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Biomedical subjects

J E Grunwald

Publications and source records attributed to J E Grunwald.

At least 19 recordsLinked to original sources

The acute effect of oral acetazolamide on macular blood flow.

Acetazolamide has been shown to be beneficial in the treatment of macular edema. To investigate whether this effect is associated with changes in the retinal circulation, the acute effect of oral acetazolamide on macular blood flow was studied in 20 healthy volunteers. The blue-field simulation technique, a noninvasive method enabling the quantitation of the number (N) and mean velocity (Vm) of leukocytes flowing in the subject's own macular capillaries was used in this study. On two different occasions, separated by 3 or more days, 20 subjects adjusted Vm and N of computer-simulated leukocytes moving on a video screen to match those of their own entoptically perceived leukocytes before and 3 hr after a double-blind, randomized administration of 500 mg acetazolamide or placebo capsules. Ten trials were done, and the velocities were averaged. After acetazolamide ingestion, there was a nonsignificant average change from baseline in Vm (2.5 +/- 23% [+/- one standard deviation]; P greater than 0.1, by paired student t-test) and N (6.9 +/- 25%, P greater than 0.1). After placebo ingestion, the average changes from baseline in Vm and N also were not statistically significant (-1 +/- 18% and 14.9 +/- 30.3%, respectively). Furthermore, when compared with the changes measured after placebo intake, acetazolamide ingestion was associated with a nonsignificant 4.3 +/- 28.7% change in Vm (P greater than 0.1) and a -8 +/- 30.9% change in N (P greater than 0.1). With 20 subjects tested, the calculated average minimum change in leukocyte velocity that could have been detected with this technique (P less than 0.05, by paired student t-test) is about 9%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide

Effect of topical carteolol on the normal human retinal circulation.

The effect of topical carteolol 1%, a beta-adrenergic blocker with intrinsic sympathomimetic activity, on the retinal circulation was investigated in 15 normal subjects using laser Doppler velocimetry and monochromatic fundus photography. In a double-masked randomized design, one eye received one drop of carteolol 1% and the fellow eye one drop of placebo. Vessel diameter, maximum erythrocyte velocity, and volumetric blood flow rate were determined in a major temporal vein of each eye just before instillation of the drops and then 120 min later. No significant changes in heart rate or mean brachial artery blood pressure were detected after treatment. Intraocular pressure decreased by 28% in the carteolol-treated eye (P less than 0.0001) and by 15% in the placebo-treated eye (P less than 0.001). No significant changes in vessel diameter, maximum erythrocyte velocity, and volumetric blood flow rate were observed in the carteolol-treated eyes (0.3%, 4.3%, and 3.6%, respectively) or the placebo-treated eyes (0.5%, 5.8%, and 6.7%, respectively).

Administration, Topical

The acute effect of topical epinephrine on macular blood flow in humans.

The acute effect of topical epinephrine HCl 2% on macular capillary blood flow was studied in 18 healthy human volunteers using the blue-field simulation technique. This technique provides a method for quantifying the velocity of leukocytes flowing in macular capillaries. Subjects adjusted the velocity of simulated leukocytes on a computer screen to match that of their own entoptically perceived leukocytes before instilling the drug and 2 hr thereafter. An artificial tear solution was instilled into the fellow eye for a control. Epinephrine instillation resulted in a 8% increase in macular leukocyte velocity and presumably blood flow (P less than 0.03, paired student t-test).

Administration, Topical

Total retinal volumetric blood flow rate in diabetic patients with poor glycemic control.

