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Biomedical subjects

W H Stern

Publications and source records attributed to W H Stern.

At least 37 records · Page 2Linked to original sources
PubMed1986

Liposome-mediated delivery of pteridine antifolates to cells in vitro: potency of methotrexate, and its alpha and gamma substituents.

We have examined the growth-inhibitory potency of several pteridines encapsulated in negatively charged liposomes, including methotrexate, methotrexate-gamma-methylamide, methotrexate-gamma-dimethylamide, methotrexate-alpha-aspartate, and a lipophilic methotrexate-phosphatidylethanolamine conjugate. The potency of encapsulated methotrexate is greater than the potency of the free drug for CV1-P cells, but not for other cell lines. The potency of methotrexate-gamma-methylamide and methotrexate-gamma-dimethylamide is only minimally improved by encapsulation. The potency of methotrexate-alpha-aspartate is increased by encapsulation. In addition, the lipophilic methotrexate derivative has demonstrable potency when incorporated in liposomes. We have also examined the potency of several pteridines under conditions where the cells are exposed to the drug for periods shorter than the entire growth assay. Reduction of the exposure time decreases the potency of both encapsulated and free drugs. However, the difference in potency between the encapsulated and free drug is increased, because the potency of the encapsulated drug is affected less. Consequently, encapsulated methotrexate-gamma-aspartate is 300-fold more potent than free drug, if CV1-P cells are exposed to drug for 4 h. Moreover, encapsulated methotrexate is more potent than free methotrexate for growth inhibition of L929 fibroblasts, if the term of exposure is less than 8 h. Potency is least affected by reduction of exposure length for the lipophilic methotrexate derivative.

Cell Line↗
PubMed1986

Extended retinal tamponade in the treatment of retinal detachment with proliferative vitreoretinopathy.

We have used intraocular sulphur hexafluoride or liquid silicone as an adjunct to vitreous surgery in the treatment of a non-randomised sequential series of 19 eyes with retinal detachment complicated by proliferative vitreoretinopathy. We have studied the surgical results and complications of these two tamponades and drawn preliminary conclusions on their use in retinal reattachment surgery. After a seven-month minimum follow-up 13 (68%) of the eyes have reattached retinas. Six (60%) of 10 eyes treated only with silicone have reattached retinas, and four (67%) of six eyes treated only with sulphur hexafluoride gas tamponade have reattached retinas. An additional three eyes treated initially with silicone oil subsequently developed retinal detachments; all were successfully reattached with sulphur hexafluoride tamponade after silicone oil removal. Intraoperative pneumatic retinal reattachment to assess relief of retinal traction combined with the production of widespread chorioretinal adhesions to wall off persistent anterior traction and detachment, as well as extended postoperative gas tamponade of the retina, appears to enhance the surgical results in retinal detachment complicated by proliferative vitreoretinopathy. Silicone oil tamponade of the retina appears to be useful in cases where retinal traction cannot be entirely relieved and in patients who are unable to tolerate the head positioning required for effective gas tamponade of the retina. A controlled clinical study recently begun will be required to define further the precise role of these methods of retinal tamponade.

Adult↗
PubMed1986

Fluoropyrimidine treatment of ocular cicatricial disease.

The authors have studied the antiproliferative and anticontractile effects of fluorouracil, fluorouridine, and fluorodeoxyuridine on rabbit dermal fibroblasts. All three drugs have antiproliferative effects, the order of their efficacy being fluorodeoxyuridine greater than fluorouridine greater than fluorouracil. In contrast, only fluorouridine and fluorouracil have anticontractile effects. Fluorouridine requires less time of exposure and has greater anticontractile effects than fluorouracil. Thymidine eliminates the antiproliferative effects of fluorodeoxyuridine, but has no effect on either the antiproliferative or anticontractile effects of fluorouracil and fluorouridine. These results suggest that the anticontractile effects of the fluoropyrimidines are caused by their incorporation into RNA and not by the inhibition of DNA synthesis. Metabolites of fluorouracil may provide enhanced control of cell proliferation and contractility in the management of ocular disorders such as proliferative vitreoretinopathy and glaucoma.

