PubMed HealthSearch

Biomedical subjects

G E Sanborn

Publications and source records attributed to G E Sanborn.

At least 19 recordsLinked to original sources

Sustained-release ganciclovir therapy for treatment of cytomegalovirus retinitis. Use of an intravitreal device.

A surgically implantable device for sustained intravitreal release of ganciclovir has been developed. The device delivers ganciclovir intraocularly over approximately 4 to 5 months. Eight patients with acquired immunodeficiency syndrome (AIDS) and associated cytomegalovirus (CMV) retinitis were recruited as part of a phase 1 study. Thirteen eyes with active CMV retinitis underwent surgical implantation of the ganciclovir device. All eyes showed resolution of the CMV retinitis; none showed progression. Visual acuity remained unchanged in three eyes, improved in six eyes, and decreased in four eyes. Surgical complications included mild vitreous hemorrhage, astigmatism, and suprachoroidal placement of the device. Retinal detachment occurred in three eyes as the retinitis resolved. This new intraocular drug delivery system offers many advantages compared with intravenous therapy or repeated intravitreal ganciclovir injections for the management of CMV retinitis in patients with AIDS.

Acquired Immunodeficiency Syndrome

Efficacy of dacarbazine (DTIC) in preventing metastases arising from intraocular melanomas in mice.

At present there are no chemotherapeutic agents that have been proven to be effective in either preventing or retarding the progression of metastases arising from uveal melanomas in human subjects. Dacarbazine (DTIC), the single most effective chemotherapeutic agent in the treatment of cutaneous melanoma, is a potentially useful therapeutic modality for use as an antimetastatic agent in uveal melanoma. However, DTIC has not been evaluated for its ability to impede metastases originating from intraocular melanomas. The present study assessed the antimetastatic efficacy of DTIC in a murine intraocular melanoma model. The results indicate that treatment with DTIC resulted in sharp reductions in the number of spontaneous metastases and a significant prolongation of survival time. Dose-response studies indicated that exceedingly high doses of DTIC were necessary to produce antimetastatic effects even when drug treatment was combined with the calcium channel blocker verapamil. Collectively, the results indicate that DTIC can be an effective adjunctive therapeutic agent when administered at the time of enucleation of the melanoma-containing eye but is ineffectual if administered subsequent to surgery.

Animals

Intravitreal ganciclovir pharmacokinetics in rabbits and man.

Cytomegalovirus (CMV) retinitis occurs in immunocompromised patients and can be treated by repeated intravenous or intravitreal injections of ganciclovir (GCV) or foscarnet. Due to toxicity and complications these modalities are not ideal. The development of alternative administration routes is hindered by a lack of pharmacokinetic data. Devices giving pseudo zero order release of GCV were implanted intravitreally first in rabbits and then in patients with AIDS associated CMV retinitis as part of a Phase I clinical trial. Steady state intravitreal GCV levels were obtained immediately after death and the elimination rate constants were calculated assuming first order pharmacokinetics. Normalizing for retinal surface area, distribution volume and anatomic volume, the retinal elimination rate constants were calculated. These were found to be 0.017 cm-2hr-1 in rabbits and 0.015 cm-2hr-1 in man. This indicates that the rabbit eye is a good model for studying intravitreal pharmacokinetics of ganciclovir and suggests a common elimination mechanism which may be trans-retinal.

Animals

Mouse model of brachytherapy in consort with enucleation for treatment of malignant intraocular melanoma.

The efficacy of brachytherapy in the treatment and prevention of metastasis of intraocular melanoma was investigated in a mouse model. A highly metastatic subline of B16 melanoma was transplanted into the anterior segment of C57BL/6 mice and allowed to grow. Brachytherapy was delivered by means of miniature iodine 125 seeds implanted in shallow subcutaneous pockets of the upper eyelid margin of these mice, and 25 Gy of radiation was delivered between days 12 and 14. This brachytherapy reduced both the tumor volume and the number of mitotic figures per high-power field compared with irradiated controls. In a second experiment, 25 Gy of brachytherapy was delivered before enucleation, straddling enucleation, and after enucleation; there was a significant reduction in metastasis when radiation was delivered prior to enucleation. This model may be useful in conducting further studies involving brachytherapy with 125I plaque implants.

Animals

The suicide of General Emory Upton: a case report.

On the evening of March 14, 1881, Emory Upton inexplicably and unexpectedly committed suicide. He was acknowledged as the United States Army's leading tactician of his day; his drill manual, A New System of Infantry Tactics, Double and Single Rank, had been officially adopted by the Army in 1867. The entire Army was stunned by the news. For the past century, a mystery has remained as to the medical factors that led to his suicide. This paper will examine the existing medical records and offer a probable modern diagnosis for this unique 109-year-old case report.

