Oxygen saturation measurements of the retinal vasculature in treated asymmetrical primary open-angle glaucoma using hyperspectral imaging.

PURPOSE: To determine whether there are differences in retinal vascular oxygen saturation measurements, estimated using a hyperspectral fundus camera, between normal eyes and treated eyes of subjects with asymmetrical primary open-angle glaucoma (POAG). METHODS: A noninvasive hyperspectral fundus camera was used to acquire spectral images of the retina at wavelengths between 556 and 650 nm in 2-nm increments. In total, 14 normal eyes and both eyes of 11 treated POAG subjects were imaged and analyzed using algorithms that use the spectral variation of the optical densities of blood vessels to estimate the oxygen saturation of blood within the retinal vasculature. In the treated POAG group, each of the eyes were categorized, based on the mean deviation of the Humphrey visual-field analyzer result, as either more-advanced or less-advanced, glaucomatous eyes. Unpaired t-tests (two-tailed) with Welch's correction were used to compare the mean oxygen saturation between the normal subjects and the treated POAG subgroups. RESULTS: In less-advanced and more-advanced-treated POAG eyes, mean retinal venular oxygen saturations (48.2±21.6% and 42.6±18.8%, respectively) were significantly higher than in normal eyes (27.9±9.9%; P=0.03 and 0.01, respectively). Arteriolar oxygen saturation was not significantly different between normal eyes and treated POAG eyes. CONCLUSIONS: The increased oxygen saturation of the retinal venules in advanced-treated POAG eyes may indicate reduced metabolic consumption of oxygen in the inner retinal tissues.

Human de novo papillary renal-cell carcinomas in a kidney graft: evidence of recipient origin with adenoma-carcinoma sequence.

Papillary renal-cell carcinoma (pRCC) is unusual for its occurrence in kidneys with chronic dysfunction, for its frequent multifocality and for its common association with papillary adenoma, a benign renal lesion morphologically indistinguishable from pRCC. Concomitant development of papillary adenoma and pRCC in five transplanted kidneys, where donor and recipient characteristics are well established, provided a unique opportunity for molecular studies of de novo pRCC carcinogenesis. We aimed to study this tumor type to determine whether or not the different papillary tumors have the same origin, and whether or not papillary adenomas are precursor lesions of pRCC. We performed XY-FISH in sex-mismatched kidney transplants, and polymorphic microsatellite DNA and high-resolution melting of mitochondrial DNA analyzes in all five patients on laser-microdissected tumor cells, then compared these molecular profiles to donor and recipient profiles. This study (i) identified the recipient origin of de novo papillary adenomas and pRCCs in a kidney transplant, (ii) demonstrated an identical origin for precursor cells of papillary adenomas and pRCCs and (iii) showed additional genetic alterations in pRCCs compared to papillary adenomas. This molecular approach of papillary tumors developed in transplanted kidney identified successive steps in carcinogenesis of human de novo papillary renal-cell carcinoma.

Spectral imaging of the retina.

INTRODUCTION: The work described here involved the use of a modified fundus camera to obtain sequential hyperspectral images of the retina in 14 normal volunteers and in 1 illustrative patient with a retinal vascular occlusion. METHODS: The paper describes analysis techniques, which allow oximetry within retinal vessels; these results are presented as retinal oximetry maps. RESULTS: Using spectral images, with wavelengths between 556 and 650 nm, the mean oxygen saturation (OS) value in temporal retinal arterioles in normal volunteers was 104.3 (± 16.7), and in normal temporal retinal venules was 34.8 (± 17.8). These values are comparable to those quoted in the literature, although, the venular saturations are slightly lower than those values found by other authors; explanations are offered for these differences. DISCUSSION: The described imaging and analysis techniques produce a clinically useful map of retinal oximetric values. The results from normal volunteers and from one illustrative patient are presented. Further developments, including the recent development of a 'snapshot' spectral camera, promises enhanced non-invasive retinal vessel oximetry mapping.

Management of metabolic cytochrome P450 3A4 drug-drug interaction between everolimus and azole antifungals in a renal transplant patient.

We report a case of a 54-year-old male renal transplant patient who received antifungal azole treatment in combination with the recently introduced immunosuppressant agent everolimus to prevent post-transplantation aspergillosis reactivation. Voriconazole was withdrawn after 1 month because of elevated concentrations (5 mg/L trough plasma determination) and hepatotoxicity, and substituted by several months of treatment with posaconazole (observed concentration range 1-2 mg/L). We observed pharmacokinetic drug interactions between both voriconazole and posaconazole, and everolimus cytochrome P450 3A4 metabolism, resulting in 7.5- and 3.8-fold increase, respectively, in everolimus blood trough concentrations. Combined therapeutic drug monitoring (TDM) of both everolimus and azole inhibitors allowed for safe and convenient modification of everolimus dosage, which was tapered to maintain a target range of 5-15 ng/mL during and after antifungal treatments. While significant in their effects, these drug interactions were able to be managed safely through a careful approach to management and use of individual TDM.