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B A Berkowitz

Publications and source records attributed to B A Berkowitz.

At least 19 recordsLinked to original sources
PubMed1992

Blood-retinal barrier breakdown caused by diode vs argon laser endophotocoagulation.

We compared the effects of argon and diode laser endophotocoagulation on blood-retinal barrier breakdown using real-time magnetic resonance imaging following intravenous gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) injection. Endophotocoagulation was performed on eyes of pigmented rabbits with either the argon or the diode laser to produce ophthalmoscopically similar lesions. Magnetic resonance imaging studies were performed either 2 or 7 days after laser treatment, and coronal T1-weighted proton images were obtained in the first 20 minutes following Gd-DTPA injection. The mean signal intensity over a region of interest in the vitreous cavity was analyzed, and an initial rate analysis was performed on each time-course curve. Two days after treatment, argon laser-treated eyes showed significantly greater leakage of Gd-DTPA than diode laser-treated eyes. The leakage in both groups was substantially reduced by posttreatment day 7. Histopathologic examination performed 2 days following photocoagulation showed less damage of the retinal pigment epithelium and more severe occlusion of the choriocapillaris and deep choroidal vessels in diode laser-treated eyes. These changes may serve to explain the observed differences in Gd-DTPA leakage.

Animals↗
PubMed1992

Measurement of preretinal oxygen tension in the vitrectomized human eye using fluorine-19 magnetic resonance spectroscopy.

We obtained oxygen measurements from a human eye that contained small preretinal droplets of perfluorotributylamine (FTBA) by using fluorine-19 magnetic resonance spectroscopy. These droplets were the remainder of a larger volume of FTBA that was used as an intraoperative retinal tamponade during retinal detachment repair. The spin-lattice relaxation rate ([T1]-1) of the FTBA fluorine nuclide was obtained that could then be related, by direct proportionality, to droplet PO2. With the patient in a supine position, the droplets could be positioned over the macula in the preretinal vitreous space, whereon the FTBA PO2 could be influenced by the preretinal oxygen concentration. Preretinal PO2 values, derived from magnetic resonance spectroscopy, were in the range of 6 to 9 mm Hg, although multiple components were identified that were suggestive of a heterogeneous distribution of PO2 values in the population of droplets. To our knowledge, this investigation is the first to demonstrate the feasibility of this approach to performing long-term, noninvasive preretinal oxygen measurements in the vitrectomized human eye by using small droplets of a liquid perfluorochemical.

Adult↗
PubMed1992

Treatment with intravitreal steroid reduces blood-retinal barrier breakdown due to retinal photocoagulation.

The effect of corticosteroid treatment on blood-retinal barrier breakdown caused by argon-laser panretinal photocoagulation was evaluated in the rabbit eye. One day before photocoagulation, eyes were given either a sub-Tenon (20-mg) or intravitreal (2-mg) injection of triamcinolone acetonide. The severity of blood-retinal barrier breakdown was measured after photocoagulation using rapid sequential magnetic resonance imaging following intravenous administration of gadolinium diethylenetriaminepentaacetic acid. Leakage of gadolinium diethylenetriaminepentaacetic acid into the vitreous space was significantly lower in eyes that received intravitreal triamcinolone acetonide than in control eyes (P = .007); however, sub-Tenon triamcinolone acetonide produced no significant reduction in leakage (P = .65) compared with controls. Fluorescein angiography supported the magnetic resonance imaging findings. We conclude that retinal photocoagulation in the rabbit eye produces blood-retinal barrier breakdown that is partially amenable to corticosteroid treatment.

Animals↗
PubMed1992

Oxygen kinetics in preretinal perfluorotributylamine.

