Asthma mortality in New Zealand: a review with some policy implications.
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Acute Disease↗
Biomedical subjects
M Sears
Publications and source records attributed to M Sears.
Patterns of early visual field loss in open-angle glaucoma.
We examined two groups of patients with primary open-angle glaucoma with distinctly different patterns of early visual field loss using two visual field indices: mean defect and loss variance. Patients were selected on the basis of visual field criteria only. Eight patients were selected for diffuse depression of the differential light sensitivity without localized scotomas (mean defect greater than 3.0 decibels, loss variance less than 10.0 decibels). Seven patients were selected for localized scotomas without diffuse depression of the differential light sensitivity (mean defect less than or equal to 3.0 decibels, loss variance greater than or equal to 20.0 decibels). Patients with diffuse depression manifested intraocular pressures that were higher (mean peak pressure +/- S.E.M., 27.6 +/- 1.2 mm Hg) than those with localized defects (22.4 +/- 1.4 mm Hg). The optic disk rim area of the localized loss group (mean +/- S.E.M., 1.02 +/- 0.15 mm2) was significantly smaller (P less than .05) than the disk rim area of the diffuse loss group (1.33 +/- 0.07 mm2). This difference was largely because of thinner temporal disk rims in the localized loss group. Different patterns of visual field loss may be caused by different mechanisms of glaucomatous optic nerve damage.
Aged↗
Quantitative evaluation of the optic nerve head in patients with unilateral visual field loss from primary open-angle glaucoma.
Measurable structural alterations of the optic nerve head may precede visual field abnormalities in early open-angle glaucoma. The authors studied the optic nerve heads of 10 patients with unilateral visual field loss from primary open-angle glaucoma, and 12 age- and sex-matched normal subjects. Topographic optic nerve head parameters were measured with a system of computerized image analysis (Rodenstock Analyzer, G. Rodenstock Instrumente GMBH, Munich, W. Germany). In patients with asymmetric primary open-angle glaucoma, eyes with normal visual fields had a slightly larger mean (+/- standard error of the mean) disc rim area (0.90 +/- 0.04 mm2) than eyes with glaucomatous visual field defects (0.78 +/- 0.05 mm2). However, both sets of eyes in the asymmetric primary open-angle glaucoma patients had smaller mean disc rim areas (P less than 0.0007) than did the control group (1.27 +/- 0.09 mm2). These findings support the hypothesis that loss of the optic disc rim can be detected before perimetric abnormalities develop in primary open-angle glaucoma.
Female↗
The effect of hCG on cyclic AMP in rabbit ciliary processes.
Experiments designed to address the role of cyclic AMP as a mediator of the eye pressure and aqueous flow reducing effects of human chorionic gonadotropin (hCG) in the rabbit have been conducted. No significant stimulatory effect of hCG on particulate preparations of adenylate cyclase from rabbit ciliary processes could be found under several different experimental conditions. Forskolin, an activator of adenylate cyclase can, in some biological systems, reveal a significant hormonal cyclic AMP response which is undetectable in the presence of hormone alone. Forskolin did potentiate the effect of isoproterenol on cyclic AMP production by intact rabbit ciliary processes. Cyclic AMP production by intact ciliary processes was not affected by hCG, either in the presence or absence of forskolin. Significant specific binding of iodinated hCG to particulate preparations of rabbit ciliary processes could not be detected. These results dispute the role of cyclic AMP as a mediator of the flow and pressure reducing effects of hCG; however, theoretical and methodological complications relating to this interpretation are discussed.
Adenylyl Cyclases↗
Celiprolol versus timolol and placebo: a two week double-blind comparison.
Celiprolol (5%) was compared to timolol (0.5%) and placebo in patients with primary open angle glaucoma or ocular hypertension. A total of 28 patients participated in this double blind study and received treatment for two weeks. Intraocular pressure decreased an average of 4.4 mmHg with celiprolol and 7.1 mmHg with timolol two hours after instillation. This was maintained 12 hours after administration of timolol but not after celiprolol. There was a small but statistically significant decrease in pulse rate 2 hours after administration of timolol (from 72 to 64 beats per minute) which was not observed after celiprolol. Side effects were mild and similar for all 3 groups.
Adrenergic beta-Antagonists↗
Chorionic gonadotropin decreases intraocular pressure and aqueous humor flow in rabbit eyes.
The effect of human chorionic gonadotropin (hCG) on the rabbit eye was studied. Intravitreal injections of hCG in albino rabbits provoked a reduction of intraocular pressure (IOP). Intravenous administration of hCG in single doses of 5,000-10,000 units in male pigmented rabbits caused a significant reduction in IOP from 1.5-5 hr after injection. When two successive intravenous doses of 5,000 units of hCG were given at 0 and 3 hr to pigmented rabbits, a significant reduction of net aqueous flow occurred, as measured by scanning fluorophotometry. These results indicate that the decrease in aqueous flow rate in the rabbit eye after administration of hCG can account for the reduction in IOP.
