemic diclofenac sodium affects the maintenance of mydriasis during phacoemulsification and to compare pupil diameter regression rates with those in a control group. SETTING: An ophthalmic unit of a National Health Service Trust Hospital in the United Kingdom. METHOD: A prospective, randomized control study of 100 patients presenting for cataract surgery was undertaken. Both groups were administered an identical mydriatic regime commencing 1 hour before surgery. In addition, the diclofenac group (n = 48) received 50 mg of oral diclofenac sodium 1 hour before surgery. Both the control (n = 52) and diclofenac groups had phacoemulsification by one experienced surgeon using a standard technique. The surgeon was masked as to which group the patient belonged. The irrigating fluid in all cases contained adrenaline. Pupil diameter was measured at five stages during surgery and recorded along with the times relative to the start of the procedure. RESULTS: Mean pupil diameter in the diclofenac group was slightly larger than in the control group, but the difference was not significant. Although mean pupil diameter at the start of surgery was 0.4 mm greater in the diclofenac group, the slopes of regression in pupil diameters were virtually identical between the first three stages of surgery, after which a slight reversal occurred in both groups. The slope of regression of mydriasis was small in both groups. CONCLUSION: Systemic diclofenac sodium 50 mg given orally 1 hour before surgery did not significantly inhibit miosis when compared with a control group. Regression rates of pupil mydriasis were small in both groups.
Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Inhibidores de la Ciclooxigenasa/administración & dosificación , Diclofenaco/administración & dosificación , Facoemulsificación , Pupila/efectos de los fármacos , Administración Oral , Anciano , Humanos , Midriáticos/administración & dosificación , Soluciones Oftálmicas , Estudios ProspectivosRESUMEN
PURPOSE: To identify the factors that most influenced patient choice of an excimer laser treatment center and those most likely to deter patients from selecting a particular center. SETTING: A National Health Service (NHS) excimer laser unit in the northeast of England. METHODS: An anonymous 24-item questionnaire was constructed. Each question had a visual analogue scale, anchored at each end with an adjectival description. Patients were asked to mark their response to the related question on the scale. Using the database of over 300 patients treated by excimer laser photorefractive keratectomy (PRK) at Sunderland Eye infirmary between May 1993 and December 1995, the first 140 consecutive patients were identified. Questionnaires were sent to them and returned between August 1 and October 31, 1995. RESULTS: A 64.3% reply rate (90 patients) was achieved. Overall, the results suggest that patients considered many factors to be important in their selection of a treatment center for PRK correction of myopia. Over 95% said that treatment and review by a consultant ophthalmologist, comprehensive follow-up appointments, professional attitude by staff, and reputation of the hospital were important factors in their selection of the center. Ninety to 95% said confidence in the clinical reputation and skills of the ophthalmic surgeons performing the treatment was important, as was having follow-up by only one or two staff members. Slightly more than 50% said that being treated in an NHS hospital setting (51.7%) or that expense of the treatment (50.5%) were important factors in their decision. CONCLUSION: Patients who chose to have excimer laser PRK based their choice of a unit on reputation of the staff and hospital but also on having care and follow-up by a consultant ophthalmic surgeon, high standards of equipment, continuity of care, and a comprehensive review system backed up by ready accessibility to staff members. Although proximity of a unit was important, cost appeared less important than the other factors.
Asunto(s)
Conducta de Elección , Córnea/cirugía , Miopía/cirugía , Satisfacción del Paciente , Queratectomía Fotorrefractiva , Adulto , Anciano , Femenino , Humanos , Láseres de Excímeros , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud , Queratectomía Fotorrefractiva/psicología , Refracción Ocular , Encuestas y Cuestionarios , Agudeza VisualRESUMEN
Metastatic uveal melanoma to the contralateral orbit is extremely rare, with only eight cases in the literature having been reported. We reviewed the clinical presentation, the histologic findings of the primary and secondary tumors, and the clinical outcome of these cases and studied an additional case of metastatic choroidal melanoma to the contralateral orbit that occurred 40 years after enucleation for the primary tumor. The long interval between recognition of the primary tumor and the appearance of clinically manifest metastatic disease in the contralateral orbit is the longest reported in the literature to date. The histologic features of the tumor cells of the enucleation specimen and those of the orbital metastasis were similar, consisting of spindle-cell type with minimal atypia. Combined use of immuno-phenotyping and electron microscopy substantiated the diagnosis of melanoma.