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Biomedical subjects

A D Dick

Publications and source records attributed to A D Dick.

At least 73 records · Page 4Linked to original sources

Ultrasonographic investigation of optic neuritis.

A pilot echographic study was conducted to determine the incidence and severity of optic nerve swelling in acute 'idiopathic' optic neuritis and to examine cerebrospinal fluid dynamics in the subarachnoid space, employing the method of standardised echography and the '30 degrees test'. An attempt was made to correlate the degree of nerve swelling with the initial visual loss and with the rate and extent of recovery of vision. The visual function and echographic features of the optic nerve in 27 patients with the diagnosis of acute optic neuritis were assessed with standardised echography. A significant increase in nerve diameter was found in 74% of cases. There was a correlation between nerve swelling and the severity of initial visual loss. The authors conclude that standardised echography is a useful tool in the diagnosis of optic neuritis and may play a role in predicting the visual outcome.

Adolescent↗

Herpes zoster chorioretinopathy.

Chorioretinitis and subsequent choroidal and retinal pigment epithelial atrophy following herpes zoster ophthalmicus (HZO) have rarely been reported. We report two patients, who several months following attacks of acute HZO, developed posterior fundus features of yellow, non-pigmented, punched-out areas of retinal pigment epithelial and choroidal pigment atrophy, which we have termed herpes zoster chorioretinopathy. An occlusive vasculitic process is proposed as the pathogenesis for this chorioretinopathy, and may be similar to that seen in the delayed cerebral vasculitis following HZO. A previous history of HZO should be sought in patients with a unilateral, multifocal, non-pigmented chorioretinopathy, as this may represent a characteristic delayed feature.

Aged↗

Flow cytometric identification of a minority population of MHC class II positive cells in the normal rat retina distinct from CD45lowCD11b/c+CD4low parenchymal microglia.

AIMS: This study aimed to isolate and classify by flow cytometry, the cell surface phenotype of microglia in the normal rat retina with a view to identifying putative antigen presenting cells (APC) within the retina, which has to date not been possible by immunohistochemistry. METHODS: Normal rat retinal microglia were isolated and classified using a modification of an isolation technique employing graduated Percoll density gradient cell separation and flow cytometric phenotypic criteria used for CNS microglia. RESULTS: Retinal microglia can be defined by flow cytometry on the basis of their CD45lowCD11b/c+CD4low cell surface expression. Constitutive MHC class II expression in the normal rat retina was confined almost exclusively to a very minor population of cells expressing neither low (microglia) nor high levels of CD45. Three colour flow cytometric analysis confirmed that these MHC class II positive cells were ED2+. CONCLUSIONS: Using this sensitive isolation technique we have identified the cell surface characteristics of ramified, resident microglia, and found that they do not constitutively express MHC class II. There is, however, constitutive MHC class II expression on a phenotypically distinct population of cells (CD45low/highED2+). We propose these cells are the counterpart of the perivascular macrophages found in the CNS which present antigen to extravasating T cells, although their exact retinal location can only be confirmed by immunohistochemical analysis. The role of parenchymal microglia as APC remains undefined. Future isolation of microglia and putative perivascular cells using this technique will help identify the role these cells play in the initiation and perpetuation of immune responses within the retina.

Animals↗

Immunomodulation of experimental autoimmune uveoretinitis: a model of tolerance induction with retinal antigens.

Experimental autoimmune uveoretinitis (EAU) is a CD4+ T-lymphocyte mediated inflammation of the uveal tract and retina. As a model of human posterior uveitis it permits further understanding of the underlying immunopathogenesis of uveitis. It also allows for preclinical trials of immunosuppressive therapies and in vivo assessment of alternative strategies for immunointervention. This review highlights possible immunostrategic modalities which prevent the initiation or perpetuation of the immune response, and in particular reports on the novel effect of intranasal induction of tolerance with retinal antigens, prior to immunisation with retinal antigens. The mechanisms and potential application of this 'natural' method of immunosuppression in the treatment of autoimmune disease are discussed.

Adjuvants, Immunologic↗

Intranasal administration of retinal antigens suppresses retinal antigen-induced experimental autoimmune uveoretinitis.

Bovine retinal extract (RE) is a heterologous mixture of highly uveitogenic proteins including S-Antigen (S-Ag), interphotoreceptor retinol binding protein (IRBP) and rhodopsin, and is a potent inducer of experimental autoimmune uveoretinitis (EAU). Intranasal inoculation of Lewis rats with RE performed daily for 10 days prior to immunization with RE suppresses both the severity and the incidence of the clinical response and histopathological changes in EAU. Significant suppression of the disease in treated animals could be achieved with a total (cumulative) intranasal inoculum of 42 micrograms of antigen. Animals which were treated with extract exhibited a normal total antibody response to S-Ag, IRBP and retinal extract when compared with controls [phosphate-buffered saline (PBS) treated] animals. The antibody response in tolerized animals was predominantly anti-S-Ag IgG2a with suppression of anti-S-Ag IgM response. Treated animals had a significantly suppressed delayed-type hypersensitivity (DTH) response to retinal extract but normal response to purified protein derivative (PPD) compared to control animals. Adoptive transfer of splenocytes from treated animals also demonstrated some protection against RE-induced EAU. These results demonstrate that tolerance induction impairs the onset and severity of EAU by inhibiting the DTH response to heterologous mixture of retinal antigens.

