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Biomedical subjects

R A Lewis

Publications and source records attributed to R A Lewis.

At least 199 records · Page 11Linked to original sources
PubMed1989

The effects of apraclonidine on conjunctival oxygen tension.

A prospective, randomized study evaluated the effects of unilateral, topical 1% apraclonidine hydrochloride on conjunctival oxygen tension in 10 normal volunteers using a conjunctival oxygen monitor. Conjunctival oxygen tension and intraocular pressure were measured prior to instillation of apraclonidine, then at 1, 3, and 5 hours. Apraclonidine was found to significantly decrease conjunctival oxygen tension 76% at 1 hour compared with baseline values. At 3 hours conjunctival oxygen tension was decreased to 56% and at 5 hours to 10% of baseline. Intraocular pressure was lowered maximally at 3 hours to 40% of baseline measurements in the treated eye. The contralateral eye had a small decrease in conjunctival oxygen tension and intraocular pressure that was not statistically significant. Lid retraction and conjunctival blanching were noted to occur maximally between 1 and 3 hours. Further study is needed to determine if the apraclonidine-induced conjunctival hypoxia noted in this study has clinical significance for ocular blood flow, particularly in patients with glaucoma.

Administration, Topical↗
PubMed1989

Determination of clefts in receptor structures.

The automatic determination of atoms which comprise a cleft in a receptor is of great importance in computer-aided drug design. X-ray studies of ligand/receptor pairs show that the ligand is often located in a cleft so that this structural feature will indicate a putative binding site. This information can be used in the design of new drugs by database searching and by automatic structure generation. The methods presented in this paper will find the complete accessible surface in a slice through a receptor and also all the clefts and dimples in this surface, using the properties of the Voronoi tessellation of the receptor. Clefts and binding sites can now be determined quickly and without observer bias.

Algorithms↗
PubMed1989

A comparison of the ocular hypotensive efficacy of once-daily and twice-daily levobunolol treatment.

The authors compared the ocular hypotensive efficacy of two different treatment regimens of levobunolol 0.5% in a double-masked, randomized, controlled clinical trial. Seventy-one patients with open-angle glaucoma or ocular hypertension received levobunolol 0.5% as their sole glaucoma medication either on a once-daily or twice-daily treatment regimen for 3 months. Approximately 81% of the patients in the once-daily treatment group and 88% of subjects in the twice-daily treatment group successfully completed the 3-month study period. The overall mean decrease in intraocular pressure (IOP) was 4.5 mmHg in the once-daily group and 5.6 mmHg in the twice-daily group. These differences were not statistically different. For both treatment groups, effects on mean heart rate and blood pressure were minimal. The authors' data from this population suggest that once-daily treatment with levobunolol is an effective glaucoma regimen.

Blood Pressure↗
PubMed1989

Visual field loss in migraine.

Ocular symptoms are a common, though transient, initial component of migraine. Although permanent visual loss has been reported in a limited number of patients, detailed evaluations of the visual field using current techniques have not been conducted. This study examined the prevalence of visual field loss in patients with migraine, using an automated static perimeter. All patients had at least a 2-year history of migraine (as diagnosed by a neurologist) and no ocular problems (by history or as determined by a visual screening examination consisting of acuity, intraocular pressure [IOP], and evaluation of the disc). The authors' results for 60 migraine patients showed that 21 (35%) had some form of visual field abnormality (P less than 0.05). The prevalence of visual field loss was greater with increasing age and duration of disease. These results suggest that visual field loss from migraine may be more common than previously considered. This information also may be useful in elucidating the relationship between migraine and certain vascular conditions of the eye.

Adolescent↗
PubMed1989

Recombinant interferon-gamma primes alveolar macrophages cultured in vitro for the release of leukotriene B4 in response to IgG stimulation.