Total retinal volumetric blood flow rate was measured in 12 normal subjects and 18 poorly controlled diabetic patients with background diabetic retinopathy. Maximum or center-line erythrocyte velocity (Vmax) was assessed by bidirectional laser Doppler velocimetry in four to five major retinal veins of one eye of each subject. Venous diameter (D) was measured from monochromatic fundus photographs. Total venous cross-section and measured total retinal volumetric blood flow in the diabetic patients were significantly larger than normal (P = 0.001 and P = 0.02, respectively). A positive linear correlation was found between Vmax and D in normal and diabetic eyes. Volumetric blood flow rate, Q, varied with D at a power of 2.87 in normal eyes. Total volumetric blood flow correlated with total venous cross-section. It was found that Q in the temporal retina was significantly larger than in the nasal retina in normal subjects (P = 0.0008) and diabetic patients (P = 0.0002). A significant difference in Q was observed between the superior and inferior retina in diabetic patients (P = 0.03) but not in normal subjects. The retinal vascular regulatory response to 100% oxygen breathing was reduced (P = 0.019) in diabetic patients and correlated with the level of background diabetic retinopathy. A close estimate of total volumetric blood flow may be obtained from blood flow measurement in one major retinal vein and the determination of total venous cross-section. This may be important for clinical studies in which measurements of all individual retinal veins may not be feasible.

Adolescent

Successful foscarnet therapy for cytomegalovirus retinitis in an AIDS patient undergoing hemodialysis: rationale for empiric dosing and plasma level monitoring.

Foscarnet is an investigational antiviral agent that has been used effectively in the treatment of cytomegalovirus (CMV) retinitis in AIDS patients. However, it has not been readily available to AIDS patients with renal insufficiency because its major side effect is nephrotoxicity. In this report, the efficacy, safety, and dosing requirements of foscarnet in a hemodialysis-dependent patient with CMV retinitis are presented. Foscarnet was administered for 14 weeks, at an initial dosage of 60 mg/kg after each dialysis session. Plasma concentrations were monitored weekly, and the dosage was adjusted to maintain peak plasma levels in the range of 500-800 microM. Although some laboratory abnormalities occurred (a preexisting anemia continued, serum calcium and phosphorus decreased, and ionized calcium increased), they did not limit therapy. Foscarnet is a potentially useful alternative treatment for CMV retinitis in hemodialysis-dependent AIDS patients.

Acquired Immunodeficiency Syndrome

The effect of caffeine on the human macular circulation.

The acute effect of caffeine on the retinal circulation was studied in 14 healthy volunteers using the blue field simulation technique, which provides measurements of the velocity of leukocytes flowing within the macular capillaries. Subjects adjusted the mean velocity (Vm) of computer-simulated leukocytes moving on a cathode ray tube screen to match that of their own entoptically perceived leukocytes before and 1 hr after a double-masked, randomized administration of 200 mg caffeine or placebo. Caffeine produced an average 13% +/- 5% (SEM) decrease in Vm (P less than 0.05) and a 9% +/- 3% increase in diastolic blood pressure (P less than 0.05). The decrease in Vm and, presumably, blood flow occurring despite the increased diastolic blood pressure probably is attributable to retinal vasoconstriction. This effect may result from caffeine's known inhibitory effect on adenosine, a potent vasodilator of the retinal vasculature.

Adult

Effect of two weeks of timolol maleate treatment on the normal retinal circulation.

The effect of 2 weeks of topical treatment with timolol maleate 0.5% ophthalmic solution on the retinal circulation was investigated using bidirectional laser Doppler velocimetry and monochromatic fundus photography. Fifteen normal healthy volunteers were included in this study. In a double-masked, randomized design one eye of each received one drop of timolol maleate 0.5% twice daily for 14 days, and the fellow eye received placebo. Vessel diameter (D), maximum erythrocyte velocity (Vmax), and volumetric blood flow rate (Q) were determined in one major retinal vein of each eye before treatment, and then, 2 hr after the instillation of drops on the morning of the 15th day of treatment. After treatment, the average change from baseline in D (+0.7%), Vmax (-8.2%) and Q (-7.7%) were not statistically significant in the placebo-treated eyes. In the timolol-treated eyes, the average increase from baseline in D (+0.1%) and Q (+10%) were not statistically significant. Average Vmax, on the other hand, increased significantly from baseline (P less than 0.05) by 9.6%. In comparison to the placebo-treated eyes, Vmax and Q were significantly increased in the timolol-treated eyes (P less than 0.0005 and P less than 0.01, respectively). These results are similar to those reported previously in a study of the effect of a one-time instillation of timolol and, therefore, suggest that the effect of timolol on the retinal circulation is maintained over a 2-week period.

