Juvenile cataract in association with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by benign hamartomas occurring in multiple organ systems including the brain, kidneys, heart, lungs, liver, skin, and the eyes. Typical retinal findings associated with TSC include astrocytic hamartoma and achromic patch. While rare cases of cataract occurring in the setting of TSC have been reported, this is the first analysis of a large series of individuals with TSC that aims to quantify the frequency of this finding and to describe its clinical and genetic associations. MATERIALS AND METHODS: This is a retrospective chart review of 244 patients from the Herscot Center for Tuberous Sclerosis Complex at the Massachusetts General Hospital who underwent complete ophthalmic examination. We describe the clinical and genetic findings in five individuals with TSC and juvenile cataract. RESULTS: Four of five cases (80%) were unilateral. The cataract was described as having an anterior subcapsular component in 3 of 5 cases (60%). Three individuals (60%) underwent lensectomy with intraocular lens (IOL) implant and two individuals (40%) were observed. Genetic testing revealed a known disease-causing mutation in TSC2 in 100% of cases. CONCLUSIONS: Recent evidence suggests that mTOR signaling may play a role in cataract formation which could explain the relatively high incidence of juvenile cataract in this population. Juvenile cataract is a potentially under-recognized ocular manifestation of TSC.

EGFR fluorescence in situ hybridisation assay: guidelines for application to non-small-cell lung cancer.

There is a need for predictive biomarkers that identify non-small-cell lung cancer (NSCLC) patients most likely to respond to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. There are numerous potential candidates, although none has been proven in prospective clinical trials. The EGFR gene copy number evaluated by fluorescence in situ hybridisation (FISH) has been highlighted as one of the most effective markers for sensitivity to EGFR TKIs in large phase III, randomised placebo-controlled trials and has been used in clinical settings to assist physicians in defining the therapeutic regimen. The EGFR FISH assay has technical challenges and it is critical that detailed guidelines are provided to help clinical laboratories in performing and interpreting the test. Excellent assay reproducibility and portability rates among laboratories are crucial to guarantee that accurate clinical decisions can be made for patients with NSCLC. This article discusses the consensus outcomes of a global workshop convened to discuss key technical issues and standardise reading strategies for the EGFR FISH assay of NSCLC tumour tissue.

A homologous in vitro model to study interactions between alphaherpesviruses and trigeminal ganglion neurons.

A key aspect in the life cycle of alphaherpesviruses is their neurotropic behaviour. Sensory neurons of the trigeminal ganglion (TG) are important target cells for many alphaherpesviruses (including herpes simplex virus 1, pseudorabies virus (PRV), bovine herpesvirus 1) and constitute major sites for latent infections. The aim of this study was to develop an in vitro model that simulates the in vivo infection pattern of TG neurons by alphaherpesviruses. To this end, we developed a homologous in vitro two-chamber model using PRV and porcine TG neurons. TG of 4- to 6-week-old piglets were dissociated and cultured in the inner chamber of the in vitro model, which is separated from the outer chamber by a medium- and virus-impermeable silicon barrier. Outgrowth of axons from neuronal cell bodies in the inner chamber through the silicon barrier into the outer chamber could be observed after 2-3 weeks of cultivation. Subsequent addition of PRV to the outer chamber resulted in exclusive infection of the TG neurons by transport of virus through the axons, subsequently giving rise to productively infected TG neurons that transmitted virus to contacting neurons and non-neuronal cells in the inner chamber. Thus, we established a homologous in vitro model that mimics the natural route of alphaherpesvirus infection of TG neurons that can be used to study interactions between these viruses and this pathogenetically very important cell type.