Animals↗
Comparison of visual field defects in normal-tension glaucoma and high-tension glaucoma.
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Glaucoma↗
Regulation of intraocular pressure during cyclocryotherapy for advanced glaucoma.
Five eyes of five patients with advanced glaucoma were treated with cyclocryotherapy. Intraocular pressure was monitored by applanation tonometry during the procedure and for the first 24 hours postoperatively. Two patients underwent a standard form of treatment, and exhibited two components of acute increases in intraocular pressure as a result of the procedure. Intraoperatively, intraocular pressure increased abruptly to 60 to 80 mm Hg during the freezing phase of cyclocryotherapy and decreased to baseline levels during the thaw phase. Postoperatively, intraocular pressure increased to approximately 50 mm Hg, peaking six hours after the procedure. We devised a method of manometric regulation of intraocular pressure to prevent significant increases during cyclocryotherapy and used it in three patients. This group maintained intraocular pressures of approximately 25 mm Hg intraoperatively, and exhibited blunted postoperative increases. Manometric regulation of intraocular pressure during cyclocryotherapy for advanced glaucoma may protect seriously compromised optic nerves from further damage, and may represent a safer method of treatment.
Adolescent↗
Reproducibility of optic disc measurements with computerized analysis of stereoscopic video images.
Computerized digital image analysis of the optic nerve head was performed using a simultaneous stereoscopic video camera system to provide rapid, quantitative measurements of optic nerve head topography. Determination of the variability of the measurements is required to estimate the magnitude of optic nerve change over time that can be reliably detected. Total variability, operator variability, and interoperator variability were studied. Total variability was assessed by analyzing ten sets of video recordings made in each of seven eyes of seven normal subjects, and in seven eyes of seven patients with glaucoma. The median coefficients of variation for measurements of total variability in glaucoma patients were as follows: vertical disc measurement, 1.4%; horizontal disc measurement, 2.1%; disc area, 1.9%; vertical cup/disc, 3.9%; horizontal cup/disc, 3.3%; disc rim area, 7.5%; and volume, 7.6%. Operator and interoperator variabilities were considerably smaller in magnitude.
Data Display↗
Patterns of early visual field loss in open-angle glaucoma.
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Aged↗
Ocular blood flow in phakic and aphakic monkey eyes.
Alterations in regional ocular blood flow produced by topical epinephrine were studied in phakic and aphakic eyes of Macaca arctoides using the radioactive microsphere technique. Three isotopes were used to make sequential blood flow measurements just prior to topical epinephrine administration, 1 hr later and 3 hr later. Significant reductions of flow were found in the iris, ciliary body, and optic nerve head of both phakic and aphakic groups. Choroidal and posterior optic nerve flow decreased significantly in aphakic eyes only. Decreases in flow were flow decreased significantly in aphakic eyes only. Decreases in flow were maximal at 3 hr. Significant changes in retinal flow were not detected. The implications of these findings regarding epinephrine-induced aphakic cystoid macular edema and the suitability of epinephrine or its derivatives in the treatment of glaucoma are discussed.
Animals↗
Combined effect of forskolin and acetazolamide on intraocular pressure and aqueous flow in rabbit eyes.
Forskolin, a diterpene, a potent and direct stimulator of the catalytic unit of adenylate cyclase, can reduce intraocular pressure when administered topically to rabbit eyes in a 1% suspension. Using an intravitreal plant of fluorescein-dextran, aqueous flow was measured by a modification of the method of Maurice. Forskolin reduces net aqueous flow by 51% compared to the controls. Acetazolamide (25 mg kg-1) administered intravenously reduces net aqueous flow by 45%. Forskolin and acetazolamide together reduce net aqueous flow by 72%, an important additive effect undoubtedly produced by different pathways.
Acetazolamide↗
Human ciliary epithelia in monolayer culture.
The ciliary epithelia of human (one to 12 months old) ciliary processes were isolated by trypsin and EDTA, cultured in Dulbecco's Modified Eagle Medium (DMEM) with 5% fetal calf serum and examined by phase and electron microscopy. The primary cultures were maintained for three to four months. Only a few non-pigmented epithelia adhered and none of them proliferated. After the first passage the culture seemed to consist of only the pigmented epithelia. Most cells were densely pigmented at first, then became less pigmented during successive proliferations. Half of the cells remained densely pigmented after the first subculture, another half remained less pigmented. The cells started to lose their pigment granules at four to six weeks in culture. After three months of culture, the cell sheets became entirely unpigmented. In thin section, most of the pigment granules in the cells at two weeks in culture were pre-melanosomes, and half of them were at the earliest stage of pre-melanosomes. Monolayer cells possessed basement membranes. At 14 weeks in culture, most cells established an apparent polarity, contained well-developed Golgi apparatus and rough endoplasmic reticulum and intermediate filaments, but no pigment granules. A bundle of intermediate filaments was found in the perinuclear cytoplasm. Multilayer cells presented a typical apex-to-apex and base-to-base configuration , and the extracellular material was detected only in the base-to-base intercellular spaces. Our culture system provided differentiated cells derived from the pigment epithelia of human ciliary processes.