Adult

Contrast sensitivity versus static visual field testing during experimental elevation of intraocular pressure.

Contrast sensitivity testing has been recommended as a more sensitive indicator of early visual loss than visual field testing. Using gravity inversion to induce an intraocular pressure rise, we performed contrast sensitivity testing on each eye of 10 normal subjects in the upright and inverted positions. Contrast sensitivity results were not altered in the head-down position, even though in 5 of the 10 subjects (7 of 20 eyes), visual field alterations on static perimetry were elicited during inversion. In both of these evaluations, the subject's results in the upright position served as the control, freeing us from reliance upon age-matched populations. We conclude that precise measurement of static thresholds with automated perimetry is more sensitive than routine contrast sensitivity testing in detecting visual dysfunction related to transient acute elevations of intraocular pressure.

Adult

Progressive capillary nonperfusion in temporal branch retinal vein obstruction.

We studied 31 eyes with nonischemic temporal branch retinal vein obstruction (TBRVO) of six months' duration or less. Each eye had an initial and at least one follow-up fluorescein angiogram according to the clinical course. Five eyes had sufficient additional capillary nonperfusion by angiography to warrant reclassification into the ischemic category. This conversion to an ischemic TBRVO pattern was documented as early as one month and as late as 14 months (average 5.2 months) after initial evaluation. Males dominated the progressive group (P less than 0.005); age, sex, initial visual acuity, and associated medical and ocular conditions were not significantly different between progressive and nonprogressive eyes (P greater than 0.05). A nonischemic TBRVO may convert to an ischemic pattern, placing these eyes at increased risk for the subsequent development of neovascular complications.

Aged

Clinical evaluation of the Cavitron Biotronics tonometer.

The Mackay-Marg tonometer has been shown to be an accurate tonometer for the measurement of intraocular pressure in eyes with both normal and diseased corneas. This tonometer is no longer manufactured and has been replaced by the Cavitron Biotronics tonometer that works on the same principle but utilizes a different recording display. The Cavitron Biotronics tonometer's accuracy was compared with that of the Goldmann applanation tonometer in 75 eyes. The Cavitron Biotronics tonometer is not as accurate as the original Mackay-Marg tonometer for individual readings. However, if four readings are taken, the value of the Cavitron Biotronics tonometer that correlated best with Goldmann applanation tonometry was the one reading of the four with the highest value. Using this one value, the Cavitron Biotronics instrument underestimates the true intraocular pressure below 27 mm Hg and overestimates it above this value.

Clinical Trials as Topic

Optic nerve dysfunction during gravity inversion. Visual field abnormalities.

Inversion in a head-down position (gravity inversion) results in an intraocular pressure of 35 to 40 mm Hg in normal subjects. We used computerized static perimetry to measure the visual fields of normal subjects during gravity inversion. There were no visual field changes in the central 6 degrees of the visual field compared with the baseline (preinversion) values. However, when the central 30 degrees of the visual field was tested, reversible visual field defects were found in 11 of 19 eyes. We believe that the substantial elevation of intraocular pressure during gravity inversion may pose potential risks to the eyes, and we recommend that inversion for extended periods of time be avoided.

Adult

Reduction of enucleation-induced metastasis in intraocular melanoma by periorbital irradiation.

The optimum treatment of malignant choroidal melanoma remains controversial. Some authors have hypothesized that enucleation promotes metastatic disease. This hypothesis has been demonstrated in the B16F10 melanoma mouse model. The present study used this model to examine the effect of external beam irradiation as a means of reducing metastases induced by enucleation. The results show a dose-dependent reduction in the DNA synthesis of irradiated melanoma cells. Administration of 800 cGy (800 rad) of radiation produced a 90% reduction in DNA synthesis; however, higher levels of radiation failed to produce further depression of cell proliferation. Irradiation of melanoma cells before intravenous injection resulted in a significant dose-dependent reduction in the number of lung metastases. While there was no effect with 100 cGy (100 rad) of radiation, 1000 cGy (1000 rad) produced a 95% reduction in metastases. In the animal model of enucleation-induced metastasis, 2000 cGy (2000 rad) delivered to the orbit either before or after enucleation produced a significant reduction in the number of lung tumors, compared with animals that did not undergo irradiation; 1000 cGy (1000 rad) delivered before enucleation did not have such an effect. These studies provide evidence that periorbital external beam irradiation is useful in reducing metastases following enucleation of a malignant melanoma in this animal model.

Animals

The afferent pupillary defect in asymmetric glaucoma.