Previous studies have relied on various electrodes or probes to monitor preretinal oxygen tension in an effort to gain insight into retinal oxygenation. In order to corroborate and extend the results of such studies, we developed a relatively non-invasive method of determining preretinal oxygen tension using 19F nuclear magnetic resonance (NMR) spectroscopy. Small liquid perfluorocarbon (LPFC) droplets were injected into the preretinal vitreous space of the rabbit eye. The T1 value obtained from the fluorine nuclide could then be used to determine preretinal oxygen tension (PO2) with a high degree of sensitivity, since the fluorine spin-lattice relaxation rate (T1)-1 in LPFCs is directly proportional to PO2 under conditions of no flow and known temperature. In the present study, we investigated the oxygen uptake and clearance rates from small preretinal droplets of the LPFC perfluorotributylamine (FTBA) in response to step changes in arterial PO2. At all FTBA volumes examined (2, 10 and 100 microliters), the oxygen uptake and clearance curves were well approximated by a simple exponential equation with mean time constants 9.8/15.3, 21.4/19.4 and 77.7/45.3 min (uptake/clearance), respectively. Following return to normoxemic (baseline) conditions, FTBA droplets provided a preretinal PO2 of 39.4 +/- 9.2 mmHg (mean +/- S.D., n = 12). The 19F NMR method provides a measure of steady-state preretinal PO2 that independently verifies and complements information obtained using oxygen-sensitive microelectrodes or probes. However, the long time constants for oxygen uptake and clearance, particularly in FTBA volumes on the order of 10 microliters and greater, may represent a practical limitation of this method for determining rapid oxygen flux in the preretinal vitreous space.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Accurate and precise measurement of blood-retinal barrier breakdown using dynamic Gd-DTPA MRI.

Dynamic T1-weighted magnetic resonance imaging (MRI) after the injection of Gd-DTPA is a promising method for investigating breakdown of the blood-retinal barrier (BRB). Previously, the authors demonstrated that in a T1-weighted image, the initial rate of change in the vitreous water MRI signal as gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enters the vitreous space strongly correlated with the extent of BRB breakdown. Here, a practical approach to measuring a more relevant physiologic parameter is presented: the permeability surface area product (PS). The theory is a development of earlier work used in investigating the breakdown of the blood-brain barrier. The accuracy and precision of this approach was investigated in rabbits pretreated with sodium iodate (30 mg/kg intravenously). The MRI-derived PS normalized to the area of leaky retina (5.65 +/- 0.25 x 10(-4) cm/min, mean +/- standard error of the mean; n = 6) was compared to a similarly normalized PS calculated using a classical physiologic method (4.12 +/- 0.73 x 10(-4) cm/min; n = 6). Good agreement between the two methods was found (P = 0.09). This result demonstrates that the MRI-derived PS is an accurate and precise measure of BRB breakdown under these conditions. The mathematical model of Gd-DTPA distribution in vivo also is validated. Based on these results, several potential sources of error are discussed, including the effect of back-flow of Gd-DTPA from the vitreous space to the plasma, the underlying vascular patency, and MRI slice selection.

Animals↗
PubMed1992

In vivo imaging of breakdown of the inner and outer blood-retinal barriers.

Real-time contrast-enhanced magnetic resonance imaging (MRI) was used to distinguish between experimentally induced breakdown of the vascular (inner) and retinal pigment epithelial (RPE; outer) blood-retinal barrier (BRB) in vivo. Pigmented rabbits were treated with intravenous sodium iodate 30 mg/kg, (a specific RPE cell poison), intravitreal N-ethylcarboxamidoadenosine (NECA) 10(-3) mol/l (which specifically disrupts the vascular BRB), or retinal diode laser photocoagulation. Coronal T1-weighted proton images were acquired in a timed sequence after intravenous injection of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Images were analyzed to localize leakage of Gd-DTPA and determine the permeability surface area product normalized per unit area (PS). The pattern of enhancement observed in eyes treated with sodium iodate differed clearly from that in eyes treated with NECA. PS' values were significantly higher in eyes treated with sodium iodate than with NECA. Simultaneous leakage from the outer and inner BRB in eyes treated with dense retinal laser photocoagulation could be localized and quantitated independently.

Adenosine↗
PubMed1991

Quantitative determination of the partial oxygen pressure in the vitrectomized rabbit eye in vivo using 19F NMR.

We have quantitatively determined the PO2 within the vitreous space of the vitrectomized rabbit eye in vivo using 19F NMR and perfluorotributylamine (FTBA). The results of the present work are in good agreement with previous measurements of PO2 within the nonvitrectimized rabbit eye obtained using oxygen microelectrodes. In this study, good precision and accuracy were achieved by: (1) having minimal flow effects present, (2) optimizing the signal-to-noise through the use of neat FTBA and surface coil transmission and detection, and (3) performing an inversion-recovery pulse sequence, with adiabatic pulses, to optimize the dynamic range of the T1 experiment. Possible deleterious effects on the measured T1 due to the vitreal temperature gradient are discussed. To the best of our knowledge the results of this study demonstrate, for the first time, a quantitative determination of intraocular PO2 in vivo using 19F NMR and FTBA.

Animals↗
PubMed1991

Blood-retinal barrier breakdown investigated by real-time magnetic resonance imaging after gadolinium-diethylenetriaminepentaacetic acid injection.