Cells, Cultured↗
Ocular responses to leukotriene C4 and D4 in the cat.
The effects of leukotriene C4 (LTC4) and D4 (LTD4) on the iridial smooth muscles, intraocular pressure, blood-aqueous barrier and regional blood flow in the eye have been studied in cats. The test compounds were injected into the anterior chamber. Both LTC4 and LTD4 caused a dose-dependent constriction of the pupil, the agents being about equipotent. The effect on the iridial sphincter muscle was not dependent on nerve conduction, cyclo-oxygenase products or muscarinic receptors. Maximal constriction was achieved with 0.1-1 microgram of the test compounds. The smallest dose to induce a decrease in pupil diameter was 0.01 microgram. After intracameral injection of 4 micrograms the miotic response was markedly delayed. This indicates that in high concentrations LTC4 and LTD4 probably also stimulate the iridial dilator muscle. The blood flow in the anterior uvea decreased after intracameral injection of 4 micrograms LTC4/LTD4. Smaller doses had no clear effect. There was no effect on the blood-aqueous barrier as judged from the aqueous humor protein concentration. The intraocular pressure decreased slightly after injection of the test compounds.
Animals↗
[A new function of the non-pigmented epithelium of ciliary processes in the formation of aqueous humor].
The invagination of the optic vesicle has, as one of its consequences, the apposition of the apices of the nonpigmented and pigmented epithelia of the ciliary processes of the eye. There are well developed intercellular ciliary "channels" formed at the apices of these cells. Embryologically the ciliary epithelia are homologous to the epithelia of the choroid plexus, a characteristically differentiated ependyma. These epithelial cells have a polarity. For example, the supranuclear region of the nonpigmented epithelia has Golgi apparatus. While stimulation of the epithelia of the choroid plexus by beta adrenergics or cholera toxin increases the rate of production of cerebrospinal fluid, similar stimulation of the adenylate complex within the ciliary epithelia decreases aqueous humor production. When the secretory function of the nonpigmented epithelial cell is activated, fluid is probably reabsorbed from the posterior chamber and secreted apically into the intercellular ciliary channels, in accord with cell polarity, thereby reducing net aqueous inflow. The fluid may enter the ciliary stroma thereafter and thus may become part of what may be called "uveal scleral" flow, or in this instance, uveal flow. The anatomy, physiology, and chemistry fit this hypothesis and form the basis for new investigations of a two-way transport across the ciliary epithelia.
Animals↗
Intraocular effects of lipoxygenase pathway products in arachidonic acid metabolism.
Arachidonic acid is metabolized through the lipoxygenase pathways to hydroperoxy acids (HPETEs), hydroxy acids (HETEs), and leukotrienes, derivatives of 5-HPETE. 5-HETE, 12-HETE, 15-HETE, and 15-HPETE were injected intracamerally in rabbits and leukotriene B4 (LTB4), leukotriene C4 (LTC4 and leukotriene D4 (LTD4) were injected intracamerally in guinea pigs, rabbits and cats. The effects on the intraocular pressure, aqueous humour protein and leukocyte concentration as well as pupil diameter were assessed. 5-HETE, 12-HETE, 15-HETE and 15-HPETE did not cause any change in the parameters studied. LTB4 caused a marked accumulation of leukocytes in the aqueous humour of cats and rabbits, and to some extent in guinea pigs. LTC4 and LTD4 were ineffective in guinea pigs and rabbits, but caused an intense long-lasting non-muscarinic miosis in cats. Thus, most of the lipoxygenase products tested showed little activity in the anterior segment of the eye, except LTB4, that caused leukocyte infiltration, and LTC4 and LTD4 that caused miosis in cats.
Animals↗
Forskolin lowers intraocular pressure by reducing aqueous inflow.
Forskolin is a diterpene derivative of the plant Coleus forskohlii that stimulates adenylate cyclase activity without interacting with cell surface receptors. Forskolin lowers the intraocular pressure of rabbits, monkeys, and humans. In rabbits, net aqueous humor inflow decreases, outflow facility remains unchanged, and ciliary blood flow increases. Tolerance to the intraocular pressure lowering effect did not occur in rabbits after topical doses given every 6 hr for 15 days. In vitro forskolin activates adenylate cyclase of crude particulate homogenates prepared from cultured human ciliary epithelia or from dissected ciliary epithelial processes of rabbit or human eyes. This activation is not blocked by timolol. The stimulation of adenylate cyclase by isoproterenol in vitro is potentiated in the presence of forskolin. Forskolin represents a potentially useful class of antiglaucoma agents differing in molecular mechanism of action from previously used drugs.
Adenylyl Cyclases↗