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S Lightman

Publications and source records attributed to S Lightman.

At least 73 records · Page 4Linked to original sources
PubMed1998

Effects of drug therapy on Toxoplasma cysts in an animal model of acute and chronic disease.

PURPOSE: To evaluate the effects of drug therapy on the clinical course of acute acquired Toxoplasma retinochoroiditis and on the number of Toxoplasma cysts present in the brain and ocular tissues in the hamster animal model. METHODS: The Syrian golden hamster animal model of Toxoplasma retinochoroiditis was used. In acute disease, systemically administered atovaquone was compared with conventional therapies (pyrimethamine combined with sulfadiazine; clindamycin; and spiramycin). The clinical course of the ocular disease was determined with retinal examination and photography of the fundus. The number of Toxoplasma cysts remaining after treatment was evaluated in aliquots of brain homogenate and in retinal tissue. The effect of atovaquone on cerebral Toxoplasma cyst count was also studied in chronic disease. RESULTS: None of the drugs administered altered the course of the acute disease, judged by clinical examination. Atovaquone alone significantly reduced the number of cerebral Toxoplasma cysts after acute disease. Atovaquone also significantly reduced the cerebral Toxoplasma cyst count in chronic disease. CONCLUSIONS: Tissue cysts are believed to be responsible for reactivation of Toxoplasma retinochoroiditis. Atovaquone has the potential to reduce the risk of recurrent disease.

Acute Disease↗
PubMed1997

Paecilomyces lilacinus endophthalmitis with secondary keratitis: a case report and literature review.

A case of endogenous fungous endophthalmitis with secondary pupillary block glaucoma and corneal invasion requiring penetrating keratoplasty is reported. Initially Paecilomyces lilacinus was isolated from a vitreous and a lens aspirate, but a second vitreous tap revealed Aspergillus fumigatus and P lilacinus. This case highlights the difficulty of diagnosing endogenous fungous endophthalmitis presenting without risk factors and the difficulties of managing such cases using the antifungous agents available. To our knowledge, this is the first case report documenting a progression to stromal keratitis from endogenous endophthalmitis secondary to P lilacinus.

Adult↗
PubMed1997

Conjunctival fibrosis in ocular cicatricial pemphigoid--the role of cytokines.

Ocular cicatricial pemphigoid (OCP) is a systemic, autoimmune disease characterised by conjunctival scarring that is often progressive. The pathophysiology of the fibrosis is unknown. This study aimed to determine which fibrogenic cytokines are present in the conjunctiva in patients with acute and chronic OCP as a first stage in determining the mechanisms of fibrosis. Conjunctival biopsies from patients with acute, subacute and chronic OCP (n=13) were compared to normal conjunctiva (n=10). Production of mRNA for, and expression of, transforming growth-beta1, 2 and 3 (TGF-beta), TGF-beta receptor, platelet derived growth factor (PDGF) and fibroblast growth factor (FGF) were assessed using in situ hybridisation and immunohistochemistry. Acute disease showed increased levels of mRNA for TGF-beta1 and 3, mainly in stromal fibroblasts and macrophages. In the stroma, there were concordant increases in latent and activated TGF-beta1 and 3 and TGF-beta receptor expression by fibroblasts. There were no significant increases in the expression of TGF-beta2, PDGF or FGF in acute disease. No cytokines or receptors were significantly increased in chronic disease. Acutely inflamed conjunctiva in OCP is associated with significant stromal levels of TGF-beta1 and 3 but not PDGF or FGF and none were increased in chronic disease. This suggests that TGF-beta may have a key role in the pathogenesis of the fibrosis. The absence of fibrogenic cytokines in chronic progressive OCP provides support for the proposal that fibroblasts in OCP conjunctiva may remain functionally and morphologically abnormal after the withdrawal of cytokine influences.

Acute Disease↗
PubMed1997

New therapeutic options in uveitis.

