NCT00487253.

No abstract

BackgroundThe inflammatory response is prominent in the pathogenesis of dermal leishmaniasis. We hypothesized that regulatory T cells (Tregs) may be diminished in chronic dermal leishmaniasis (CDL) and contribute to healing during treatment.Methodology/Principal FindingsThe frequency and functional capacity of Tregs were evaluated at diagnosis and following treatment of CDL patients having lesions of ≥6 months duration and asymptomatically infected residents of endemic foci. The frequency of CD4+CD25hi cells expressing Foxp3 or GITR or lacking expression of CD127 in peripheral blood was determined by flow cytometry. The capacity of CD4+CD25+ cells to inhibit Leishmania-specific responses was determined by co-culture with effector CD4+CD25− cells. The expression of FOXP3, IFNG, IL10 and IDO was determined in lesion and leishmanin skin test site biopsies by qRT-PCR. Although CDL patients presented higher frequency of CD4+CD25hiFoxp3+ cells in peripheral blood and higher expression of FOXP3 at leishmanin skin test sites, their CD4+CD25+ cells were significantly less capable of suppressing antigen specific-IFN-γ secretion by effector cells compared with asymptomatically infected individuals. At the end of treatment, both the frequency of CD4+CD25hiCD127− cells and their capacity to inhibit proliferation and IFN-γ secretion increased and coincided with healing of cutaneous lesions. IDO was downregulated during healing of lesions and its expression was positively correlated with IFNG but not FOXP3.Conclusions/SignificanceThe disparity between CD25hiFoxp3+ CD4 T cell frequency in peripheral blood, Foxp3 expression at the site of cutaneous responses to leishmanin, and suppressive capacity provides evidence of impaired Treg function in the pathogenesis of CDL. Moreover, the concurrence of increased Leishmania-specific suppressive capacity with induction of a CD25hiCD127− subset of CD4 T cells during healing supports the participation of Tregs in the resolution of chronic dermal lesions. Treg subsets may therefore be relevant in designing immunotherapeutic strategies for recalcitrant dermal leishmaniasis caused by Leishmania (Viannia) species.

Purpose. To establish which reference body offers the greatest sensitivity in keratoconus (KC) diagnosis, obtain normative data for the myopic population with toric ellipsoid reference bodies, and determine the cutoff points for a population with KC.Methods. A retrospective, observational study of the entire Scheimpflug tomographer database of the Fundación Jiménez Díaz in Madrid was conducted to identify a normal myopic and a KC myopic population. Three different reference bodies were tested on all patients: best fit sphere (BFS), best fit toric ellipsoid with fixed eccentricity (BFTEFE), and best fit toric ellipsoid (BFTE). Anterior and posterior elevation measurements at the apex and thinnest point were recorded, as well as the root mean square of posterior elevations (RMS-P). Normative data were extracted, and receiver operating characteristic (ROC) curves were generated to obtain cutoff points between the normal and KC population.Results. A total of 301 eyes were included, comprising 219 normal myopic and 82 myopic KC eyes. BFS and BFTEFE produced the best results when measuring posterior elevation at the thinnest point. BFTE had better sensitivity with the RMS-P. From all measurements, best sensitivity (100%) was achieved with a cutoff point of 8 μm of posterior elevation at the thinnest point using the BFTEFE. BFTE was found to hide the cone in certain patients.Conclusions. Posterior elevation measured at the thinnest point with a BFTEFE is the best-performing parameter and, therefore, is recommended to discriminate between normal and KC patients within a myopic population.

Abstract. For over 60 years, pentavalent antimony (Sb v