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Staropoli J.F.,Massachusetts General Hospital | Haliw L.,Massachusetts General Hospital | Biswas S.,Massachusetts General Hospital | Garrett L.,Helmholtz Center Munich | And 44 more authors.
PLoS ONE | Year: 2012

Cln3Δex7/8 mice harbor the most common genetic defect causing juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive disease involving seizures, visual, motor and cognitive decline, and premature death. Here, to more thoroughly investigate the manifestations of the common JNCL mutation, we performed a broad phenotyping study of Cln3Δex7/8 mice. Homozygous Cln3Δex7/8 mice, congenic on a C57BL/6N background, displayed subtle deficits in sensory and motor tasks at 10-14 weeks of age. Homozygous Cln3Δex7/8 mice also displayed electroretinographic changes reflecting cone function deficits past 5 months of age and a progressive decline of retinal post-receptoral function. Metabolic analysis revealed increases in rectal body temperature and minimum oxygen consumption in 12-13 week old homozygous Cln3Δex7/8mice, which were also seen to a lesser extent in heterozygous Cln3Δex7/8 mice. Heart weight was slightly increased at 20 weeks of age, but no significant differences were observed in cardiac function in young adults. In a comprehensive blood analysis at 15-16 weeks of age, serum ferritin concentrations, mean corpuscular volume of red blood cells (MCV), and reticulocyte counts were reproducibly increased in homozygous Cln3Δex7/8 mice, and male homozygotes had a relative T-cell deficiency, suggesting alterations in hematopoiesis. Finally, consistent with findings in JNCL patients, vacuolated peripheral blood lymphocytes were observed in homozygous Cln3Δex7/8 neonates, and to a greater extent in older animals. Early onset, severe vacuolation in clear cells of the epididymis of male homozygous Cln3Δex7/8 mice was also observed. These data highlight additional organ systems in which to study CLN3 function, and early phenotypes have been established in homozygous Cln3Δex7/8 mice that merit further study for JNCL biomarker development. © 2012 Staropoli et al.

Wachtlin J.,Augenabteilung Sankt Gertrauden Krankenhaus | Ringwald A.,Augenklinik Klinikum Dortmund | Maulhardt T.,Facharzt fur Augenheilkunde | Pohl K.,Novartis | Wiedon A.,Novartis
Graefe's Archive for Clinical and Experimental Ophthalmology | Year: 2015

Purpose: In the non-interventional ophthalmological study ‘BRIDGE’ the routine care of patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab was observed in Germany. A patient regularly sees the general ophthalmologist (GO) for monitoring and, if needed, the injecting ophthalmologist (IO) for intravitreal injections (IVI). Thus, patients are routinely treated by two ophthalmologists in parallel and patient care depends on their collaboration. This cooperation was evaluated based on network questionnaires. Methods: ‘BRIDGE’ was a multicenter, national, open-label, prospective, observational study, conducted between July 2010 and December 2012. The network questionnaire for GOs consisted of 51 questions, while the similar questionnaire for IOs consisted of 43 questions, addressing the type and details of the individual collaboration. The statistical analysis was purely descriptive. Results: The network questionnaire for GOs was completed by 152 GOs, regularly cooperating with 2.5 ± 1.1 IOs, while the questionnaire for IOs was completed by 43 IOs, regularly cooperating with 23.2 ± 23.6 GOs. Generally, both GOs and IOs stated that they regularly exchange information regarding the patients’ situation. Diagnostic standards were only established for 15 % of the GOs’ collaborations and for 35 % of the IOs’ collaborations. After initial treatment, both GOs and IOs agreed on the medical significance of regular monitoring visits performed by the GOs. Agreements on re-treatment criteria were only established in the case of 16 % of the GOs and 28 % of the IOs. Overall, both GOs and IOs were satisfied with the current situation, with regard to the medical treatment situation for patients and to the cooperation within the networks. Conclusions: The network questionnaires revealed well-established cooperation between IOs and GOs in Germany with an accepted division of responsibilities for the routine care of patients with nAMD. However, the cooperation between two ophthalmologists treating one patient harbors risks. Agreements on diagnostic and re-treatment criteria would help to improve network performance and outcomes. © 2015 Springer-Verlag Berlin Heidelberg

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