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Biomedical subjects

F A Billson

Publications and source records attributed to F A Billson.

At least 19 recordsLinked to original sources

The effect of successful contact lens wear on mucosal immunity of the eye.

OBJECTIVE: This study aimed to assess the effect of contact lens wear on the mucosal defenses of the outer eye against infection. DESIGN: A case-controlled study of daily contact lens wearers in their initial 6 months of contact lens wear. PARTICIPANTS: Contact lens wearers (mean age, 23.1 years; 47 subjects) were compared with age-matched control subjects (mean age, 24.7 years; 44 subjects). INTERVENTION: Outer eye defenses were studied by assay of tear constituents and quantitative conjunctival microbiology. MAIN OUTCOME MEASURES: Antimicrobial activity of tears was studied by assay of total immunoglobulin A (IgA), IgA isotype-specific antibodies reactive with Escherichia coli, Haemophilus influenzae, Staphylococcus epidermidis, albumin and lysozyme, and the ocular surface microbial load determined using quantitative microbiology of the conjunctival sac. RESULTS: The IgA isotype-specific antibodies reactive with E. coli (P = 0.03) and S. epidermidis (P = 0.068) were lower in contact lens wearers, but antibody:albumin ratios were not significantly different in the two groups. Contact lens wear also had no significant effect on tear IgA, albumin, or lysozyme or its ratios with albumin. Bacterial numbers and colonization rates for coagulase-negative staphylococci were greater in contact lens wearers than in age-matched control subjects. Corynebacterium sp. and non-Enterobacteriaceae (P = 0.007) were isolated more frequently and in greater numbers from contact lens wearers. Colonization rates were increased for Corynebacterium sp., but non-Enterobacteriaceae were transient. In both daily contact lens wearers and age-matched control subjects, most conjunctival flora were transient rather than colonizing, and no subject developed an outer eye infection during the study. CONCLUSION: These results suggest that daily contact lens wear does not significantly alter the mucosal defenses of the outer eye that function to eliminate organisms from the conjunctival sac and prevent outer eye infection.

Adult

Vincristine- and cisplatin-induced apoptosis in human retinoblastoma. Potentiation by sodium butyrate.

Chemotherapy alone has largely been unsuccessful in controlling retinoblastoma growth, and has traditionally been limited in use as an alternative to irradiation for the treatment of retinoblastoma. Recently, clinical studies combining chemotherapy with local therapies, including radiotherapy, laser therapy or cryotherapy and in some cases, cyclosporine A, have been effective in treating retinoblastoma. Differentiating agents may also be combined with chemotherapy to enhance the action of cytotoxic drugs on tumor cell growth, although this approach has not been fully investigated in retinoblastoma. In this study, we evaluated the cytotoxic response of human retinoblastoma cell lines (Y79 and WERI-Rb1) to two chemotherapy agents commonly used in treating retinoblastoma, vincristine (VCR) and cisplatin (CDDP). Retinoblastoma cells have been shown to be sensitive to the differentiating agent sodium butyrate, and cell lines were also treated with a combination of VCR or CDDP with sodium butyrate, and the effects on retinoblastoma viability assessed. Both VCR and CDDP induced dose-dependent death of Y79 and WERI-Rb1 cells, accompanied by nuclear and cytoplasmic condensation and DNA laddering, features characteristic of apoptosis. Inhibitors of macromolecular synthesis, cycloheximide and actinomycin-D, significantly reduced VCR- and CDDP-induced apoptosis, although putative endonuclease inhibitors zinc sulphate and aurintricarboxylic acid had no apparent effect. Treatment with 0.5 mM or 1 mM sodium butyrate combined with VCR or CDDP significantly increased induction of apoptosis by these agents. This augmentation of chemotherapy-induced apoptosis may have implications for retinoblastoma therapy.

Antineoplastic Agents

Effect of bile acids on fibroblast proliferation and viability.