The OCTOPUS 2000 perimeter and a central 30 degrees program were used to study consecutively 27 patients with glaucoma who had either a relative afferent pupillary defect (APD) or asymmetric optic nerve cupping without an APD. The mean difference in visual field sensitivity between fellow eyes was 48.2% (range, 13% to 93%) for the APD group and 5.5% (range, 0% to 9.0%) for the non-APD group. The mean difference in cup-disc ratio was 0.43 (range, 0.2 to 0.6) for the APD group and 0.24 (range, 0.2 to 0.3) for the non-APD group. The APD depth was quantitated with neutral density filters and correlated with visual field asymmetry but not with cup-disc ratio asymmetry. There was no overlap between the APD and non-APD groups in the amount of visual field asymmetry: Every patient with a sensitivity difference of 13% or greater had an APD. The presence of an APD indicates that a threshold of asymmetric optic nerve damage has been exceeded. With automated perimetry, this threshold can be quantitated and may improve the assessment of patients with glaucoma.

Afferent Pathways

Further linkage data on Norrie disease.

We obtained a LOD score of +1.61 using DNA marker L1.28 in 5 generations of a family with Norrie disease, raising the total LOD score to +5.42. There have been no recombinations between the 2 loci in any family to date, making the marker useful for genetic counseling.

Blindness

Suicide enzyme inhibition as a chemotherapeutic strategy for controlling metastases derived from intraocular melanomas.

The anti-metastatic effect of two chemotherapeutic agents was analyzed in a murine melanoma model. Difluoromethylornithine (DFMO), a specific irreversible inhibitor of ornithine decarboxylase, was administered as a 2% aqueous solution in the drinking water. A second drug, dacarbazine (DTIC) was administered intravenously in single bolus injections. Each drug produced significant anti-metastatic effects that were manifested by a reduction in the number of pulmonary metastases and in the prolongation of host survival times. Maximal chemotherapy was achieved when both drugs were combined. The specificity, low toxicity, ease of administration, infrequent side effects, and therapeutic effectiveness of DFMO make it an attractive candidate for clinical use in human subjects being treated for uveal melanoma. The effectiveness of DTIC against blood-borne melanoma cells suggests that this drug may prove useful as a prophylactic adjunct in patients undergoing enucleation of a melanoma-containing eye.

Animals

The idling retina: reversible visual loss in central retinal artery obstruction.

Based on experimental studies, sustained total central retinal artery obstruction (CRAO) lasting more than one and one-half hours has been considered to cause irreversible retinal damage. We have seen five cases of patients with pure CRAO that lasted longer than one and one-half hours who regained significant visual acuity. Three of the patients had a completely spontaneous improvement in visual acuity to 20/50 or better. In addition, the other two patients regained significant vision to 20/80 or better with a modified treatment regimen of acetazolamide, inhalation of 5% CO2 and 95% O2, and aspirin. No foveola-sparing cilioretinal arteries were present in any of the cases. We introduce the concept of reversible retinal ischemia following unsustained CRAO to account for these unexpected improvements in visual acuity.

Acetazolamide

Fundus-iris fluorescein angiography: evaluation of its use in the diagnosis of rubeosis iridis.

Fundus-iris fluorescein angiography is a technique that allows iris angiography and retinal angiography to be performed simultaneously, using a single injection of dye and a standard retinal fundus camera. We analyzed the ability of this technique to detect rubeosis iridis. In a study of 200 randomly selected angiograms on 400 eyes, the technique was able to detect 97.2% of all eyes with rubeosis iridis (sensitivity), with a false-positive rate of 1%. In 26 eyes (36.6% of all eyes with rubeosis), it was able to detect rubeosis prior to the development of vessels visible by slit-lamp biomicroscopy. The test was able to correctly identify 98.8% of the eyes without rubeosis (specificity), with a false-negative rate of 0.5%. This technique can be performed routinely as part of retinal angiography.

Aged

Temporal branch retinal vein obstruction: a review.

Two hundred forty-six eyes with temporal branch retinal vein obstruction (TBRVO) were studied prospectively. Of the 85 eyes not receiving laser treatment, 35 (41%) presented with greater than or equal to 20/50 vision and 89% remained in this group; whereas, 29 eyes (34%) presented with less than or equal to 20/200 vision and only 17% improved. Of the 161 eyes receiving laser, 40 (25%) had greater than or equal to 20/50 vision pre-treatment and 75% remained in this group; whereas, 64 eyes (40%) had less than or equal to 20/200 vision pre-treatment and 50% improved. The average final VA (20/70 vs 20/100), risk of developing neovascularization in ischemic TBRVO (3% vs 34%) and risk of vitreous hemorrhage in proliferative TBRVO (10% vs 57%) were all significantly better in treated eyes (p less than or equal to 0.01).

Aged