A sore red eye with systemic involvement

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Clinical and molecular features associated with cystic visceral lesions in von hippel-lindau disease.

Von Hippel-Lindau (VHL) is an uncommon oncogenic disorder which occurs as a result of genetic mutations on chromosome 3p. Retinal capillary haemangiomas and CNS haemangioblastomas have been well-characterised in genotypic-phenotypic analyses, but cystic visceral lesions are less common and have been less frequently studied. The aim of this study was to perform genotypic and phenotypic analysis of a cohort of VHL patients that developed cystic visceral lesions to determine whether their genotype differs from that seen in other manifestations of VHL and whether the ocular manifestations differ.This study reports a prospective case series of twenty-one patients identified from the Hammersmith Hospital Genetics Service database as having VHL mutations. Patients underwent regular ocular and systemic screening as well as genotypic analysis. The main outcome measures were the development of VHL lesions, either ocular or systemic.Cystic visceral lesions were detected in six of the 21 patients from the clinic (29%). These included renal cysts in four patients, pancreatic cysts in three patients, and an epididymal cystadenoma in one patient. Renal cysts were not associated with any specific genotype. Pancreatic cysts appeared to occur in association with VHL gene deletions and all developed CNS haemangioblastomas. Only one patient developed ocular manifestations, which occurred in this patient in the form of two retinal capillary haemangiomas.VHL gene deletions appeared to be associated with pancreatic cysts and the development of CNS haemangioblastomas. Ocular manifestations are uncommon in this group of patients

Ocular Syphilis

Syphilis is still an important cause of eye disease and blindness in the Western world and is being diagnosed with increasing frequency in patients with HIV/AIDS. It is known as the 'great imitator' and can present to ophthalmologists with myriad symptoms and signs. Diagnosis is based on clinical examination and serological testing. The mainstay of treatment remains penicillin, but care needs to be taken that the treatment given is adequate for neurosyphilis

Multifocal Choroiditis

Multifocal choroiditis forms a subset of the white-dot syndromes in which inflammation is focussed on the choroid. Multifocal choroiditis with panuveitis (MCP), punctate inner choroidopathy (PIC) and birdshot chorioretinopathy (BCR) have been distinguished, although some consider PIC to be a variant of MCP. The aetiology is largely unknown and treatment is with local or systemic corticosteroids as well as immunosuppressive agents. Visual prognosis depends on the adverse effects of uveitis

The P2X7 receptor in immune cells

The P2X7 receptor is a cation channel activated by high concentrations of ATP. Its stimulation is pro-inflammatory, with activation resulting in the release of cytokines (notably IL-1β), changes in plasma membrane lipid distribution, and cell death. A central role for P2X7 in IL-1β secretion via the NALP3 inflammasome has been confirmed in gene-deficient mice generated by GlaxoSmithKline (GSK) and Pfizer. It is abundantly expressed on cells of the immune system and may play a role in the pathogenesis of autoimmune disease, notable systemic lupus erythematosus (SLE). Indeed, P2X7 has become an important potential therapeutic target, and antagonists are currently in Phase II clinical trials for treatment of rheumatoid arthritis and chronic obstructive pulmonary disease. In this thesis, I describe my investigation into the role of the P2X7 receptor in immune function, examining in detail the responses of murine T cells, macrophages and dendritic cells to P2X7 stimulation. Investigation of T cell responses reveals a novel form of cell death in which cells initially shrink and then swell, before undergoing catastrophic lysis with release of cellular contents into the surrounding milieu, a process which I have termed aponecrosis as it bears features of both apoptosis and necrosis. In addition, I report a detailed characterisation of immune cells from the GSK P2X7-/- mouse. Functional and mRNA data demonstrate tissue-specific ‘leakiness’, such that P2X7 expression is ablated in P2X7-/- macrophages, but not in P2X7-/- T cells. This explains previous paradoxical experimental and immunohistochemical data achieved with P2X7-/- mice without the need to invoke the expression of an additional P2X7-like protein cross-reactive with P2X7 antibodies. Finally, I report the use of a mouse model of antibody-mediated glomerulonephritis to demonstrate that P2X7 plays a key pro-inflammatory role in immune-mediated injury and that this receptor is a possible therapeutic target in vivo

Ocular Syphilis

Syphilis is still an important cause of eye disease and blindness in the Western world and is being diagnosed with increasing frequency in patients with HIV/AIDS. It is known as the 'great imitator' and can present to ophthalmologists with myriad symptoms and signs. Diagnosis is based on clinical examination and serological testing. The mainstay of treatment remains penicillin, but care needs to be taken that the treatment given is adequate for neurosyphilis