Biomedical subjects

R F Brubaker

Publications and source records attributed to R F Brubaker.

At least 19 recordsLinked to original sources

PubMed1992

Aqueous dynamics in exfoliation syndrome.

Eighteen untreated patients with unilateral exfoliation syndrome without glaucoma were studied with regard to differences in aqueous dynamics between the affected and unaffected fellow eyes. Additionally, both eyes of the patients with exfoliation were compared to the eyes of 18 age-matched and gender-matched control subjects. Intraocular pressure was significantly higher (13.9 +/- 3.0 mm Hg [mean +/- standard deviation]) in the affected compared with the unaffected eyes (12.2 +/- 2.5 mm Hg), but no difference in aqueous humor flow was detected when eyes in the three groups were compared (affected eyes, 2.40 +/- 0.60 microliter/min; unaffected eyes, 2.40 +/- 0.65 microliter/min; control eyes, 2.61 +/- 0.60 microliter/min). Anterior chamber volumes were significantly smaller in affected (122 +/- 37 microliters) and unaffected eyes (121 +/- 37 microliters) of the patients with exfoliation compared with the eyes of the control subjects (145 +/- 30 microliters). Apparent resistance was higher in the eyes with exfoliation (6.5 +/- 1.9 min mm Hg/microliters) compared with both unaffected (5.4 +/- 1.2 min mm Hg/microliters) and control groups (5.2 +/- 1.8 min mm Hg/microliters), although these differences were not statistically significant.

Aged↗

PubMed1992

Progression and regression of partial corneal involvement in the iridocorneal endothelial syndrome.

We observed three women with partial corneal involvement in the iridocorneal endothelial syndrome for more than ten years. During this time, the peripheral anterior synechiae progressed in all three, with one patient developing glaucoma. In two patients, the abnormal endothelial cells spread to cover the entire posterior corneal surface; in the third, they disappeared almost entirely. The endothelial permeability to fluorescein remained abnormally low only in the two eyes with diffusely abnormal endothelium, and increased to normal in the third eye as the abnormal endothelium disappeared. The permeability in the third eye had been abnormally low only in the superior half of the cornea, where the abnormal endothelium was located. As the abnormal endothelium regressed, it was replaced by normal endothelium with a normal cell density similar to that of the unaffected fellow eye. Thus, for more than ten years, the partial endothelial involvement associated with the iridocorneal endothelial syndrome progressed substantially in two patients and regressed dramatically in a third.

Adult↗

PubMed1992

Acetazolamide but not timolol lowers aqueous humor flow in sleeping humans.

The effect of timolol, acetazolamide, and the combination of the two drugs on the rate of aqueous formation in 18 healthy human subjects was measured during the day and at night in a placebo-controlled, double-masked, randomized study. In the absence of any drugs, aqueous flow during the day was 2.61 +/- 0.82 (mean +/- SD) microliters/min and at night, 1.08 +/- 0.59, a 59% lower flow rate when compared with the daytime value (P < 0.0001). When compared with these aforementioned control values, timolol alone reduced the rate of aqueous flow by 39% (P < 0.0001) in awake subjects but had no statistically significant effect on the flow rate in sleeping subjects (P = 0.33). Acetazolamide alone reduced aqueous flow during the day by 21% compared with the control flow rate (P = 0.02) and at night by 24% below the nocturnal flow rate in the sleeping eye (P = 0.04). The combination of the two drugs reduced flow during the day by an additional 13% (P = 0.024) compared with the flow rate achieved by timolol alone, and by an additional 32% (P < 0.0001) compared with the flow rate reduction attained by acetazolamide alone. There was no statistically significant difference in the nocturnal flow rates achieved by acetazolamide alone or in combination with timolol (P = 0.37). These data confirm previous studies demonstrating the effect of timolol, acetazolamide, and sleep on the rate of aqueous humor formation. Unlike a previous study, it was found that acetazolamide lowers the aqueous flow below the already low nocturnal flow rate that occurs spontaneously in the sleeping eye.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗

PubMed1992

Progression and regression of partial corneal involvement in the iridocorneal endothelial syndrome.