The capacity of interferon-gamma to regulate the generation and release of leukotriene B4 (LTB4) from human alveolar macrophages of normal nonsmoking individuals was evaluated. When alveolar macrophages were incubated for 60 min with heat aggregated IgG (HAIgG), they generated and released 5.7 +/- 1.7 ng of LT B4 per 10(6) cells compared to 1.9 +/- 0.4 ng from cells incubated with buffer alone, P = 0.02. When alveolar macrophages were preincubated with interferon-gamma for 24 h before activation for 60 min with heat-aggregated IgG, the soluble IgG aggregates became a significantly more effective stimulus for LTB4 release, 17.0 +/- 3.9 ng/10(6) cells, P = 0.001, compared to cells incubated in the absence of interferon-gamma and challenged with HAIgG. Interferon-gamma did not alter the response to A23187. This effect of interferon-gamma was both time and dose dependent; it also was specific since neither interferon-alpha nor interferon-beta had a regulatory effect on the release of LTB4 from cells in response to challenge with HAIgG. Preincubation of the alveolar macrophages with interferon-gamma augmented the density of IgG1 receptors by 81.5 +/- 17.3%; neither interferon-alpha nor interferon-beta effected this parameter. Furthermore, monomeric IgG1 blocked HAIgG induced LTB4 release from alveolar macrophages primed with interferon-gamma. Therefore, at least one of the mechanisms by which interferon-gamma primes alveolar macrophages for the production and release of LTB4 in response to stimulation by aggregates of IgG is that of increasing the number of receptors for this stimulus.

Antigens, Differentiation↗
PubMed1989

Choroideremia and deafness with stapes fixation: a contiguous gene deletion syndrome in Xq21.

The study of contiguous gene deletion syndromes by using reverse genetic techniques provides a powerful tool for precisely defining the map location of the genes involved. We have made use of individuals with overlapping deletions producing choroideremia as part of a complex phenotype, to define the boundaries on the X chromosome for this gene, as well as for X-linked mixed deafness with perilymphatic gusher (DFN3). Two patients with deletions and choroideremia are affected by an X-linked mixed conductive/sensorineural deafness; one patient, XL-62, was confirmed at surgery to have DFN3, while the other patient, XL-45, is suspected clinically to have the same disorder. A third choroideremia deletion patient, MBU, has normal hearing. Patient XL-62 has a cytogenetically detectable deletion that was measured to be 7.7% of the X chromosome by dual laser flow cytometry; the other patient, XL-45, has a cytogenetically undetectable deletion that measures only 3.3% of the X chromosome. We have produced a physical map of the X-chromosome region containing choroideremia and DFN3 by using routine Southern blotting, chromosome walking and jumping techniques, and long-range restriction mapping to generate and link anonymous DNA sequences in this region. DXS232 and DXS233 are located within 450 kb of each other on the same SfiI and MluI fragments and share partial SalI fragments of 750 and greater than 1,000 kb but are separated by at least one SalI site. In addition, DXS232, which lies outside the MBU deletion, detects the proximal breakpoint of this deletion. We have isolated two new anonymous DNA sequences by chromosome jumping from DXS233; one of these detects a new SfiI fragment distal to DXS233 in the direction of the choroideremia gene, while the other jump clone is proximal to DXS233 and detects a new polymorphism. These data refine the map around the loci for choroideremia and for mixed deafness with stapes fixation and will provide points from which to isolate candidate gene sequences for these disorders.

Adolescent↗
PubMed1989

Evidence for a neural basis of age-related visual field loss in normal observers.

Many studies have reported a decrease in visual field sensitivity as a function of increasing age in normal individuals. This age-related sensitivity loss has mainly been attributed to reductions in pupil size and transmission losses of the ocular media (particularly the lens), although neural losses in the retina, optic nerve and visual cortex have also been suggested. We evaluated the role of preretinal factors on normal visual field changes associated with aging. The central visual field of both eyes of 62 normal subjects (ages 20 to 72) were evaluated with Program 30-2 of a modified Humphrey Field Analyzer. Three test procedures were employed: (1) a standard visual field evaluation; (2) a yellow target on a yellow background condition (530 nm cutoff filter) to minimize the influence of lens transmission losses with age; and (3) a large target/high background luminance "yellow on yellow" test condition (530 nm cutoff filter, 635 asb background, Size V target) to minimize both pupil size and lens effects on central visual field sensitivity. In addition, relative lens absorption estimates were obtained for each subject. All three test conditions revealed a loss in visual field sensitivity with increasing age (approximately 0.8 dB per decade) but no meaningful differences were found among the three test procedures. Relative lens density increased with age but was not related to visual field sensitivity for any of the three test conditions. These data suggest that normal age-related visual field sensitivity changes are primarily due to neural losses rather than preretinal factors.

