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Biomedical subjects

R F Brubaker

Publications and source records attributed to R F Brubaker.

At least 55 records · Page 3Linked to original sources
PubMed1994

The effect of melatonin on aqueous humor flow in humans during the day.

BACKGROUND: Aqueous humor flow through the anterior chamber of the eye undergoes a circadian cycle. The rate of flow during the day is twice as high as the rate of flow at night. The pineal hormone, melatonin, also undergoes a circadian cycle. Melatonin levels are high at night, whereas aqueous humor flow is low. The authors studied the effect of oral melatonin on aqueous humor flow in humans. METHODS: The effect of melatonin on aqueous humor flow was evaluated in 19 healthy human volunteers in a randomized, masked crossover study with a placebo control. The hormone or placebo was administered orally during the day when endogenous levels of melatonin are low. Aqueous flow was measured by fluorophotometry for 8 hours. RESULTS: The mean rate of flow during melatonin treatment was 2.71 +/- 0.64 microliters/minute (+/- standard deviation). The rate of flow during placebo treatment was 2.80 +/- 0.66 microliters/minute. There is no statistically significant difference between these two rates (P = 0.4). With a sample size of 19, the study has a power of 92% to detect at least a 15% difference in the rate of flow under the two conditions. Measurement of plasma concentration of melatonin in five subjects confirmed that concentrations after oral dosage reached peaks comparable with the normal endogenous nocturnal peaks. CONCLUSIONS: The authors conclude that melatonin concentrations during the day, comparable with plasma concentrations that occur spontaneously during sleep, do not suppress aqueous humor formation. The authors find no support for the idea that plasma melatonin, per se, can suppress aqueous formation or that the circadian rhythm of plasma melatonin is primarily responsible for the circadian rhythm of aqueous humor flow.

Administration, Oral↗
PubMed1994

Aqueous flow in humans after adrenalectomy.

PURPOSE: This study was performed to determine if the circadian rhythm of aqueous humor formation and the aqueous humor suppressing effect of beta-adrenergic antagonists can occur in the absence of adrenally derived epinephrine. METHODS: Twenty-one human subjects who had undergone bilateral adrenalectomy were studied during a 28-hour period. The study was divided into four time periods as follows: morning 1 (8 AM to noon), afternoon (noon to 4 PM), night (midnight to 6 AM), and morning 2 (8 AM to noon). At 6:45 AM before the morning 2 measurements, one drop of 0.5% timolol was applied to one eye and one drop of placebo (artificial tears) was applied to the other eye. Topical fluorescein and a scanning fluorophotometer were used to measure the rate of aqueous humor flow. Twenty normal controls were studied in a similar fashion but did not undergo the morning 2 measurement. RESULTS: In the subjects lacking adrenals, the daytime rates of aqueous flow were 3.17 +/- 0.78 microliters/min (mean +/- SD) and 3.16 +/- 0.67 microliters/min for the morning 1 and afternoon periods, respectively. The rates in daytime periods were not significantly different from each other (P = 0.699). The rate of aqueous flow for the night period was 1.37 +/- 0.37 microliters/min, a 57% reduction from both morning 1 and afternoon periods (P < 0.001). The morning, afternoon, and night rates of flow in normal controls were not significantly different from the rates in subjects lacking adrenals. For the morning 2 period, the aqueous flow was 2.74 +/- 0.54 microliters/min for the placebo-treated eye and 1.77 +/- 0.38 microliters/min for the timolol-treated eye. The rate of aqueous flow was reduced (35%) in the timolol-treated eye when compared to the fellow placebo-treated eye (P < 0.001). The timolol-treated eye also showed a 26% reduction in intraocular pressure when compared to the fellow placebo-treated eye (P < 0.001). CONCLUSION: The study demonstrates that both the circadian rhythm of aqueous flow and the daytime response to timolol persist in the absence of the adrenal glands.

Adrenalectomy↗
PubMed1994

The effect of topical timolol on epinephrine-stimulated aqueous humor flow in sleeping humans.