PURPOSE: To examine the in vitro effects of bile acids and salts on the viability, growth and morphology of human Tenon's capsule fibroblasts. METHODS: Human Tenon's capsule fibroblasts were grown from explants in culture and used between passages 3 and 5. Fibroblasts (n = 3) were treated in triplicate with deoxycholic acid (DA), sodium deoxycholate (NaD) and cholic acid (CA) at concentrations between 50 microM and 1 mM. Cell viability and growth were assessed with trypan blue staining and haemocytometer counting, and a colorimetric (MTT) assay. Morphology was assessed with light microscopy and cresyl violet staining. RESULTS: A dose-dependent decrease in viability was observed following bile acid treatment (24 and 48 h) where the effects of DA > NaD > CA. The LD50 values at 48 h for DA, NaD and CA were 300 microM, 400 microM and 720 microM respectively. Cell growth following bile acid treatment was reduced compared with controls. Fibroblasts treated with bile acids displayed a loss of normal spindle-shaped morphology and multiple processes, some with varicosities, extended from many cells. These changes were dose-dependent, and at higher concentrations cells became detached and were non-viable (trypan-blue-positive). Extensive cell death was observed in cultures treated with DA 400 microM, NaD 500 microM and CA 800 microM. CONCLUSIONS: Lower doses of bile acids and salts reduced in vitro fibroblast growth associated with morphological changes; higher doses induced fibroblast cytotoxicity. These observations suggest that bile acids and salts, in particular DA, may be useful in regulating wound fibrosis following trabeculectomy surgery.

Adolescent

Exudative macular degeneration and intravitreal triamcinolone: 18 month follow up.

PURPOSE: To evaluate the safety and efficacy of intravitreal triamcinolone after 18 months of follow up in patients with age-related macular degeneration and subfoveal or juxtafoveal choroidal neovascularization considered unsuitable for laser photocoagulation. METHODS: Thirty eyes of 28 patients, referred from general eye clinics as well as the private clinic of one of the authors to a hospital-based retinal out-patient clinic, were treated with an intravitreal injection of triamcinolone (4 mg). The primary outcome measure was the proportion of eyes with loss of six or more lines on a Bailey-Lovie Chart. The incidence of adverse events associated with treatment was also observed. RESULTS: Of the 20 eyes with initial visual acuity (VA) of 6/60 or better, the vision was maintained (+/-1 Bailey-Lovie lines) in 11 eyes (55%), while six eyes (30%) suffered severe visual loss (six or more lines). The VA improved by five to six lines in three of 10 eyes with initial vision of 3/60 or worse. Three of four eyes receiving a second injection suffered either progressive cataract or elevated intra-ocular pressure (IOP) requiring cataract surgery and/or filtering surgery. One of 26 eyes (3%) receiving a single injection showed progression of cataract and elevation of IOP within 6 weeks of treatment and required anti-glaucoma medication for 6 weeks. Progression of nuclear sclerosis 8-12 months after treatment was observed in six of 26 eyes (23%) receiving a single injection. CONCLUSIONS: The results of the present study suggest that a single intravitreal injection of 4 mg triamcinolone is reasonably well tolerated by the human eye. The rate of development of severe visual loss was less than reported for historical controls. Because the results are preliminary and uncontrolled, the treatment should not be used routinely until its benefit to patients is established by a prospective, randomized controlled study.

Aged

Electrode position and the multi-focal visual-evoked potential: role in objective visual field assessment.

PURPOSE/METHODS: To improve the performance of visual-evoked potentials (VEP) in the assessment of the human visual field, the multi-focal cortically scaled pattern VEP was recorded up to 250 of eccentricity in normal subjects. Monopolar and varying bipolar electrode positions were used. RESULTS: The monopolar response was strongly biased towards the lower hemifield. Bipolar leads straddling the inion (2 cm above and below) achieved approximately equal signals from the upper and lower visual field. Division into sectors of similar wave-form augments the analysis compared with summed full-field responses. CONCLUSION: With this technique, the multi-focal VEP can be used to objectively assess the visual field.

Cerebral Cortex

Multifocal topographic visual evoked potential: improving objective detection of local visual field defects.