Adult↗
PubMed1988

Leukotriene C4 produced by a human T-T hybridoma suppresses Ig production by human lymphocytes.

Multiple signals are involved in the regulation of Ig production by human B lymphocytes. Leukotrienes, especially LTB4, have been shown to inhibit Ig production by increasing the number and function of suppressor lymphocytes. Production of leukotrienes has been demonstrated by mast cells, basophils, eosinophils, polymorphonuclear leukocytes, monocytes, and macrophages. In this paper we demonstrate that a human T-T hybridoma grown at 5 x 10(5) cells/ml constitutively produces 5 ng/ml of LTC4. Furthermore, we demonstrate that either the supernatant from this hybridoma containing 0.5 to 10 ng/ml LTC4 or purified LTC4 in the range of 0.5 to 5 ng/ml can suppress 50 to 70% of Ig production by unfractionated human mononuclear cells, by normal human cells stimulated with Staphylococcus aureus Cowan I and B cell differentiation factors, and by the EBV-transformed B cell line SKW.6 in the presence of B cell differentiation factors. Thus, LTC4 can have direct effects on B cells and may have a role in normal B cell regulation.

Antibody-Producing Cells↗
PubMed1988

Uses of thrombin in ocular surgery. Effect on the corneal endothelium.

Thrombin is a hemostatic factor that induces platelet aggregation and catalyzes the conversion of fibrinogen to fibrin. The potential for its increasing application to a variety of anterior and posterior segment surgery led us to investigate the in vitro effect of thrombin on the corneal endothelium in a sheep model. We examined freshly excised sheep corneas stained with alizarin red and trypan blue after exposure to two different concentrations of thrombin for four hours. The structure of the corneal endothelium appeared to be intact even after prolonged exposure to thrombin at concentrations of 100 and 1000 U/mL. Thrombin appears to be nontoxic to the corneal endothelium in this experimental model.

Adult↗
PubMed1988

The effect of fluorouracil on the corneal endothelium.

The utility of the antiproliferative agent fluorouracil has been demonstrated recently in glaucoma-filtering surgery and in the management of proliferative vitreoretinopathy after vitrectomy. Because of the potential for contact with the corneal endothelium, its toxicity to the endothelium is an important consideration. The effect of fluorouracil on corneal endothelial integrity in an in vitro animal model was studied. Freshly excised sheep corneal buttons were exposed to increasing concentrations of fluorouracil for four hours and were subsequently evaluated microscopically using vital staining with alizarin red and trypan blue. Exposure to normal saline and chlorhexidine gluconate was used to establish negative- and positive-staining controls. Corneal buttons exposed to normal saline or to 1.0 mg/mL or less of fluorouracil had intact endothelial monolayers that completely excluded trypan blue. Corneal buttons exposed to chlorhexidine gluconate or to 10 mg/mL of fluorouracil, however, had severely or totally disrupted endothelial monolayers in which the remaining cells, if any, all had blue-staining nuclei. These results suggest that the threshold concentration for fluorouracil toxicity to corneal endothelium lies between 1 and 10 mg/mL when exposure time is four hours.

Animals↗
PubMed1988

The Williams syndrome. Spectrum and significance of ocular features.

Forty-two subjects with classic features of Williams syndrome were evaluated to ascertain the prevalence and severity of the ophthalmologic features associated with the disorder. Twenty-six (62%) had a stellate pattern of the anterior iris stroma which was observed only in individuals with blue or hazel iris color. Twelve (29%) had strabismus, most commonly esotropia. Hypermetropic discs were noted in 18 of 33 patients (55%), a simplex vertical branching of the central retinal vessels at the disc in 23 (70%), and situs inversus vasorum in 5 (15%). No subject had accentuated vascular tortuosity, which has been reported previously as a hallmark of this syndrome. No ocular manifestation of infantile hypercalcemia was noted in any subject.

Abnormalities, Multiple↗
PubMed1988

The effect of Goldmann applanation tonometry on automated static threshold perimetry.

Automated static threshold perimetry was performed in both eyes of 10 normal and 12 ocular hypertensive subjects treated with a topical beta-blocker, before and after Goldmann applanation tonometry of their right eyes. Both objective statistical comparison and subjective evaluation of the resultant visual fields showed no detrimental effect on visual field test results after applanation tonometry.

Adrenergic beta-Antagonists↗