We have observed three women with partial corneal involvement in the ICE syndrome for over 10 years. During this time, the peripheral anterior synechiae progressed in all three, with glaucoma developing in one patient. In two patients, the abnormal endothelial cells spread to cover the entire posterior corneal surface; in the third, they disappeared entirely (ie, "the ICE melted"). The endothelial permeability to fluorescein remained abnormally low only in the two eyes with diffusely abnormal endothelium, increasing to normal in the third eye as the abnormal endothelium disappeared. The permeability in that eye had been abnormally low only in the superior half of the cornea, where the abnormal endothelium was. As the abnormal endothelium regressed, it was replaced by normal endothelium with a normal cell density similar to that of the opposite, uninvolved eye. Thus, over a 10-year period the partial endothelial involvement associated with the ICE syndrome progressed substantially in two patients and regressed dramatically in a third.

Adult↗

PubMed1992

Intravenous epinephrine stimulates aqueous formation in the human eye.

An experiment was done to determine if intravenously administered epinephrine would stimulate the rate of aqueous humor flow in sleeping human subjects. Twenty normal volunteers participated in a double-masked randomized placebo-controlled study. The rate of aqueous humor flow was measured by the rate of clearance of topically applied fluorescein. Measurements were made on two separate nights while the subjects slept, once during a placebo infusion and again during an intravenous infusion of epinephrine (rate, 1 microgram/hr; a rate calculated to be threefold the basal adrenal secretion in supine sedentary human subjects). Compared with placebo, epinephrine infusion had no effect on the blood pressure of sleeping subjects, increased the heart rate by 10%, and increased aqueous flow by 27%. Systolic blood pressure was 112 +/- 9 mmHg (mean +/- standard deviation) during placebo infusion and 114 +/- 13 during epinephrine infusion. The heart rate was 60 +/- 10 beats/min during placebo and 67 +/- 14 during epinephrine infusion (P = 0.011). Aqueous flow was 1.11 +/- 0.51 microliters/min during placebo and 1.42 +/- 0.52 during epinephrine infusion (P = 0.016). It was concluded that adrenal medullary secretion can stimulate aqueous formation and may explain in part the circadian rhythm of aqueous flow.

Adrenal Medulla↗

PubMed1992

Computerized analysis of pupillograms in studies of alertness.

When alert subjects sit in a quiet, darkened room for 10-15 min, their pupils remain dilated. If the subjects become sleepy or fatigued, their pupils become miotic and oscillate. Pupillometry, the recording of pupil diameter, has been used to study alertness. Pupillograms are typically graded by subjective assessment on the basis of oscillations of pupil diameter (hippus) and miosis. In this study, numeric parameters were calculated from pupillograms and were compared to subjective ratings by clinicians. Pupil diameters were recorded for 15 min at five samples per second with a custom built video pupillometer. Subjects sat in the dark and fixated a small red light. Digital filtering techniques and Fourier analysis were used to calculate several parameters designed to report hippus and miosis. The same set of pupillograms was graded by three physicians familiar with pupillometry. Grades were assigned on a scale of 1 to 4, 1 being most alert and 4 least alert. A linear combination of three of the numeric parameters had the highest correlation with the average subjective grade (r = 0.92). These techniques provide a quantitative way to evaluate pupillograms that will be used in the assessment of alertness.

Adolescent↗

PubMed1992

A study of aqueous humor formation in patients with cystic fibrosis.