Most patients with sight-threatening posterior uveitis eventually end up on systemic medication to control their disease. Although the more aggressive approach to the use of these drugs does offer the patient a better chance of significant visual improvement at least in the short term, this is often associated with severe systemic side-effects in both the young and older patient. Cyclosporin has become a very useful second-line agent as a steroid sparer in those patients who can tolerate it. However, it is not suitable for or effective in everyone and the other currently available drugs are often of limited effectivity or associated with major systemic sequelae. This paper summarises the therapeutic approaches currently being examined to define whether they have a role in the better management of these patients in the future. Particularly exciting is the potential for sustained intraocular drug delivery so that adequate drug levels are achieved inside the eye without the necessity for systemic administration.

Adrenal Cortex Hormones↗
PubMed1997

Adhesion molecule expression in vivo on extraocular muscles (EOM) in thyroid-associated ophthalmopathy (TAO).

TAO is an autoimmune condition characterized by mononuclear cell infiltration of the extraocular muscles (EOM) and/or the orbital fat/connective tissue with associated deposition of glycosaminoglycans (GAG) in the interstitial spaces. In this study, the presence and distribution of the vascular adhesion molecules intercellular adhesion molecule-1 (ICAM-1), endothelial-leucocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1) and the leucocyte integrins CD11a/CD18, CD11b/CD18, CD11c/CD18 were investigated. Nineteen EOM biopsies were collected from 17 patients with early (n = 6) and late (n = 13) TAO as well as from 12 non-TAO control patients. Consecutive cryostat sections of these biopsies were immunostained with MoAbs to the above-mentioned molecules and haematoxylin and eosin. Primary antibody binding was visualized using an avidin-biotin system. In early untreated TAO specimens, the interstitial and perimysial connective tissue surrounding EOM fibres and numerous mononuclear cells stained strongly for ICAM-1. In contrast, the vascular endothelial cells (ulex lectin-positive) stained strongly for ELAM-1 (E-selectin), VCAM-1 as well as ICAM-1. In late disease, the same distribution of immunoreactivity for ICAM-1, ELAM-1 and VCAM-1 was observed, but with significantly lower staining. The leucocyte integrins (CD11a, CD11b, CD11c) were again expressed at significantly higher levels in early TAO specimens compared with late TAO specimens and were minimal or absent in the EOM biopsies harvested from control patients. In conclusion, increased expression of adhesion molecules studied correlated with early active disease and was reduced in later stages.

Adult↗
PubMed1997

Analysis of extraocular muscle-infiltrating T cells in thyroid-associated ophthalmopathy (TAO).

TAO is characterized by an autoimmune process affecting the orbital contents. T cells have been suggested to have a major role in pathogenesis, but so far only limited data are available to clarify the extraocular muscle (EOM)-infiltrating T cell phenotype, antigenic reactivity and cytokine profile in TAO patients. In the present study, biopsies of affected EOM were taken and the infiltrating T cells isolated and expanded in vitro with mitogen. Their phenotype was determined by flow cytometric (FACS) analysis and compared with peripheral blood-derived T cell lines, treated in the same way from the same patient. Cytokines present in the supernatant after mitogen stimulation of the T cell lines were assayed by ELISA. In addition, cytokine mRNA present at the time of biopsy was determined by rapid RNA extraction from EOM and reverse transcription-amplification with specific cytokine oligonucleotide probes (IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL- 15, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha)). In the T cell lines from two patients, proliferation assays were carried out with antigens derived from thyroid gland, EOM and a thyrotropin (TSH) receptor preparation. Most T cell lines were CD4+, CD45RO+, and TCR alpha/beta+, both from the EOM and the peripheral blood. A wide variety of cytokines was detected by analysis of supernatants or mRNA, but the profiles were not identical comparing the two approaches. However, IL-4 was detected by both. Dose-dependent proliferation was observed in response to thyroid extract in a biopsy-derived T cell line. In conclusion, EOM-infiltrating T cells from patients with TAO, expanded in vitro, were chiefly CD4+ and produced a mixture of cytokines, including IL-4. The proliferation data suggest that there are thyroid-reactive T cells in EOM.