Animals↗
PubMed1986

Morphological recovery in the reattached retina.

After experimental retinal detachment in the cat, a number of morphological changes take place in retinal and RPE cells. Following reattachment, the ultrastructural relationship between the photoreceptors and the RPE is re-established, but it does not return to the predetachment state even after short detachment episodes coupled with prolonged recovery periods. All of the reattached retinae show some degree of abnormality, ranging from subtle changes in photoreceptor ultrastructure to dramatic degenerative effects in the outer retina. Abrupt transitions in morphology from one reattached area to an adjacent area are not unusual. Photoreceptor recovery varies widely between animals, and between adjacent regions within the same retina. Ensheathment of outer segments by RPE apical processes is abnormal. In some reattached areas rod outer segment dimensions and disc structure are near normal as is the displacement rate of rod outer segment discs. In others, especially in areas of RPE or Müller cell proliferation and hypertrophy, the outer segments are shortened or absent completely, and there is a reduction of cell bodies in the outer nuclear layer. In some retinae, recovery in cones is inferior to that in rods. At short detachment durations (less than 1 wk) morphological recovery in the reattached retina is optimal while at long intervals (greater than 1 month) recovery is poor. The changes at the photoreceptor-RPE interface identified in the reattached cat retina probably have adverse effects on visual recovery when they occur within the human macula.

Animals↗
PubMed1985

5-Fluoroorotate: a new liposome-dependent cytotoxic agent.

The potency of 5-fluoroorotate for inhibition of L929 or CV1-P cell growth is increased by encapsulation in negatively charged liposomes. The optimal liposome composition is dipalmitoylphosphatidylglycerol: cholesterol, 67:33. Unextruded large unilamellar liposomes are the optimal size for delivery. This compound is the second transport-negative drug which we have found to exhibit liposome-dependent delivery.

Animals↗
PubMed1985

Epidemic postsurgical Candida parapsilosis endophthalmitis. Clinical findings and management of 15 consecutive cases.

Fifteen cases of postoperative Candida parapsilosis endophthalmitis occurring secondary to a contaminated lot of an irrigating solution were studied. All patients underwent a vitreous tap or diagnostic and therapeutic vitrectomy. Eleven of the 15 specimens were positive for the organism. Fourteen patients were treated with pars plana vitrectomy surgery. All patients were treated with intravitreal amphotericin B and systemic amphotericin B and 5-fluorocytosine. Two clinical recurrences were successfully treated with intravitreal amphotericin B, removal of the pseudophakos, and oral ketoconazole. The intraocular lens was retained in 11 of the 14 pseudophakic patients. Final visual acuities ranged from 20/25 to no light perception with eight of 15 patients having 20/60 or better visual acuities. Measurable levels of intraocular amphotericin B were found after systemic amphotericin B administration. Two patients with totals of 20 and 30 micrograms of intravitreal amphotericin B over 48 and 96 hours, respectively, had near normal ERGs one year later. Posterior capsulotomy and vitrectomy appear to decrease amphotericin B toxicity and allow sequential intraocular injection of this drug within a short time period.

Aged↗
PubMed1985

Intraocular penetration of systemically administered antifungal agents.

Amphotericin B, 5-flucytosine (5-FC), and ketoconazole levels were estimated in vitreous and aqueous samples taken from four patients undergoing therapeutic vitrectomy for fungal endophthalmitis. The levels of amphotericin B in the vitreous of three patients were low (.04 - .17 microgram/ml). However, 5-FC was present in a concentration of 22.2 micrograms/ml in one patient. In another case the aqueous level of ketoconazole was 0.35 microgram/ml. The vitreous in the same patient contained 0.71 microgram/ml of the drug.