PURPOSE: To investigate the relationships between the pattern stimulation of different parts of the visual field (up to 25 degrees of eccentricity), the electrode position, and the cortical response to improve objective detection of local visual field defects. METHODS: The human visual evoked potential (VEP) was assessed using multifocal pseudorandomly alternated pattern stimuli that were cortically scaled in size. Monopolar and bipolar electrode positions were used. The visual field was investigated up to 26 degrees of eccentricity. Twelve normal subjects and seven subjects with visual field defects of different nature were studied. RESULTS: Although the monopolar response is heavily biased toward the lower hemifield, bipolar leads overlying the active occipital cortex (straddling the inion) demonstrate good signals from all areas of the visual field tested. The amplitude is almost equal for the averaged upper and lower hemifields, but the polarity is opposite, causing partial cancellation of the full-field VEP. The degree of cancellation depends mainly on latency differences between the vertical hemifields. The bipolar VEP corresponded well with Humphrey visual field defects, and it showed a loss of signal in the scotoma area. CONCLUSIONS: The multifocal VEP demonstrates good correspondence with the topography of the visual field. Recording with occipital bipolar electrode placement is superior to standard monopolar recording. To avoid a full-field cancellation effect, a separate evaluation of upper and lower hemifields should be used for the best assessment of retinocortical pathways. This technique represents a significant step toward the possible application of the multifocal VEP to objective detection of local defects in the visual field.

Adult

Human retinoblastoma: in vitro differentiation and immunoglobulin superfamily antigen modulation by retinoic acid.

Suspension and attachment cultures of Y79 human retinoblastoma cells were treated with all-trans retinoic acid (RA) for up to 10 days to assess its effect on growth and cell-surface expression of immunoglobulin superfamily antigens MHC class I and class II, ICAM-1, NCAM and Thy1. RA up to 10 microM induced growth inhibition, and marked morphological differentiation with extension of prominent processes resembling neurites was seen in attachment cultures. However, above 10 microM RA produced extensive cell death. We also observed increased cell-surface expression of MHC class I, ICAM-1, NCAM and Thy1 on Y79 cells treated with 10 microM over 10 days; constitutive MHC class II expression was not apparent, nor did RA treatment appear to induce Y79 cells to express MHC class immunoreactivity. The up-modulation of cell-adhesion molecules (NCAM, ICAM-1 and Thy1) and immune recognition molecules (NCAM, ICAM-1 and MHC class I), associated with reduced growth and tumour cell differentiation, suggests that RA may have a potential role in regulating the growth and development of retinoblastoma tumours.

Adjuvants, Immunologic

Choroidal melanoma: a review of the experience of the Sydney Eye Hospital Professorial Unit 1979-1995.

PURPOSE: This study examines 90 patients presenting with choroidal or ciliochoroidal melanoma to the Professorial Unit at the Sydney Eye Hospital. The indications for treatment, and the outcome for the eye and vision are presented together with an account of mortality and the incidence of metastases. METHODS: A retrospective analysis of 90 choroidal melanoma patients managed by one surgeon over a 16-year period was undertaken. Initial findings, investigations performed, incidence of metastatic disease, treatment received and complication rates and mortality, where applicable, were recorded. RESULTS: The group was followed for an average of 64 months (range, 5-172 months). Primary treatment was with either iodine125 (125I) brachytherapy, local excision or enucleation. Radiation retinopathy was prominent in 125I cases resulting in poor visual acuity when the tumour resided in the posterior pole. Local excision even of large tumours was effective particularly if peripheral. Overall metastatic disease was seen in 11% with 5-year survival rates for the metastatic group being 10%. Prognosis after diagnosis of metastases was poor. CONCLUSIONS: Specific therapy for choroidal melanoma must relate to the size and location of the tumour at the time of diagnosis. Visual outcome relates directly to the proximity of the tumour to the optic nerve and fovea. Metastatic disease latency can be prolonged; therefore caution about prognosis is required long after therapy is given. The 5-year survival is encouraging with all forms of therapy. However, as the natural history of ocular melanoma is variable and not fully delineated it is important to monitor the effects of conservative therapy. Further long-term survival data is required to distinguish whether one form of treatment is advantageous over the others, although case-control studies are difficult for ethical and practical reasons. In this regard the Collaborative Ocular Melanoma Study (COMS) will provide further evidence for the safety and efficacy of conservative therapy with brachytherapy compared to enucleation.

Adult

Effect of human vitreous and hyalocyte-derived factors on vascular endothelial cell growth.