Adult↗
PubMed1997

Reassessment of the PAS patterns in uveal melanoma.

BACKGROUND: Previous work has highlighted the prognostic importance of patterns of periodic acid Schiff (PAS) staining (the Folberg patterns) in uveal melanoma. These patterns have been ascribed to blood vessels but the patterns are different from those seen with other staining techniques for blood vessels. It has recently been shown that microvessel density is the dominant prognostic factor in uveal melanoma. This study reinvestigates the nature and significance of the PAS patterns. METHODS: The PAS patterns were compared with the patterns seen with conventional connective tissue stains and with the patterns seen in sections stained for the presence of blood vessels (by immunohistochemistry for factor VIII related antigen). The PAS patterns were determined on a panel of 117 cases of uveal melanoma. The prognostic significance of each of these patterns was determined and, as more than one pattern can exist in a tumour, principal components analysis was performed to determine the number of underlying factors. RESULTS: Comparison of the PAS patterns with other stains demonstrates that they are based on connective tissue including fibrovascular tissue. Five of the nine PAS patterns carried prognostic significance on univariate analysis. Principal components analysis suggested that these patterns represented three underlying factors, which were tentatively identified as representing disordered growth (factor 1), emergence of rapidly growing subclones (factor 2), and section orientation (factor 3). CONCLUSIONS: The PAS patterns are based on fibrovascular tissue and can be ascribed to three underlying factors. The first two of these factors carried prognostic significance and the first (disordered growth) retained independent prognostic significance in a multivariate Cox model which included microvessel density and tumour size.

Biomarkers, Tumor↗
PubMed1997

Assessment of a standard treatment protocol on visual outcome following presumed bacterial endophthalmitis.

AIMS: The aim of this prospective study was, firstly, to judge the effect of early aggressive treatment with a standardised regimen of high dose broad spectrum intraocular and systemic antibiotics on visual outcome and, secondly, to assess the sensitivity of isolated organisms to the treatment regimen utilised. METHODS: Thirty two consecutive patients presenting with presumed bacterial endophthalmitis were treated and completed follow up. In every case, intraocular sampling was undertaken and treatment with intraocular vancomycin, amikacin, and systemic ciprofloxacin was commenced immediately, followed by systemic steroids 1 day later. RESULTS: In 69% of patients vision improved with 47% achieving a final visual acuity of 6/36 or better and 31% achieving 6/12 or better. Of the intraocular samples taken from post-surgical and post-traumatic cases, 10/27 (37%) and 3/5 (60%) were culture positive, respectively. All the bacteria isolated were sensitive to at least one of the three antibiotics used. CONCLUSIONS: The study demonstrated that the combination of vancomycin, amikacin, and ciprofloxacin is adequate as a standard regimen for the treatment of most patients with suspected bacterial endophthalmitis. The prognosis for a good visual outcome, however, remains poor with 15/27 (55%) post-surgical and 2/5 (40%) post-traumatic cases achieving a final acuity of 6/60 or less.

Adult↗
PubMed1996

Microvessel count predicts survival in uveal melanoma.

Microvessel density has become established as an important prognostic indicator for many tumor types. This study investigates the microvessel density as a prognostic factor for survival in patients with uveal melanoma, which is the commonest intraocular tumor and has a clear tendency for metastatic spread to the liver. Factor VIII-related antigen was identified immunohistochemically in bleached sections from 123 tumors. Maximum blood vessel density in an area of 0.25 mm2 was recorded, along with other accepted prognostic information. Microvessel density was the single most important prognostic factor on univariate testing, and in a Cox proportional hazard model, tumor size was the only other variable to be entered. No other accepted prognostic factor entered the model. We conclude that microvessel density is an important prognostic factor for survival in patients with uveal melanoma and allows the identification of high-risk patients for whom adjuvant therapy should be considered.

Biomarkers, Tumor↗
PubMed1996

Managing HIV. Part 5: Treating secondary outcomes. 5.11 HIV and eye disease.