Amphotericin B↗
PubMed1983

Fluorouracil therapy for proliferative vitreoretinopathy after vitrectomy.

Fluorouracil effectively inhibits epiretinal membrane formation and traction retinal detachment after vitrectomy surgery. When 0.5 mg of fluorouracil was administered intraocularly every 24 hours for seven days, traction retinal detachment two weeks after the intraocular injection of 200,000 cultured retinal pigment epithelial cells occurred in 12 of 12 control eyes but in only six of 14 eyes treated with fluorouracil (P less than .001). Four weeks after cell injection, eight of 12 eyes treated with fluorouracil had traction retinal detachments whereas 12 of 12 control eyes did (P less than .001). The height of the traction retinal detachment four weeks after intraocular injection of 200,000 cultured retinal pigment epithelial cells was reduced 50% in eyes treated with 0.5 mg of fluorouracil every 24 hours for seven days compared to control eyes (P less than .001). When the number of injected retinal pigment epithelial cells was increased to 400,000 cells and 1.25 mg of fluorouracil was administered intraocularly every 24 hours for seven days, traction retinal detachment two weeks after injection occurred in 15 of 15 eyes in the control group but in none of ten eyes in the treated group. Four weeks after cell injection, eight of eight eyes in the control group and five of five eyes in the fluorouracil-treated group had detachments and the mean height of the detachments in the two groups was equal. Autoradiography of the epiretinal membranes in eyes injected with 200,000 cultured retinal pigment epithelial cells and labeled for two hours with tritiated thymidine showed that 0.8% of the epiretinal cell nuclei were labeled two weeks after cell injection but that no labeled cells were present in the fluorouracil-treated eyes. Tritiated thymidine labeling of epiretinal cells in the fluorouracil-treated eyes was first noted three weeks after the cell injection. The presence of tritiated thymidine labeling in the fluorouracil-treated eyes correlated with an increase in the number of epiretinal cells and an increase in the incidence of traction retinal detachment.

Animals↗
PubMed1983

Ocular toxicity of fluorouracil after vitrectomy.

The retinal and corneal toxicity of fluorouracil in the rabbit eye after lensectomy and vitrectomy depended on both the dosage and the frequency of intraocular injection and was reversible at certain dosages. All eyes in Group 1 (1.25 mg of fluorouracil every 12 hours for four days and then every 24 hours for three days) had opaque corneas by three days; these did not clear for four weeks. Histologic studies showed loss of photoreceptor outer segments and loss of ribosomes in all the retinal cells examined. The electroretinographic b-wave decreased to 0% of the baseline value (no b-wave), and did not recover after three weeks. In Group 2 eyes (1.25 mg of fluorouracil every 24 hours for seven days), corneal opacification increased to a maximum after two weeks and gradually decreased by four weeks. The electroretinographic b-wave diminished to 9.6% of the baseline value at two weeks but later recovered to 62.5% of the baseline value at three weeks. Histologic studies showed loss of photoreceptor outer segments and ribosomes at nine days; both returned to near normal after five weeks. Clinical, electrophysiologic, and histologic studies showed no toxicity in Group 3 eyes (0.5 mg of fluorouracil every 24 hours for seven days). This dosage of fluorouracil exerts a significant antiproliferative effect on injected retinal pigment epithelial cells and is well tolerated by the rabbit eye.

Animals↗
PubMed1983

Metastatic adenocarcinoma presenting as bilateral blindness.

A 71-year-old man had bilateral shallow retinal detachments. An extensive medical work-up was unrevealing. A "skinny-needle" biopsy of retrocrural lymph nodes under computed tomographic control supported a diagnosis of metastatic adenocarcinoma to his choroid. A review of the literature on metastatic ocular cancer is presented.

Adenocarcinoma↗
PubMed1983

Retinal detachment in the cat: the pigment epithelial-photoreceptor interface.