PURPOSE: In the present study we have examined the effects of human vitreous and hyalocyte-conditioned medium on human umbilical vein endothelial cells (HUVEC). METHODS: Human umbilical vein endothelial cells were cultured and treated in quadruplicate with human vitreous and hyalocyte-conditioned medium at different concentrations. Cell numbers were counted on days 1, 3, 5 and 7. Morphological changes and the viability of cells after treatment were also monitored. RESULTS: The results indicate that both human vitreous and hyalocyte-conditioned medium inhibit proliferation and reduce the viability of HUVEC in vitro. These inhibitory effects were dose- and time-dependent. CONCLUSIONS: The observations suggest that human hyalocytes and vitreous contain anti-angiogenic factors that influence vascular endothelial cell-growth. These results, combined with those of previous studies, may yield important information about the functional role of vitreous and hyalocytes in intraocular vascular regression.

Adult

Development of microglial topography in human retina.

The development of microglial topography in wholemounts of human retina has been examined in the age range 10-25 weeks gestation (WG) using histochemistry and immunohistochemistry for CD45 and major histocompatibility complex class II antigens. Microglia were present in three planes corresponding to the developing nerve fibre layer/ganglion cell layer, the inner plexiform layer and the outer plexiform layer. Distribution patterns of cells through the retinal thickness and across the retinal surface area varied with gestational age. Microglia were elongated in superficial retina, large and ramified in the middle plane, and small, rounded and less ramified in deep retina. Intensely labeled, rounded profiles seen at the pars caeca of the ciliary processes, the retinal margin and at the optic disc may represent precursors of some retinal microglia. At 10 WG, the highest densities of microglia were present in middle and deep retina in the far periphery and at the retinal margin, with few superficial microglia evident centrally at the optic disc. At 14 WG, high densities of microglia were apparent superficially at the optic disc; microglia of middle and deep retina were distributed at more central locations although continuing to concentrate in the retinal periphery. Microglia appear to migrate into the developing human retina from two mains sources, the retinal margin and the optic disc, most likely originating from the blood vessels of the ciliary body and iris, and the retinal vasculature, respectively. The data suggest that the development of microglial topography occurs in two phases, an early phase occurring prior to vascularization, and a late phase associated with the development of the retinal vasculature.

Age Factors

Induction of apoptosis by sodium butyrate in the human Y-79 retinoblastoma cell line.

The mode of cell death induced in the Y-79 human retinoblastoma cell line by sodium butyrate (SB), a short-chain fatty acid with potent inhibitory effects on the growth of many transformed cell lines, was investigated by fluorescence and transmission electron microscopy, agarose gel electrophoresis, and metabolic studies. While SB (< 1 mM) resulted in marked morphological differentiation, higher concentrations (1-4 mM) induced predominantly apoptotic involution in Y-79 in a concentration-dependent fashion after a latent period of 24 h. Dying cells displayed the characteristic morphology of apoptosis accompanied by DNA laddering with agarose gel electrophoresis. Extensive cell necrosis was apparent with 0.5 M SB. Induction of apoptosis and DNA laddering by SB was reduced by putative inhibitors of RNA and protein synthesis, but not putative endonuclease inhibitors. These results are important for understanding the mode of action of sodium butyrate as a potential cancer chemotherapeutic agent.

Apoptosis

Hydrolases of anterior segment tissues in the normal human, pig and rat eye: a comparative study.

The distributions of the hydrolases acid and alkaline phosphatase (AP and ALP), N-acetyl-beta-D-glucosaminidase (NAG), beta-glucuronidase (beta-Gluc), beta-galactosidase (beta-Gal), non-specific esterase (UE), dipeptidylpeptidases II and IV (DPPII and DPPIV), aminopeptidases M and A (APM and APA), and gamma-glutamyltransferase (GGT) were investigated in the human, pig and Lewis rat normal anterior segment by histochemical methods. The distribution of the above hydrolases, particularly that of proteases, varied between ocular tissues and between the three species. Lysosomal hydrolases together with GGT and ALP were consistently active in the corneal epithelium, stroma and endothelium in all three species; the corneal distribution and activity of beta-Gal, APM, APA and DPPIV, however, displayed interspecies variation. The angular tissues showed similarities for most hydrolases with the exceptions of beta-Gal, UE, APM, APA and DPPIV. In all eyes examined strong ciliary epithelial activity for AP, beta-Gal, UE, GGT and ALP was observed in the pars plicata; only the pig eye also displayed strong DPPIV activity in this area. Regional differences in hydrolase distribution in the iris were observed in all species. A post-mortem freezing delay of longer than 24 h resulted in a decrease in hydrolase activity.

