ABSTRACT.Purpose: Clinical evidence of retinal pigment epithelium (RPE) alterations after intra-arterial (IAC) and intravitreal chemotherapy (IViC) of retinoblastoma has been reported. We, therefore, investigated the cellular toxic effects of melphalan, topotecan and carboplatin on the RPE in a cell culture model. Methods: The effects of melphalan, carboplatin and topotecan on ARPE19 cell morphology were examined by phase contrast microscopy. Cell proliferation was quantified by BrdU incorporation, cell viability studied via MTS assays, and cell densities were estimated by Crystal Violet staining, and apoptosis induction studied via caspase 3/7-activity assays after a 24-hr incubation period. Staurosporine, media without fetal bovine serum, diluents of melphalan, carboplatin and topotecan were applied as positive and negative controls, respectively. Results: We observed a concentration-dependent increase in the number and size of gaps in the ARPE19 cell layer with each drug. There was a significant decrease in proliferative activity and cell viability of RPE cells as well as an increase in apoptosis after 24 hrs culture in media supplemented with melphalan and topotecan. Carboplatin had comparable effects on cell proliferation and cell viability; however, no significant apoptotic impacts were observed. The three cytostatic drugs had insignificant effects on cell density measurements. Conclusions: Morphological monitoring and toxicity assays indicate a direct toxic effect of melphalan and the other two cytostatic drugs on ARPE19 cells. Thus, a direct toxic effect of melphalan in vivo after IAC or IViC on the RPE seems probable and may explain the clinical and angiographic RPE alterations observed in some retinoblastoma patients.

A 63-year-old woman presented with a history of increasing dysphagia of about two weeks duration. Laryngoscopy revealed a nonulcerated supraglottic epitheliomatous lesion that morphologically appeared well-differentiated and distinctly oncocytoid. Although the tumour lacked any criteria for malignancy such as cellular atypia, pleomorphism or necroses, it recurred twice after primary surgery and later gave rise to multiple painful skin metastases. The diagnosis of an oncocytoid differentiated neuroendocrine carcinoma of the larynx (laryngeal carcinoid) was made. Misinterpretation of laryngeal carcinoids is common, but can be avoided if one is familiar with this rare variant of laryngeal neoplasms

Purpose: The primary endpoint results from the comparing alternative ranibizumab dosages for safety and efficacy in retinopathy of prematurity (CARE-ROP) core study identified ranibizumab as an effective treatment to control acute retinopathy of prematurity (ROP). This study reports the 1-and 2-year follow-up data focusing on long-term functional outcomes and safety. Methods:The CARE-ROP trial compared 0.12 mg versus 0.20 mg ranibizumab in 20 infants with ROP in a multicentric, prospective, randomized, double-blind, controlled study design. Sixteen patients entered the follow-up period. An ophthalmologic assessment at one year postbaseline was acquired from all 16 patients and a neurodevelopmental assessment at two years postbaseline was acquired from 15 patients.Results: Fifteen of 16 infants were able to fixate and follow moving objects at one year postbaseline treatment. One child progressed to stage 5 ROP bilaterally between the end of the core study and the 1-year follow-up (first seen at PMA 75 weeks). Mean spherical equivalents were À1.9 diopters (D) and À0.75 D in the 0.12 mg and the 0.20 mg treatment arms. Strabismus was present in seven and nystagmus in five out of 16 infants. Mental development scores were within normal limits in six out of ten patients with available data. No statistically significant difference was observed between the two treatment arms. Conclusion:Neurodevelopmental and functional ocular outcomes 1 and 2 years after treatment with ranibizumab are reassuring regarding long-term safety. Late reactivation of ROP, however, represents a challenge during the follow-up phase and it is of utmost importance that regular follow-ups are maintained.

In the context of the shift toward clean, carbon-free energy, hydrogen (H2) has received growing attention as an energy carrier. We monitored a simulated leakage of gaseous molecular H2, e.g., from a pipeline. H2 was injected into a shallow aquifer, and the resulting biogeochemical processes were monitored. For the first time, stable isotopes of hydrogen were used to track in situ H2 transport and consumption. Isotopic composition of injected H2 was δ2H = −161.1 ± 0.4‰. During the injection, initial shifts in the isotope signature of about Δ2H = +8‰ in well D06 (1 m from injection) and Δ2H = −120‰ in well D04 (2 m from injection) were observed, probably caused by a mass-dependent isotope effect associated with the pressure of the injection and the migration of the gas phase through pores and channels in the aquifer. After the injection, H2 concentrations decreased and an equilibrium isotope exchange with water led to an isotopic depletion of H2 (δ2H = −710.7 ± 2.7‰) within 28 days, presumably catalyzed by hydrogenase enzymes of microbes. The theoretical equilibrium between H2 and water was however not reached. We hypothesize that a continuous isotopic shift in available H2 as a result of physical transport processes resulted in a new isotope equilibrium with water, catalyzed by hydrogenases. Acetate detected in groundwater samples indicates in situ H2 oxidation by microbial homoacetogenesis. In laboratory experiments using H2-amended sediments sampled from the same site, microbial H2 oxidation was accompanied by equilibrium isotope exchange with water and homoacetogenesis and ferric iron reduction were the main microbial H2-consuming processes. Overall, the H2 isotope ratio was considerably impacted by physical and microbial processes occurring in the shallow aquifer. Monitoring of the equilibrium isotope exchange between H2 and water could be used as a proxy for ongoing microbial H2 oxidation.

No abstract