Administration, Topical

Effect of timolol maleate on the retinal circulation of human eyes with ocular hypertension.

We studied the effect of topical timolol maleate 0.5% on the retinal circulation of eyes with ocular hypertension using laser Doppler velocimetry and monochromatic fundus photography. Patients with ocular hypertension had normal eye examinations and had documented elevated intraocular pressures of 23 mmHg or higher on two or more separate occasions. In a double-masked randomized design, one eye of each subject received timolol maleate 0.5% and the fellow eye received placebo. Vessel diameter, maximum velocity of red blood cells, and volumetric blood flow rate were determined in a major retinal vein of each eye just prior to the instillation of drops, and then 2 hr later. In comparison to the baseline value, there was an increase of 12.0% in average red blood cell velocity (P less than 0.005, statistically significant) and of 8.4% in volumetric blood flow rate in the timolol-treated eyes (P less than 0.05, statistically significant). No significant changes in these quantities were observed in the placebo-treated eyes. Also, no significant change in venous diameter was detected in the placebo- and the timolol-treated eyes. In comparison to the baseline, a significantly larger increase in red blood cell velocity was observed in the timolol-treated eyes than in the placebo-treated eyes (P less than 0.05). The difference between the increase in blood flow observed in the timolol-treated eyes and the placebo-treated eyes achieved a probability value of P = 0.058. The increase in blood flow observed in the timolol-treated eyes may be related to the increase in perfusion pressure produced by this drug.

Administration, Topical

Diabetic glycemic control and retinal blood flow.

The effect of strict glycemic control on retinal volumetric blood flow rate (Q) was investigated in 13 insulin-dependent diabetic patients with laser Doppler velocimetry and monochromatic fundus photography. Strict glycemic control was achieved by glucose monitoring and four daily insulin injections. Q was determined in a major retinal vein at baseline and then 5 days, 2 mo, and 6 mo after the institution of strict control. Level of retinopathy was assessed from stereocolor fundus photographs taken at baseline and 6 mo. After 6 mo of strict diabetic control, five eyes demonstrated progression (P) by one or more retinopathy levels, and eight eyes showed no progression (NP). At 5 days, there was a significant decrease in Q of 1.4 +/- 0.9 microliters/min (P less than 0.005) in NP eyes and a nonsignificant increase in Q of 1.2 +/- 1.7 microliters/min in P eyes. Changes in Q from baseline observed at 5 days were strongly correlated with changes in retinopathy level at 6 mo (r = 0.79, P less than 0.005). No significant changes in Q from baseline were observed at 2 and 6 mo. A lack of decrease in Q at 5 days was associated with the progression of retinopathy that occurs in some patients after the institution of strict glycemic control and may serve as a predictor for progression of retinopathy.

Adult

Retinal blood flow regulation and the clinical response to panretinal photocoagulation in proliferative diabetic retinopathy.

Bidirectional laser Doppler velocimetry and monochromatic fundus photography were used to investigate retinal hemodynamics before and after panretinal photocoagulation (PRP) in 25 eyes of 23 diabetic patients with proliferative retinopathy. After PRP, there was a significant decrease in retinal volumetric blood flow rate and an increase in the retinal vascular regulatory response to hyperoxia (R). A significant association was found between the presence or absence of regression of neovascularization and the increase or decrease in R after PRP. Eyes that showed regression of neovascularization had significantly larger average R after PRP than eyes that did not show regression. Lack of improvement in R after PRP may be related to the presence of remaining ischemia or hypoxia in eyes that continue to show proliferation after PRP.