Aged

Modulation of MHC class II expression in the absence of lymphocytic infiltrates in Alzheimer's retinae.

This study describes the expression of MHC class II antigens in retinal flat mounts from normal donors and patients with Alzheimer's disease (AD). We confirm previous observations of MHC class II immunoreactivity on microglia in normal retinae, while observing insignificant levels of reactivity on endothelial cells (EC). A significantly increased level of MHC class II expression was detected in AD retinae. This increased immunoreactivity was found to occur in the absence of lymphocytic infiltrates, suggesting that the pathogenesis of AD in the retina may be distinct from that reported to occur in some regions of the brain. MHC class II expression, measured using computerized optical densitometry, appeared to be increased principally as a result of induced MHC class II immunoreactivity on EC. Ramified microglia and perivascular macrophages, although hypertrophied, appeared to show unchanged levels of MHC class II expression. These findings are consistent with earlier suggestions that both aberrant MHC class II expression and suppressor activity of resident macrophages may restrict immune responses.

Adult

Suppurative corneal ulceration in Bangladesh. A study of 142 cases examining the microbiological diagnosis, clinical and epidemiological features of bacterial and fungal keratitis.

Suppurative keratitis is an important preventable cause of blindness, particularly in the developing world. This study analyses 142 cases of suppurative keratitis referred to Chittagong Eye Infirmary Bangladesh. Some 53.5% of cases were bacterial and 35.9% were fungal. The five most common pathogens were: Pseudomonas sp. 24%, Streptococcus pneumoniae 17%, Aspergillus sp. 13%, Fusarium sp. 7% and Curvularia sp. 6%. Gram stain and culture results were consistent in 62.6% of cases. Previous antibiotic treatment was a significant factor for failure of culture isolation and less so for Gram stain failure. On Gram stain, 55.9% of pseudomonal cases were missed, but only 2% of fungal cases were missed. Over all, Gram stain had a sensitivity of 62% and positive predictive value of 84% for bacterial cases, and 98% and 94% for fungal cases, respectively. Fungal ulcers were typically filamentous, but an antecedent history of trauma was not common. The most frequent injury was due to rice grains, but the inoculum appeared to be introduced during eye washing with contaminated water. Pseudomonal ulcers occurred most frequently in the monsoon season, and Fusarium cases were seen only in the hot, dry season.

Adolescent

Intermediate filament expression in human retinal macroglia. Histopathologic changes associated with age-related macular degeneration.

PURPOSE: Intermediate filament expression by retinal macroglia was studied in normal eyes, normal eyes of older subjects, and eyes of subjects with age-related macular degeneration (AMD), classified on the basis of histopathologic assessment of the retinal pigment epithelium (RPE), choroid, and donor age. METHODS: Adult human retinae (N = 43) were divided into three groups: normal (< 50 years of age, with normal RPE and choroid); normal eyes of older subjects (> 50 years with normal RPE and choroid); and eyes of subjects with AMD (> 50 years with histopathologic findings indicative of AMD), on the basis of histopathologic assessment of the RPE/choroid and donor age. Intermediate filament expression by retinal macroglia was studied in cryostat sections and in retinal flatmounts using avidin-biotin-peroxidase immunolabeling of antibodies to glial fibrillary acidic protein (GFAP) and vimentin. RESULTS. Analyses of immunohistochemically labeled retinal sections revealed similar distributions of vimentin reactivity in retinae of each group. Distributions of GFAP in normal and normal aged retinae were similar, but sections of AMD-affected retinae showed evidence of GFAP expression by Müller cells. In flatmounts, vimentin distribution was similar in the three groups, but GFAP labeling revealed hypertrophic astrocytes, which were absent from normal retinae, in 17% of aged retinae and 55% of AMD-affected retinae. Deeply penetrating, GFAP-positive processes were observed in 17%, 27%, and 55% of normal, normal aged, and AMD-affected retinae, respectively. CONCLUSIONS: Variation in GFAP and vimentin expression in retinal macroglia is affected by increasing age, and a distinctive variation of intermediate filament expression in retinal macroglia is associated with the pathogenesis of AMD.

Adolescent