The circadian pattern of aqueous formation and the effect of timolol on aqueous flow was studied in 12 patients with cystic fibrosis. Cystic fibrosis is a disease characterized by a defect in a chloride channel-associated regulatory protein found in epithelial cells. Improper regulation of these chloride channels, causes abnormal composition of exocrine secretions, including respiratory tract, gastrointestinal tract, exocrine pancreas, and sweat glands. Ocular findings previously reported include abnormal endothelial cell permeability, decreased tear secretion, and abnormal tear composition. In this study, aqueous humor flow was measured by fluorophotometry. No statistically significant difference was found when flow rates measured during the morning, during the afternoon, at night, and after topical timolol treatment were compared to normal values. The conclusion is that the beta adrenergically regulated chloride selective channels defective in patients in cystic fibrosis do not play a major role in the formation of aqueous humor or they are not regulated by the cystic fibrosis transmembrane conductance regulator (CFTR).

Administration, Topical↗

PubMed1991

Apraclonidine and timolol. Combined effects in previously untreated normal subjects.

Twenty healthy subjects were tested for the aqueous-suppressing effects of the alpha 2-adrenergic agonist apraclonidine hydrochloride. Apraclonidine caused a 30% reduction of mean (+/- SD) aqueous flow during the daytime from 2.84 +/- 0.61 microL/min, similar to what has been observed for beta-adrenergic antagonists. Apraclonidine, like acetazolamide and unlike timolol maleate, was able to suppress the aqueous flow of sleeping subjects below the spontaneous nocturnal rate of 1.15 +/- 0.40 microL/min to 0.84 +/- 0.28 microL/min, a 27% change. When apraclonidine and timolol were given together in the daytime, no clinically significant or statistically significant additive effect was observed. The range of flows with either drug alone or the combination of the two measured from 2 to 4 PM was 1.41 to 1.78 microL/min. This result contrasts with studies of the effect of apraclonidine on patients who have received long-term beta-blockers where an additive effect is observed. The lack of an additive effect on flow in previously untreated normal subjects suggests that the two drugs act at least in part via a common pathway.

Administration, Topical↗

PubMed1991

Topical flurbiprofen pretreatment does not block apraclonidine's effect on aqueous flow in humans.

Flurbiprofen's effect on the ability of apraclonidine hydrochloride (para-aminoclonidine) to reduce aqueous humor flow was studied in 20 healthy human volunteers. Flurbiprofen sodium, in a 0.03% concentration, was administered topically to one eye and a placebo to the contralateral eye of each subject in a random, double-masked fashion. A total of four drops was administered to each eye during a 30-minute period beginning at 7 AM. Thirty minutes later, one drop of 1% apraclonidine was instilled into each eye. Flow rates were measured with fluorophotometry from 7 AM to noon. The mean (+/- SD) rate of flow after administration of flurbiprofen and apraclonidine at the peak of apraclonidine's effect was 1.56 +/- 0.50 microL/min, and after administration of placebo and apraclonidine was 1.53 +/- 0.43 microL/min. With a sample size of 20 and a coefficient of variation of flow measurement of 15%, there is a 95% chance of detecting a difference in flow rate of 15% or greater using the techniques employed in this study. Since there was no statistically significant difference between the rates of flow under the two conditions, we conclude that flurbiprofen has no appreciable effect on apraclonidine's ability to suppress aqueous flow.

Administration, Topical↗

PubMed1991

Effect of apraclonidine in long-term timolol users.

A double-blind, randomized study was undertaken to determine if the alpha-agonist apraclonidine has an additive effect in eyes treated with long-term timolol. Seventeen patients (15 with primary open-angle glaucoma, 1 with pigmentary glaucoma, and 1 glaucoma suspect) on long-term timolol treatment in both eyes received a single dose of apraclonidine in one eye and a placebo in the other. Aqueous flow and intraocular pressure were compared in the treated and untreated eyes. There was no statistically significant difference in pretreatment aqueous flow between the two eyes. When flow in the apraclonidine-treated eyes (1.39 +/- 0.41 microliter/min, mean +/- standard deviation) was compared with that of the untreated eyes (1.66 +/- 0.38 microliter/min), a statistically significant difference was found (P less than 0.01). Apraclonidine reduced intraocular pressure by 1.3 mmHg (P = 0.05). The implications of these findings on the understanding of the mechanism of action of adrenergic drugs in the human eye is discussed.