Twenty-six cat retinae were surgically detached by injecting fluid into the subretinal space (SRS). The retinae were then studied by light and electron microscopy at detachment intervals ranging from 1/2 hr to 14 months. Degenerative and proliferative changes occur at the retinal pigment epithelial (RPE)-photoreceptor interface very soon after detachment, and the severity of these changes depends upon both the duration and height of the detachment. The specialized apical RPE processes that ensheath the outer segments are replaced by a uniform fringe of short, undifferentiated processes. The apical RPE surface becomes mounded, and this mounding becomes more pronounced at longer detachment durations. Labeling experiments with 3H-thymidine showed that some cat RPE cells enter a phase of stimulated DNA synthesis 12-24 hrs after detachment; RPE mitotic figures are first apparent 48 hrs after detachment. In the cat, discrete regions of proliferated RPE cells usually appear in one of several configurations. A number of different cell types, including polymorphonuclear neutrophils, monocytes at various maturational stages, photoreceptor cells, Müller cells, and RPE cells, appear in the expanded SRS of detached retinae. Rod and cone outer segments degenerate rapidly and become membrane bound sacs by 3 days postdetachment; the assembly of new outer segment membrane apparently does not stop completely even at moderately long detachment intervals (ie, 2 months). Degenerative changes in the inner segments do not take place with the same rapidity as those in the outer segments. The changes that occur at the RPE-photoreceptor interface are rapid, progressive, and sometimes irreversible events that have significant implications for photoreceptor recovery following retinal reattachment surgery.

Animals↗
PubMed1983

Retinal detachment in the cat: the outer nuclear and outer plexiform layers.

The retinae of cats were surgically detached for 1/2 hr to 14 months, and the outer nuclear (ONL) and outer plexiform layers (OPL) were studied by light and electron microscopy. The longer the duration or the greater the height of detachment the more likely was the occurrence of cell death. Histologic signs of degeneration were present 1 hr after detachment. The number of photoreceptor nuclei in the ONL decreased significantly by 1 month. Loss of cells in the ONL occurred by necrosis and by the migration of photoreceptor cell bodies into the subretinal space. The OPL degenerated by the necrosis of cell processes and synaptic terminals and by the retraction of the synaptic terminals. By 2 weeks most synaptic terminals were necrotic or in the process of retracting. Photoreceptor synaptic contact with second order neurons was diminished by 30 days and was essentially absent by 50 days. Müller cells proliferated and hypertrophied; their nuclei and cell processes filled the intraretinal spaces left by the degenerating photoreceptors. In addition, Müller cells protruded into the subretinal space and formed multiple layers of cell bodies and processes between the retina and retinal pigment epithelium. By 14 months these subretinal Müller cell processes covered the entire detached retina, and appeared morphologically like an astroglial scar. Similar changes in human retinal detachments may significantly influence the degree of visual recovery after retinal reattachment, especially in retinae detached for more than a few days.

Animals↗
PubMed1982

Epiretinal membrane formation after vitrectomy.

Our experimental model of epiretinal membrane formation in the rabbit eye after lensectomy and vitrectomy provides a way of studying pharmacologic and surgical approaches to inhibiting epiretinal cellular proliferation and contraction in the eye that has undergone vitrectomy. We injected 400,000 tissue-cultured retinal pigment epithelial cells onto the retinal surface of rabbit eyes that had undergone lensectomy, vitrectomy, and fluid-gas exchange. By one week, a funnel-shaped detachment of the medullary rays had occurred in 100% of the injected eyes. Histologically, the cells formed an epiretinal membrane by six hours after injection and caused major wrinkling of the inner retina after 24 to 48 hours. The percentage of tritiated-thymidine-labeled epiretinal cells increased dramatically 24 hours after injection and then declined. Cellular membranes bridging the optic nerve, followed by growth and contraction of the epiretinal cells on the detached internal limiting membrane, were responsible for the closed funnel appearance of the medullary rays.

Animals↗