Recent magnetic resonance imaging (MRI) studies show that gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) entry into the vitreous space can be used as a qualitative marker of blood-retinal barrier (BRB) disruption. To determine if a more quantitative measurement of BRB breakdown could be obtained, the utility of acquiring real-time, T1-weighted proton images was studied after Gd-DTPA injection. Two days before the MRI experiment, panretinal photocoagulation was done. The mean signal intensity over selected regions-of-interest (ROI) in the vitreous and anterior chamber was followed before and after (0, 10, 20, 30, 45, and 60 min) Gd-DTPA injection (1.0 mmol/kg, intravenously). At every laser power setting used in this study (0, 200, 400, 600, and 800 mW), the change in the mean signal intensity could be approximated by a simple exponential equation. However, the time constants determined for these curves were too imprecise to be useful as correlates between laser power and BRB breakdown. The slope of the line fit to the data in the first 20 min postinjection (ie, an initial-rate analysis) was a more precise correlate between BRB breakdown and laser power. This slope represented the rate of change in mean signal intensity in the ROI as a result of the entry of Gd-DTPA, and it was called the "leakiness" parameter. The leakiness parameter reflected changes in the permeability surface area product of the BRB if the blood flow and the Gd-DTPA arterial concentration immediately after injection were approximately the same between animals.

Animals↗
PubMed1991

Oxygen kinetics in the vitreous substitute perfluorotributylamine: a 19F NMR study in vivo.

Perfluorocarbon (PFC) vitreous substitutes yielded promising results in the surgical management of retinal detachments. This success is due primarily to their physical properties. However, oxygen kinetics in PFC in vivo have not been investigated. The oxygen flux in the vitreous substitute perfluorotributylamine (FTBA) was assessed in the rabbit eye by monitoring the partial oxygen pressure (PO2) in real-time using Fluorine-19 nuclear magnetic resonance spectroscopy (19F NMR) The spin-lattice relaxation rate (T1)-1 of the CF3 resonance of FTBA is a rapid and sensitive index of PO2. T1-derived PO2 from the FTBA-filled rabbit eye was followed at regular time intervals under different oxygenation protocols. In the first series of experiments, FTBA in the vitreous space was oxygenated by ventilating the rabbit with a mixture of 95% O2 and 5% CO2. The oxygen uptake profile could be approximated by a simple exponential function with a time constant of 159 +/- 110 min (mean +/- SD, n = 3). A more reproducible correlate was obtained by performing an initial rate analysis on the first hour of ventilation with high oxygen levels. This analysis showed that the rate of increase in FTBA PO2 was 2.34 +/- 0.67 mm Hg/min (mean +/- SD, r2 = 0.99, n = 7). After the animal was removed from the 95% O2/5% CO2 gas and was ventilated with room air, the oxygen clearance profile could be approximated in all cases by a single exponential with a time constant of 59.8 +/- 9.6 min (mean +/- SD, n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

In vivo metabolism of 3-deoxy-3-fluoro-D-glucose.

Recent studies have demonstrated that 3-deoxy-3-fluoro-D-glucose (3-FG) is metabolized to 3-deoxy-3-fluoro-D-sorbitol (3-FS), via aldose reductase, and 3-deoxy-3-fluoro-D-fructose (3-FF), via the sorbitol dehydrogenase reaction with 3-FS, in rat cerebral tissue (Kwee, I. L., Nakada, T., and Card, P. J. (1987) J. Neurochem. 49, 428-433). However, the biochemistry of 3-FG in other mammalian organs has not been investigated making the application of 3-FG as a metabolic tracer uncertain. To address this issue we investigated 3-FG metabolism and distribution in isolated cell lines and in rabbit tissues in vivo with 19F NMR and gas chromatography-mass spectrometry. In general, the production of 3-FS is well correlated with the known distribution of aldose reductase in all the systems studied. Further metabolism of 3-FS to 3-FF was verified to occur in cerebral tissue. Surprisingly, two new fluorinated compounds were found in the liver and kidney cortex. These compounds are identified as 3-deoxy-3-fluoro-D-gluconic acid, which is produced via glucose dehydrogenase activity on 3-FG, and 3-deoxy-3-fluoro-D-gluconate-6-phosphate. Based on enzyme studies, it is argued that the 3-deoxy-3-fluoro-D-gluconate-6-phosphate is derived directly from 3-deoxy-3-fluoro-D-gluconic acid and not as a product of pentose phosphate activity. Direct oxidation and reduction are the major metabolic routes of 3-FG, not metabolism through glycolysis or the pentose phosphate shunt. Thus, 3-FG metabolism coupled with 19F NMR appears to be very useful for monitoring aldose reductase and glucose dehydrogenase activity in vivo.