Adrenergic alpha-Agonists↗

PubMed1991

The correlation between serum progesterone and aqueous dynamics during the menstrual cycle.

Exogenously-administered progesterone has been shown to lower intraocular pressure. However, attempts to correlate endogenous progesterone levels and aqueous dynamics have produced inconsistent results. In this study, 20 healthy, non-pregnant women were followed over a 28-day menstrual cycle. Serum progesterone level, intraocular pressure, and aqueous flow rate were measured weekly. We were unable to demonstrate any correlation between progesterone levels and either aqueous flow or intraocular pressure.

Adult↗

PubMed1991

Flow of aqueous humor in humans [The Friedenwald Lecture].

Based on clinical experiments with fluorophotometry, several observations can be made about aqueous flow through the chambers of the human eye. 1. The rate of flow is 2.75 +/- 0.63 microliters/min in normal subjects, as derived from measurements averaged during normal office hours. The normal range (95%) is 1.8 to 4.3 microliters/min. 2. There is a circadian rhythm of flow, with the highest rates during morning hours, slightly lower rates during afternoon hours, and rates during sleep that are approximately one half of those during the morning. The hormonal basis for this rhythm is unknown, but it is known to be present in both eyes of persons with unilateral Horner's syndrome. 3. A slight decline of the rate occurs after age 10 yr--3.2% per decade. There is no significant difference in aqueous flow between men and women. 4. Of the hundreds of drugs that are used clinically, most are unlikely to have a significant effect on aqueous flow. Exceptions are the beta-adrenergic agonists that, under certain circumstances, are able to increase flow, the corticosteroids that may have a stimulating effect on flow, and three classes of drugs that have therapeutically useful suppressing effects on flow: carbonic-anhydrase inhibitors, beta-adrenergic antagonists, and alpha 2-selective adrenergic agonists. 5. Timolol, which has a remarkably consistent suppressing effect on flow during the day, has no effect on the flow of sleeping subjects. By contrast, acetazolamide and apraclonidine are able to reduce the flow of sleeping subjects. 6. Acute doses of beta-adrenergic antagonists and alpha 2-agonists are not additive, but beta-adrenergic antagonists and carbonic-anhydrase inhibitors are partly additive. 7. The eye adapts partly to the chronic use of timolol and recovers from its effects when it is discontinued. 8. The rate of disappearance of the effect of beta-adrenergic antagonists is longer for the noncardioselective agents, such as timolol and levobunolol, but is relatively short for the cardioselective agent, betaxolol. 9. The rate of aqueous flow is insensitive to moderate changes of intraocular pressure. Clinical studies can provide suggestive leads for more basic investigations or test specific hypotheses. Biochemical, biologic, and pharmacologic approaches in simpler, more controlled experimental conditions are necessary to determine the fundamental processes that bring about aqueous formation in the living eye. The combination of many disciplines (eg, studying molecules, cells, tissues, organs, and the intact living system) has the best chance of furthering our understanding of the aqueous circulation.

Animals↗

PubMed1991

The nocturnal suppression of aqueous humor flow in humans is not blocked by bright light.

Normal human subjects were studied hourly by fluorophotometry to measure the normal circadian rhythm of aqueous humor flow. On a separate day, the subjects slept for approximately 1 hr after lunch; this short nap was not found to have any effect on aqueous flow. On a separate night, the subjects slept under a bright light of 2500 lux; the light was not found to have any effect on flow in the sleeping subjects. Because bright light blocks melatonin release in humans, nocturnal suppression of aqueous flow in humans may not be driven by systemic melatonin release.

Aqueous Humor↗

PubMed1991

Effect of chronic epinephrine on aqueous humor flow during the day and during sleep in normal healthy subjects.