PURPOSE: It has been shown that intravenously administered epinephrine can increase the rate of aqueous humor flow in sleeping humans. This experiment was conducted to determine if this stimulatory effect can be blocked by the beta-adrenergic antagonist timolol. METHODS: Twenty normal human subjects were studied for one sleep cycle at night. Epinephrine was infused intravenously at a rate of 1 microgram/min. One eye received a single drop of 0.25% timolol, and the fellow eye received a placebo. Aqueous humor flow was measured by the rate of disappearance of fluorescein from the eye. RESULTS: The rate of aqueous humor flow was 14% lower in the timolol-treated eye than in the placebo-treated eye during 6 hours of sleep. This difference was interpreted as being due to blockage of part of epinephrine's effect on aqueous humor flow by topical timolol. CONCLUSION: It was concluded that the effect of systemically administered epinephrine on aqueous humor flow is at least partly mediated locally on the eye and that some portion of timolol's well-known effect on daytime aqueous humor flow could be due to inhibition of the ocular effects of epinephrine.

Administration, Topical↗
PubMed1994

The effect of oral dexamethasone on the circadian rhythm of aqueous humor flow in humans.

PURPOSE: To determine if the circadian rhythm of plasma corticosteroid activity is necessary for the circadian rhythm of aqueous humor flow to occur in humans. METHODS: Twenty normal volunteers were recruited for this randomized, double-masked, placebo-controlled study. Oral dexamethasone was given at a dose of 0.5 mg every 6 hours; this is equivalent to more than two times the normal 24-hour endogenous adrenal corticosteroid production. This dosage schedule will maintain a relatively constant level of corticosteroid action throughout a 24-hour period. Topical fluorescein and a scanning fluorophotometer were used to measure the rate of aqueous humor flow. Subjects were studied on two separate days. On one study day, the subject took 0.5 mg of dexamethasone every 6 hours; on the other study day, the same subject took a placebo every 6 hours. RESULTS: During the morning, aqueous flow was 4.06 +/- 0.70 microliters/min (mean +/- SD) in subjects taking dexamethasone and 3.82 +/- 0.85 in subjects taking a placebo. This 6% higher dexamethasone flow was not significant (P = 0.10). During the afternoon, aqueous flow was 3.83 +/- 0.78 in subjects taking dexamethasone and 3.52 +/- 0.77 in subjects taking a placebo. This 9% higher dexamethasone flow was statistically significant (P = 0.02). The nighttime aqueous flow was 1.38 +/- 0.45 in subjects taking dexamethasone and 1.43 +/- 0.34 in subjects taking the placebo. There was not a significant difference between placebo and dexamethasone during the night (P = 0.40). On each day, intraocular pressure was measured at 8:00 AM, 4:00 PM, and 6:00 AM. When comparing dexamethasone to placebo, no significant difference was observed in any of the intraocular pressures. CONCLUSIONS: The study is interpreted as showing that the reduction of aqueous humor flow during sleep can occur in the absence of a comparable fall in plasma corticosteroid pathway.

Administration, Oral↗
PubMed1993

Aqueous humor dynamics in low-tension glaucoma.

We measured the diurnal aqueous humor flow in patients with low-tension glaucoma by clearance of topically applied fluorescein. Ten patients with low-tension glaucoma participated in the study, and ten age-matched healthy volunteers served as control subjects. The diurnal aqueous humor flow was 2.58 +/- 0.78 microliters/min (mean +/- standard deviation) in the control group and 2.48 +/- 0.61 microliters/min in the low-tension glaucoma group. The corresponding nocturnal data were 0.98 +/- 0.22 microliters/min and 1.24 +/- 0.45 microliters/min. The differences were not statistically significant. Tonographic facility of outflow and intraocular pressure were also measured. There were no statistically significant differences between the two groups in either facility or pressure. No evidence was found in this small group of patients to support the hypothesis that the normal tension in this disease results from a combination of low facility and low flow.