Adult

Effect of topical timolol maleate on the ophthalmic artery blood pressure.

The effects of topical timolol maleate 0.5% on the ophthalmic artery diastolic (OABPd), systolic (OABPs) and mean blood pressure (OABPm) were investigated in 19 healthy subjects using compression ophthalmodynamometry. In a randomized, double-blind study, one eye of each subject received one drop of timolol maleate 0.5% and the fellow eye received a drop of placebo. Measurements of OABPd and OABPs were performed just prior to instillation of the drops, and then 2 hr later. OABPm was calculated as OABPm = OABPd + 1/3 (OABPs - OABPd). No significant changes in OABPd, OABPs or OABPm were observed following the drops in the timolol-treated eyes or in the placebo-treated eyes. A significant difference (P = 0.0198) was found, however, when the changes in OABPm occurring in the timolol-treated eyes were compared with the changes occurring in the placebo-treated eyes, suggesting that the drug may have an effect upon ophthalmic artery pressure and retinal artery pressure that is expressed differently in each eye.

Administration, Topical

Retinal circulation during a spontaneous rise of intraocular pressure.

The retinal haemodynamic changes occurring in an eye with a spontaneous elevation of intraocular pressure were investigated by bidirectional laser Doppler velocimetry and monochromatic fundus photography. At an intraocular pressure of 47 mmHg the blood velocity and volumetric blood flow rate were significantly smaller and arterial blood velocity pulsatility was significantly greater than normal. The corresponding 88% reduction in perfusion pressure was accompanied by a 67% reduction in total retinal blood flow, indicating that autoregulation is not efficient at this level of intraocular pressure. An Octopus visual field examination obtained immediately following blood flow measurements suggested that the central retina can preserve a fairly good function under a total retinal blood flow rate of about one-third of the normal value.

Adult

Effect of an insulin-induced decrease in blood glucose on the human diabetic retinal circulation.

The effect of an insulin-induced decrease in blood glucose on the retinal blood flow (Q) was studied in 12 type II diabetics, using bidirectional laser Doppler velocimetry (BLDV) and monochromatic fundus photography. Q was first measured during hyperglycemia and then during normoglycemia which was achieved within approximately 3 hours by intravenous insulin administration. At normoglycemia, Q was 15% lower than at hyperglycemia (P less than 0.001). The decrease in Q was larger in patients with shorter disease duration. The authors also determined the regulatory change in Q during 100% oxygen breathing. Although this response remained subnormal, it was improved significantly in normoglycemia (P less than 0.01), particularly in those patients whose blood glucose level was decreased at a slower rate, suggesting that a gradual decrease in blood glucose may be beneficial.

Adult

Laser Doppler velocimetry study of retinal circulation in diabetes mellitus.

Bidirectional laser Doppler velocimetry and monochromatic fundus photography were used to investigate retinal circulation in 26 normal subjects and in 51 insulin-treated diabetic patients with no retinopathy, background retinopathy (BDR), proliferative retinopathy (PDR), and patients with PDR who had been treated by panretinal photocoagulation (PDR-PRP). Measurements were obtained from main temporal retinal vessels in each eye. Venous diameter at the site of laser Doppler velocimetry measurements was significantly greater than normal in patients with BDR and PDR. The maximum velocity of red blood cells was significantly lower than normal in eyes with diabetic retinopathy. Calculated volumetric blood flow rate, however, was not significantly different from normal in eyes with no retinopathy, BDR, and PDR, and was significantly decreased from normal in patients with PDR who had been treated by panretinal photocoagulation. A comparison between this technique and the fluorescein dye dilution technique is provided.

Adult

Effect of panretinal photocoagulation on retinal blood flow in proliferative diabetic retinopathy.