Blindness is a threatening complication of HIV infection, but one that can be prevented by correct diagnosis and management of ocular disease. The general practitioner can play a vital role in diagnosis by being familiar with the types of ocular disease seen at different stages of HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1996

Ophthalmology.

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Ambulatory Surgical Procedures↗
PubMed1996

Lymphocyte migration across the anterior and posterior blood-retinal barrier in vitro.

The migration of lymphocytes through monolayers of rat retinal pigment epithelium (RPE) and retinal vascular endothelium, which form the posterior and anterior blood-retinal barrier (BRB) respectively, was investigated in vitro. After a 4-hr assay the migration of untreated peripheral lymph node (PLN) cells through RPE monolayers was negligible (<1%) with only a small increase found after activation of the PLN cells with concanavalin A or by cross-linking CD3. Activation of the RPE with IFN-gamma augmented migration with maximal PLN cell migration being achieved with a combination of CD3 cross-linking and IFN-gamma activation (17% migration). The highest level of lymphocyte migration was observed with three CD4+ antigen-specific T cell lines specific for purified protein derivative (PPD; 33% migration), ovalbumin (OA; 31%), and S-antigen (S-Ag; 57%). Migration of both untreated and Con A-activated PLN cells through retinal endothelial cells (EC) from PVG rats was negligible, whereas the migration of the antigen-specific T cell lines was 23, 29 and 23% for PPD, OA, and S-Ag lines, respectively. Migration of these cell lines through retinal endothelium derived from Lewis rats was significantly greater (44% for PPD, 39% for OA, and 39% for S-Ag) which corresponded with a greater expression of ICAM-1 on the EC.

Animals↗
PubMed1996

The painful eye.

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Anti-Bacterial Agents↗
PubMed1996

The effect of TNF-alpha and IL-6 on the permeability of the rat blood-retinal barrier in vivo.

The blood-retinal barrier (BRB), which is formed by the retinal vascular endothelium and the retinal pigment epithelium, is responsible for controlling the passage of cells and molecules into the neuroretina. During ocular inflammatory diseases, however, this selective control is altered due to changes in BRB function such as increased permeability and leucocyte recruitment. The causative factors leading to barrier breakdown are not entirely understood although cytokines have recently been implicated. We have investigated the effect of the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) upon the integrity of the rat BRB. Lewis rats received a dose of each cytokine by intravitreal injection and the permeability of the BRB was assessed using the smaller molecular weight vascular tracer 14C mannitol. A significant opening of the barrier to mannitol was detected following an intravitreal injection of 2 x 10(4) U of TNF-alpha which persisted from day 1 to day 5 post-injection (PI). The permeability of the BRB returned to normal values by day 7 PI. Only occasional mononuclear inflammatory cells were seen in the retina and vitreous of the TNF-alpha-treated eyes although they remained in evidence up to day 5 PI. In the TNF-alpha-infected eye there was immunohistological evidence of activation of tissue-resident cells, particularly in the inner plexiform layer. Of particular interest was the observation that the BRB of the non-injected contralateral eye also exhibited increased permeability over a similar time-course but without any evidence of cellular infiltration or activation of tissue-resident cells. Unlike TNF-alpha, the administration of 1 x 10(3) U of IL-6 into the vitreous caused no measurable increase in BRB permeability despite inducing a small infiltration of inflammatory cells.

Animals↗
PubMed1996

Biochemical cure of recurrent acromegaly by resection of cervical spinal canal metastases.

Pituitary carcinoma with metastatic endocrine secreting tissue is rare. Eight cases of malignant, growth hormone-secreting tumours, all metastatic within the central nervous system have been previously described. Complete surgical resection was not possible and the patients died within 4 years of presentation with distant spread. Here we describe the first case of an apparent surgical cure of a somatotroph carcinoma metastatic to the cervical spine, documented by biochemical assessment and magnetic resonance and radioligand imaging. The possibility that intrathecal metastasis of somatotroph tumours may be responsible for some cases of treatment resistant acromegaly is discussed.

Acromegaly↗