Aged↗
PubMed1993

Effect of desmopressin on aqueous humor flow in humans.

The rate of aqueous humor flow was studied in 17 human subjects with neurogenic diabetes insipidus. Flow was measured by fluorophotometry on two consecutive afternoons. The first day, subjects used desmopressin to control their diuresis; on the second day, subjects did not use desmopressin and had uncontrolled diuresis. On both days, one eye was treated with the beta-adrenergic antagonist, timolol. With desmopressin, the rate of aqueous humor flow in the untreated eye was 2.53 +/- 0.79 microliters/min (mean +/- standard deviation) and in the timolol-treated eye was 1.69 +/- 0.40 microliters/min. Without desmopressin, the rate of aqueous humor flow in the untreated eye was 2.34 +/- 0.69 microliters/min and in the timolol-treated eye was 1.53 +/- 0.43 microliters/min. Thus, the use of desmopressin was associated with a slightly higher rate of aqueous humor flow in both the normal and the beta-adrenergically inhibited eye (P = .05), and the suppression of aqueous humor flow associated with beta-adrenergic inhibition occurred with and without antidiuretic hormone (P < .001). The observed differences in aqueous humor flow on the two days could have been caused by a direct effect on the eye or to indirect effects, such as the change in plasma osmolality, which changed from 291 +/- 6 mOsm on the desmopressin day to 299 +/- 8 mOsm on the desmopressin-abstention day (P < .001).

Administration, Intranasal↗
PubMed1993

The effects on aqueous dynamics of PhXA41, a new prostaglandin F2 alpha analogue, after topical application in normal and ocular hypertensive human eyes.

OBJECTIVE: To study the effects of a topically applied prostaglandin F2 alpha analogue, PhXA41 (Latanoprost; 13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F2 alpha-isopropyl ester), on aqueous dynamics in the human eye. DESIGN: A randomized, double-masked study was carried out on 20 normal and 20 ocular hypertensive humans. One eye of each subject was treated with 0.006% PhXA41, while the contralateral eye received placebo twice daily for 5 days. MAIN OUTCOME: Compared with placebo, PhXA41 reduced intraocular pressure in both groups by approximately 20%. RESULTS: Tonographic facility of outflow was increased 24% in the normal group and 30% in the ocular hypertensive group; no changes were observed in the rates of aqueous humor flow in either group. The changes in tonographic facility were insufficient to fully explain the ocular hypotensive effect of the drug, suggesting that PhXA41 enhances outflow via the uveoscleral pathway. The suitability of fluorophotometry as a measure of flow was confirmed by three methods of comparing blood-aqueous barrier permeability: polarization of cameral fluorescence, intensity of backscattered light from the anterior chamber (flare), and cameral fluorescence after oral administration of fluorescein sodium. All of these measured parameters were normal, suggesting that this compound has no clinically significant effects on the blood-aqueous barrier or on the accuracy of fluorophotometry. PhXA41 was well tolerated in both groups. Only four of 40 subjects reported a transient foreign-body sensation, and only one of 40 subjects was observed to have greater than moderate conjunctival hyperemia. Most subjects had no symptoms and no measurable hyperemia. CONCLUSIONS: These results suggest that PhXA41 is a potentially useful ocular hypotensive agent that enhances the egress of aqueous humor via both major outflow pathways. The relative lack of ocular side effects in this study further suggests that this agent has promise for the treatment of chronic glaucoma.

Aqueous Humor↗
PubMed1993

A simple three-compartment model of anterior segment kinetics.

