Sirolimus and mycophenolate as combination prophylaxis in corneal transplant recipients at high rejection risk.

PURPOSE: To examine efficacy and safety of dual sirolimus and mycophenolate mofetil systemic immunosuppression as allograft rejection prophylaxis after penetrating keratoplasty in patients at high rejection risk. DESIGN: Prospective, interventional case series. METHODS: settings: Single-center subspecialty clinic. patients: Six penetrating transplant recipients at high rejection risk and with no confounding additional cause for high risk of graft failure. All transplant recipient eyes had good visual potential. intervention: Treatment with oral mycophenolate mofetil in combination with sirolimus for 1 year, and sirolimus alone for 2 further years after keratoplasty at doses used in prophylaxis after cadaveric kidney transplantation. main outcomes measures: Interval to first rejection episode, transplant survival, and significant drug adverse effects. Minimum follow-up interval was 13 months after transplantation. RESULTS: Rejection episodes occurred in 3 patients, one of which led to transplant failure. Of the 6 transplants, 5 remained clear at latest follow-up. Hepatotoxicity required discontinuation of mycophenolate in 1 patient, and both drugs were otherwise free of significant adverse effects. CONCLUSIONS: Sirolimus and mycophenolate mofetil in combination are effective in extending corneal transplant survival in most but not all high rejection risk patients and generally are well tolerated. Results justify further evaluation of this regimen in a larger controlled study.

Outbreak of contact lens-related Fusarium keratitis in France.

BACKGROUND/AIMS: In the context of a recent series of Fusarium keratitis cases in Singapore and the United States, we describe an outbreak of fungal keratitis attributable to Fusarium species among contact lens wearers in France. METHODS: Hospital-based case series. All cases of Fusarium keratitis diagnosed in Department of Ophthalmology of the Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts in Paris were reviewed from January 2004 through November 2006. A standardized telephone interview was conducted to obtain additional clinical information for research and the analysis of risk factors. RESULTS: During the study period, 17 patients (18 affected eyes) were diagnosed with Fusarium keratitis. The vast majority (14 patients, 82%) wore contact lenses. Six patients (43% of contact lens wearers) reported using ReNu with MoistureLoc. Eight patients reported using others brands of contact lens cleaning solution. The final best corrected visual acuity ranged from 20/20 to light perception; 5 patients (29.5%) required emergency therapeutic or tectonic corneal transplantation. No specific differences including Fusarium species or severity of keratitis were found between keratitis with ReNu MoistureLoc and keratitis without ReNu MoistureLoc. CONCLUSIONS: This series reports the first outbreak of Fusarium keratitis in Europe. Once again, ReNu with MoistureLoc, a multipurpose lens disinfecting solutions seems to be related with Fusarium keratitis.

Structural localization and expression of CXCL12 and CXCR4 in rat heart and isolated cardiac myocytes.

CXCL12 (SDF-1), which binds CXCR4, is involved in several physiological and pathophysiological processes. In heart, this axis seems to play a key role in cardiogenesis and is involved in the neovascularization of ischemic tissues. Rats have three known CXCL12 mRNA isoforms, of which only alpha and gamma are present in the normal heart. However, little is known about CXCL12 protein expression and localization. We investigated the pattern of protein expression and the localization of both CXCR4 and CXCL12 in the heart, using isolated cardiomyocytes and a rat myocardial infarction model. Western blots showed that cardiomyocytes contained a specific 67-kDa CXCR4 isoform and a 12-kDa CXCL12 isoform. Confocal and electron microscopy clearly showed that CXCR4 was present at the plasmalemma and CXCL12 in continuity of the Z-line, in the proximal part of T-tubules. In conclusion, we provide the first description of the expression and fine localization of CXCR4 and CXCL12 proteins in normal rat heart and cardiomyocytes. These results suggest that the CXCL12/CXCR4 axis may be involved in cardiomyocyte calcium homeostasis regulation. Our work and the well-known chemoattraction properties of the CXCL12/CXCR4 axis highlight the importance of deciphering the function of this axis in both normal and pathological hearts.