Epinephrine 2% drops were administered to one eye and a placebo to the fellow eye twice a day for 2 weeks in 18 normal human volunteers. The circadian rhythm of aqueous humor flow was measured by fluorophotometry. Epinephrine (compared with placebo) had no measurable effect on the rate of aqueous flow or the circadian rhythm of aqueous humor flow. These results suggest either that topical application of epinephrine cannot achieve a sustained effect on the mechanism of aqueous formation compared with endogenous epinephrine or that circulating epinephrine is not the sole or principal hormonal messenger that mediates the circadian rhythm of aqueous flow in humans. An experiment in which epinephrine was administered systemically might clarify this ambiguity.

Aqueous Humor↗

PubMed1990

The fluorescent indicator pyranine is suitable for measuring stromal and cameral pH in vivo.

Three pH-sensitive fluorescent indicators (fluorescein, bis-carboxyethyl-carboxyfluorescein and pyranine) were studied to determine their usefulness as probes for the living cornea and anterior chamber. Of the three dyes, pyranine had properties which render it almost ideally suited for this purpose. Adequate concentrations are reached in the cornea and anterior chamber after topical administration; measurements can be made by fluorophotometry for many hours. The pH is calculated by measuring the ratio of fluorescent intensity at two excitation wavelengths, I463/I404, a measurement which is dependent on pH but independent of the concentration of the fluorophore and other variables which can alter the intensity. In the rabbit eye, pyranine in the cornea and anterior chamber was observed to undergo easily measurable changes in fluorescent ratios associated with lid closure and contact lens wear, indicating its sensitivity to mild changes in pH.

Albumins↗

PubMed1990

Rate of flow of aqueous humor determined from measurements of aqueous flare.

Measurement of light scattered in the anterior chamber can provide important clinical information about the eye. In this study, a scanning ocular spectrofluorophotometer was used to measure scattering in the anterior chamber. Pathologic scattering (flare) was induced by argon laser photocoagulation of the iris in pigmented rabbits. The spectrally corrected intensity of the flare in inflamed eyes decreased as the inverse 2.2 power of the wavelength of the illuminating beam. The strongest signal with this instrument was measured at 470 nm. Diurnal variation of normal and spontaneous scatter from the aqueous humor was measured in nine pigmented rabbits entrained to a 12-hr light/12-hr dark cycle and in eight human subjects. A technique is described for determining the rate of flow of aqueous humor from scattered light when the transfer rate of scattering substance into the anterior chamber is constant. This technique was used to study changes in flow over the diurnal cycle. The rate of flow in human subjects during sleep was 60% of the rate during waking hours. In rabbits, the rate was lowest (44% of maximum) during the 6 hr after the lights were turned on, and were greatest just before the lights were turned on. These findings confirm previous studies of the circadian rhythm of aqueous humor flow in rabbits and humans.

Animals↗

PubMed1979

Use of air to decrease endothelial cell loss during intraocular lens implantation.

We performed 26 consecutive intracapsular cataract extractions with lens implantation. The last 17 implantations were performed with air instilled in the anterior chamber, whereas the first nine operations were performed without air. The central corneal endothelium of each eye operated on was photographed before and within five days after lens implantation. A computer analysis of the endothelial photographs showed that, on the average, 32% of the central corneal endothelial cells were lost during lens implantation without the use of air and 15% were lost when the lens was implanted with air. Increased endothelial cell loss was significantly correlated with the failure to implant the lens with use of air, with increased operative endothelial trauma, and with higher postoperative intraocular pressures. A significantly larger increase in corneal thickness on the first postoperative day occurred in patients with larger or more varied cell sizes preoperatively.

Air↗

PubMed1979

Effect of timolol on the permeability of corneal endothelium.

The effect of short-term administration of timolol on the permeability of the corneal endothelium to fluorescein was measured in normal subjects (single drop) and in a small group of glaucoma patients (one week's treatment). No effect on the endothelium was found in the normal eyes. In the glaucomatous eyes, endothelial permeability was higher than normal when measured after one week without topical medications and normal when measured after one week on timolol treatment. No evidence was found that short-term administration of this drug disturbs the barrier function of the endothelium.

Adult↗