Diffusion of fluorescein between the plasma and anterior chamber has been considered a one-step process with transfer coefficient kd. However, after systemic administration, fluorescein enters the anterior chamber by a different kinetic than this simple model predicts. In this study we added to the model another compartment, the 'iris', between the plasma and anterior chamber. When fluorescein diffuses into the anterior chamber, it must cross two barriers, one between plasma and iris with coefficient ki.ip, and one between iris and anterior chamber with coefficient ki.ia. Fluorescein was measured in the anterior chamber after intravenous injection and was compared to fluorescein concentration calculated by using both kinetic models, the three-compartment model (iris, anterior chamber, and cornea) and the two-compartment model (anterior chamber and cornea). Transfer coefficients were determined by the method of least squares in 12 pigmented rabbits and two groups of six human subjects measured in two previous fluorophotometry studies. In all subjects except one, the three-compartment model matched the data better than the two-compartment model. In a second experiment, diffusion of fluorescein out of the anterior chamber was studied in 15 pigmented rabbits. Diffusional loss was determined from the relative clearances of rhodamine-labeled dextran, a large molecule that left only by bulk outflow, and fluorescein that was cleared by diffusion and outflow. The upper 95% confidence limit of diffusional clearance was less than 11% of total clearance in anesthetized rabbits.

Animals↗
PubMed1993

A comparison of two methods of measuring aqueous flow in humans: fluorophotometry and flare measurement.

The technique of Anjou and Krakau for measuring flare and Krakau's method for estimating aqueous humor flow in humans was compared to the fluorophotometric procedure of Jones and Maurice. The precision of flare was measured in 20 normal human volunteers, and the precision of flow was measured with fluorophotometry in 24 volunteers. In addition, the circadian rhythms of both flow and flare were measured simultaneously in a separate group of 20 subjects. This simultaneous measurement allowed us to calculate the entry rate of scattering substances into the aqueous humor as a function of time of day. This entry rate is critical for measuring flow by the method of Krakau. The mean coefficient of variation (+/- SD) of repeated measurements of flare at the same time of day was 23.2% +/- 10.3%. The mean coefficient of variation of the measurement of aqueous flow by fluorophotometry was 15.9% +/- 8.2%, significantly better than the measurement of flare (p = 0.01). The daytime entry rate of scattering substances into the aqueous humor varied from 1.39 +/- 0.86 microgram/min (calculated as albumin) to 1.05 +/- 0.58 microgram/min. The rates in daytime hours were not significantly different from each other. At night during sleep, the entry rate was 0.67 +/- 0.48 microgram/min, significantly slower (p between 0.002 and < 0.001). These data indicate that the flare technique cannot be used alone to calculate the circadian rhythm of flow and that direct measurement of flow by fluorescein clearance is likely to be the most repeatable and accurate of the two.

Aqueous Humor↗
PubMed1993

Aqueous humor flow and flare in patients with myotonic dystrophy.

PURPOSE: Myotonic dystrophy is an autosomal dominant form of muscular dystrophy associated with a mutation that affects a gene on chromosome 19. Extremely low intraocular pressure is one of a constellation of clinical signs that sometimes accompany this disorder. This study was performed to determine if the ocular hypotony can be explained by aqueous humor hyposecretion. METHODS: Seventeen persons with myotonic dystrophy and seventeen age-matched controls were studied. Intraocular pressure, light scattering (flare), fluorescein clearance at various times of day, and the response of the eye to the topical timolol were measured. RESULTS: Intraocular pressure was 40% lower in the persons with myotonic dystrophy (8.4 mm Hg vs 14.0 mm Hg) and flare was 50% higher (55.8 mg/dl albumin equivalent vs 37.1 mg/dl albumin equivalent). Fluorescein clearance in persons with myotonic dystrophy was indistinguishable from normal at all times of day. Myotonic eyes responded normally to topical timolol. The physiological data of this study are most consistent with the conclusion that the rate of aqueous humor flow is reduced approximately 9%, and the rate of inward leakage of light scattering proteins is increased approximately 37% in well-established myotonic dystrophy with ocular hypotony. CONCLUSIONS: The reduced aqueous humor flow alone is insufficient to explain the ocular hypotony. We hypothesize that the hypotony is due primarily to atrophy of the ciliary muscle that increases fluid exchange between the anterior chamber and the anterior uvea with consequent enhancement of uveoscleral outflow.

Administration, Topical↗
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↗