Administration, Intranasal↗

A spectrum of clinical signs in anterior uveitis.

The range of clinical changes that occur in posterior uveitis have been well documented. We describe two clinical features of anterior uveitis which we have termed 'iris pigment epithelitis' and 'iris vasculitis'. Other clinical forms of iritis also exist and together with our described findings parallel the spectrum of clinical presentations in posterior uveitis.

Adult↗

Clinical experience with interferon alfa-2a for exudative age-related macular degeneration.

There has been recent interest in the use of systemic interferon alfa-2a treatment for choroidal neovascular membranes (CNV). Here a pilot study is reported in which 10 patients with exudative age-related macular degeneration (ARMD) have been treated with a course of interferon injections. Of nine eyes with CNV there has been clinical and angiographic improvement in one eye and maintenance of visual acuity at pretreatment levels in three eyes (mean follow up period 7.6 months). Clinical appearance in five eyes was unchanged but these eyes still had active CNV. Two eyes with pigment epithelial detachment showed no clinical or angiographic change after interferon therapy although visual acuity in one eye had improved. Interferon alfa-2a may have a role to play in the treatment of ARMD as an adjunct to laser photocoagulation.

Aged↗

Nasal administration of retinal antigens suppresses the inflammatory response in experimental allergic uveoretinitis. A preliminary report of intranasal induction of tolerance with retinal antigens.

Current immunotherapy of posterior uveitis is non-specific and limited by drug toxicity and unpredictable relapses on therapy. Alternative modes of therapy being investigated using the rat model of experimental autoimmune uveoretinitis (EAU) have included the induction of tolerance with oral administration of milligram quantities of retinal antigens. In this preliminary report we demonstrate that tolerance to retinal antigens can be induced via the upper respiratory tract with microgram doses of antigen, preventing subsequent induction of EAU.

Animals↗

Standardised echography in the differential diagnosis of extraocular muscle enlargement.

Standardised echography is well documented for its use in the evaluation of enlarged extraocular muscles in orbital disease, but is still a largely underdeveloped imaging method in Britain. This paper demonstrates the technique of muscle ultrasound scanning and the characteristic echographic findings in a variety of extraocular muscle diseases, as illustrated by five case reports. The role of echography in the management of such cases is discussed.

Aged↗

Immunocytochemical analysis of blood lymphocytes in uveitis.

We studied the surface expression of activation markers IL2-R, HLA-DR and CD45-RO on peripheral T-lymphocytes in two groups of patients (n = 26) with idiopathic uveoretinitis, compared with controls. Thirteen patients were analysed by alkaline phosphatase anti-alkaline phosphatase (APAAP) immunocytochemistry, which demonstrated a significant rise in expression of HLA-DR and IL2-R surface markers. Flow cytometric analysis was performed on a further 13 patients, which confirmed a significant rise in IL2-R expression in uveitis patients. Within this group systemic activation was confined to patients with idiopathic retinal vasculitis. Dual flow cytometry confirmed a CD4+,IL2--R+ T--lymphocyte phenotype. A further 4 patients with retinal vasculitis who had been treated with cyclosporin A demonstrated a 32% reduction in IL2-R expression over a 3-month period. Analysis of CD45-RO and CD5+ cells was found to be uninformative in this study. We have demonstrated activated peripheral lymphocytes in patients predominantly with retinal vasculitis, the significance of which is discussed.

Biomarkers↗

The use of lithium clearance studies in the early detection of cyclosporin A (CsA) nephrotoxicity: a protocol of renal function assessment with CsA therapy.

Cyclosporin A nephrotoxicity was studied with the use of lithium and creatinine clearance tests in 18 patients with chronic intraocular inflammation (duration of treatment 3-48 months). In 11 patients lithium clearance and fractional excretion of lithium were significantly reduced (compared with pretreatment levels) within the first six months of treatment. There was no significant change in either serum creatinine or creatinine clearance within this period. In 14/18 patients there was a significant reduction in lithium clearance and fractional excretion of lithium during the treatment period. 7 patients whose therapy was stopped because of continuing nephrotoxicity despite dose reduction, demonstrated some reversibility of renal function on cessation of cyclosporin A. We propose a protocol for the assessment of renal function in these patients so that with dose modulation the changes in these parameters can be minimised, reducing the risk of renal impairment, whilst maximising immunosuppressive treatment.

Chronic Disease↗

Brainstem vascular accidents and cranial arteritis.

Cranial Arteritis (Giant Cell Arteritis) is a clinical diagnosis supported by a raised erythrocyte sedimentation rate (ESR) and if required confirmed by a temporal artery biopsy. This case reports on an unusual presentation where a delay in the diagnosis resulted in visual impairment, illustrating the need for awareness of diagnosis in acute strokes in the elderly.

Aged↗

A case of sinusitis presenting with spheno-cavernous syndrome: discussion of the differential diagnosis.

A 60 year old gentleman presented with a left spheno-cavernous syndrome resulting in impaired ocular motility, proptosis and visual loss in an otherwise clinically quiet eye. The history led to a clinical suspicion of posterior ethmoiditis, which was confirmed on C.T. scanning. Surgical drainage and antibiotic treatment resolved the symptoms, but visual impairment persisted. The differential diagnosis and management of spheno-cavernous syndrome is discussed in context with this atypical presentation of orbital cellulitis.

Combined Modality Therapy↗