The effect of panretinal photocoagulation (PRP) on retinal volumetric blood flow rate and its regulatory response to hyperoxia was investigated in a main temporal vein of 15 eyes with proliferative diabetic retinopathy, using bi-directional laser Doppler velocimetry and monochromatic fundus photography. At an average of 4 +/- 2 months after the beginning of PRP, retinal venous diameter decreased from an average of 174 +/- 20 micron to 162 +/- 19 micron (P less than 0.01), red blood cell velocity decreased from 1.3 +/- 0.4 cm/sec to 1.1 +/- 0.4 cm/sec (P less than 0.01), and blood flow decreased from 11.5 +/- 3.8 microliter/min to 8.4 +/- 3.3 microliter/min (P less than 0.001). The regulatory response to hyperoxia, characterized by the percentage decrease in retinal blood flow during 100% oxygen breathing, improved from 20 +/- 15% prior to treatment to 45 +/- 12% following treatment (P less than 0.001). The decrease in retinal blood flow is most likely due to a decrease in viable retinal tissue and an improvement in retinal oxygenation following PRP. The increase in the regulatory response to 100% O2 breathing following PRP may also result from such an improved retinal oxygenation.

Adult

Autoregulation of human retinal blood flow. An investigation with laser Doppler velocimetry.

The effect of acute changes in mean retinal perfusion pressure, P (2/3 of mean brachial artery blood pressure minus IOP), on retinal volumetric blood flow rate, Q, was investigated in normal volunteers. Changes in Q were determined from Q = k X Vmax X D2, where Vmax is the center line red blood cell velocity measured from temporal veins by laser Doppler velocimetry, D is the vessel diameter obtained by monochromatic fundus photography, and k is a constant of proportionality. A suction cup was used to induce step changes in IOP and, consequently, in P. The magnitude of the steps ranged from 10-32 mmHg. During the first 30 sec after a step decrease in P, Vmax and Q were significantly smaller than at rest by an amount proportional to the decrease in P. Thereafter, Vmax and Q increased markedly towards their values at rest, although P changed comparatively little during this period of time. Time constant of the corresponding decrease in vascular resistance, R(t) = P(t)/Q(t), was approximately 45 sec. There was no significant change in D during elevated IOP. Removal of the cup induced an immediate step increase in P, Vmax, D, Q, and R. Thereafter, Vmax, D, Q, and R returned to their values at rest (time constant of the change in R was about 30 sec), while P remained nearly constant. The rapid change in vascular resistance following a step decrease and increase in P can be attributed to an active process that attempts to maintain blood flow close to normal, in spite of changes in perfusion pressure (autoregulation).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effect of topical timolol on the human retinal circulation.

The effect of topical timolol maleate 0.5% on the retinal circulation was investigated in 14 normal subjects using laser Doppler velocimetry and monochromatic fundus photography. In a double masked, randomized design, one eye received two drops of timolol maleate 0.5% and the fellow eye received two drops of placebo. Vessel diameter, maximum velocity of red blood cells, and volumetric blood flow rate were determined in a major temporal vein of each eye just prior to the instillation of drops, and then 90 min later. In comparison to the baseline value, there was a significantly larger average percentage increase in maximum velocity of red blood cells and volumetric blood flow rate in the timolol-treated eyes (11.0% and 13.2%, respectively) than in the control eyes (2.2% and 1.5%, respectively, paired t-test, P less than 0.05). No significant change in venous diameter was detected. No significant linear correlations were found between the percentage change in maximum velocity of red blood cells and mean brachial artery blood pressure, and between the percentage change in volumetric blood flow rate and mean brachial artery pressure in the placebo-treated eyes, whereas significant correlations were present between these quantities in the timolol-treated eyes (P less than 0.01 and P less than 0.05, respectively). The lack of such correlations in the control eyes is probably due to autoregulation of the retinal circulation. The presence of correlations in the timolol-treated eyes suggests that the drug may affect the capacity of the retina to autoregulate.

Administration, Topical