Aldehyde Reductase↗
PubMed1990

NMR spectral analysis of kinetic data using natural lineshapes.

An automated rapid data analysis scheme for NMR spectroscopy time course studies is presented. This method uses a high signal-to-noise reference spectrum collected at the beginning of a time course as a lineshape model to analyze subsequent low signal-to-noise data collected with higher time resolution. The method is fast (approximately 1 s to evaluate two peaks in a 2K spectrum) and easily implemented on NMR spectrometer computers. An application of this method to spectroscopic studies on the heart is provided.

Humans↗
PubMed1990

Renal distribution and metabolism of [2H9]choline. A 2H NMR and MRI study.

Trimethylamines are required as substrates in the biosynthesis of a number of important molecules in the cell. Herein, we describe the use of choline, deuterated in its 9 methyl positions, as an NMR label for following the distribution and metabolism of methyl groups after intravenous choline infusion. Deuterium (2H) NMR spectroscopy of the rabbit kidney in vivo revealed a linear uptake of infused choline that was directly proportional to the rate of infusion. The sensitivity limit for the spectroscopic studies in vivo was in the order of 100 microM for a 2 min data collection. After the infusion, 2H NMR imaging of the kidney in vivo demonstrated high trimethylamine concentrations in both the cortex and inner medulla but not in the outer medulla. The inner medullary fraction, however, was more labile to diuresis induced by furosemide. Companion high resolution 2H NMR studies of extracts revealed a cortex betaine/choline concentration ratio of 0.69 +/- 0.05 (mean +/- SEM, n = 3) before furosemide administration. Following furosemide infusion, the cortex betaine/choline concentration ratio was 3 +/- 1 (n = 6). Thus, 2H renal images following furosemide treatment can be interpreted as metabolic maps of betaine distribution. In addition, extraction studies revealed high concentrations of labelled choline and betaine in the liver. These data demonstrate that 2H-labelled choline is an effective marker of choline methyl metabolism in vivo and should provide a unique tool for the investigation of this important substrate.

Animals↗
PubMed1990

Sodium-23 nuclear magnetic resonance imaging of the rabbit kidney in vivo.

The mechanism by which the mammalian kidney generates a concentration gradient of sodium from cortex to papilla is still not entirely understood. Studies of how the kidney as an organ generates this gradient have been hampered by the lack of a noninvasive method for monitoring the intrarenal sodium distribution. Herein, we demonstrate the value of sodium-23 nuclear magnetic resonance (23Na-NMR) imaging to nondestructively assess the intrarenal sodium distribution. 23Na-NMR images were obtained from a surgically exposed kidney preparation that showed the two-dimensional distribution of sodium in the rabbit kidney. In the antidiuretic kidney this gradient resulted in papillary sodium concentrations that were approximately threefold higher than cortical values. Serial 23Na-NMR images obtained during saline infusion demonstrated the kinetics by which the sodium gradient increases with diuresis. The half-time for 23Na washout of the medulla of the kidney was approximately 6 min with this protocol. In addition, a three-dimensional data set of the sodium distribution of the kidney was obtained with voxel dimensions of 1.5 mm3 by use of a three-dimensional 23Na-NMR imaging technique. Without surgical exposure, 23Na-NMR images of the rabbit kidney were collected under completely noninvasive conditions by use of a surface coil. The 23Na-NMR signal from the kidney was easily detected; however, to obtain images of comparable signal-to-noise ratio to the surgically exposed kidney, spatial and temporal resolution were significantly reduced.

Animals↗
PubMed1989

Endothelial thromboxane receptors: biochemical characterization and functional implications.

We have identified thromboxane specific receptors in membrane preparations of bovine pulmonary artery endothelial cells using a potent thromboxane specific antagonist, [125I]-PTA-OH in a binding assay. The binding was specific and saturable. Neither thromboxane B2, prostaglandin D2 nor prostaglandin F2 alpha displaced the ligand (0.1 nM) at concentrations up to 10 microM. However, binding was displaced by IPTA-OH greater than SQ29548 greater than U46619. In addition, we observed that thromboxane mimetic U46619 significantly lowered the basal production of prostacyclin and also markedly suppressed bradykinin-stimulated prostacyclin released by endothelial cells. We propose that an important biological effect of thromboxane on vascular endothelial cells may be the suppression of prostacyclin production.

Animals↗