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Biomedical subjects

P Sternberg

Publications and source records attributed to P Sternberg.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cat scratch disease: posterior segment manifestations.

OBJECTIVE: To evaluate the posterior segment findings seen in ocular cat scratch disease. DESIGN: Retrospective case series. PARTICIPANTS: There were 24 patients (35 eyes) with choroidal, retinal, or optic disc manifestations of Bartonella infection evaluated at the authors' institutions over a 6-year period. MAIN OUTCOME MEASURES: Clinical and photographic records were reviewed for evidence of disc edema, macular star, foci of retinitis or choroiditis, choroidal masses, optic nerve masses, vascular-occlusive events, or other findings. RESULTS: Discrete white retinal or choroidal lesions, 50 to 3000 microm in diameter, were the most common posterior segment findings in this series of patients (83% of eyes, 83% of patients). Optic disc swelling was the second most common finding (46% of eyes, 63% of patients) followed by a macular star (43% of eyes, 63% of patients). Vascular-occlusive events were also seen (14% of eyes, 21% of patients), and the site of occlusion was found to be intimately associated with the aforementioned retinal lesions. Final visual acuity was 20/25 or better in 26 (74%) of 35 eyes and was similar in both treated and untreated patients. CONCLUSION: Isolated foci of retinitis or choroiditis were the most common ocular manifestation of cat scratch disease in the authors' patient population, but an array of posterior segment findings may occur.

Adolescent↗
PubMed1999

Retinal phototoxicity.

Phototoxic retinal lesions are a product of advances in operative technology. Use of more powerful light sources in both anterior and posterior segment cases and an increase in surgical complexity requiring longer operative times (especially during ophthalmic training) have rendered photic injury a real danger for all surgeons. Though we enjoy the enhanced view offered by modern light sources, we must also keep in mind the additive, detrimental effect of prolonged light exposure. With increased awareness of this potential hazard, surgeons can take steps to minimize the chance of generating a sight-threatening phototoxic lesion.

Animals↗
PubMed1999

Oxidant-induced apoptosis in cultured human retinal pigment epithelial cells.

PURPOSE: To determine the mechanism of oxidant-induced cell death in cultured human retinal pigment epithelium (hRPE). METHODS: Cultured hRPE cells were treated with different concentrations of a chemical oxidant, t-butylhydroperoxide (tBH), for different periods of time. Apoptosis was determined with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) and flow cytometry. Mitochondrial membrane potential (mtdelta psi) was measured by rhodamine 123 staining and subsequent flow cytometry. Release of mitochondrial cytochrome c (cyt c) and cleavage of procaspase 3 and caspase substrates were determined by western blot analysis. RESULTS: t-Butylhydroperoxide caused time- and dose-dependent activation of apoptosis in hRPE, indicated by characteristic morphologic changes; TUNEL-positive labeling; phosphatidylserine (PS) exposure; and procaspase 3, poly(ADP-ribose)polymerase, lamin, and tubulin cleavage. An early decrease of mtdelta psi was observed before caspase activation, together with the release of mitochondrial cyt c. CONCLUSIONS: Results indicate that tBH can induce apoptosis in hRPE, probably by triggering the mitochondrial permeability transition, which results in swelling and release of mitochondrial intermembrane proteins.

Aged↗
PubMed1999

Effect of dietary inducer dimethylfumarate on glutathione in cultured human retinal pigment epithelial cells.

PURPOSE: To determine the effect of dimethylfumarate (DMF), an inducer of glutathione (GSH)-dependent detoxification, on intracellular GSH levels in cultured human retinal pigment epithelium (hRPE) cells, its mechanism of action, and its effect on hRPE cells subjected to oxidative injury. METHODS: Established hRPE cell lines were treated with DMF and assayed by high-pressure liquid chromatography for intracellular and extracellular GSH levels. Quantification of gamma-glutamylcysteine synthetase (GLCL) was determined through northern and western blot analyses, and activity was measured. Effects of pretreatment with DMF on GSH redox status of hRPE cells was determined. Sensitivity of hRPE cells to oxidative stress was determined using tert-butylhydroperoxide as the oxidative agent. RESULTS: Dimethylfumarate caused a transient decrease followed by a significant increase in intracellular GSH. Glutathione increased maximally at 24 hours with 100 to 200 microM DMF. The initial decrease could be accounted for by the formation of a DMF-GSH conjugate. Dimethylfumarate treatment increased the steady state mRNA expression of the regulatory subunit of GLCL, but no increase was seen for the catalytic subunit. However, protein levels were increased for both, and the catalytic activity of GLCL was also increased. Whereas the initial decrease in GSH made hRPE cells more susceptible to oxidative damage, pretreatment with DMF under conditions that increased intracellular GSH protected hRPE cells against oxidative damage. CONCLUSIONS: These results suggest a means by which the antioxidant capability of hRPE may be augmented without direct antioxidant supplementation. Specifically, a dietary compound that conjugates with GSH can induce GSH synthesis, increase GSH concentration, and improve protection by GSH-dependent detoxification pathways in hRPE. However, the early depletion of GSH before stimulated synthesis necessitates caution in prevention strategies using dietary inducers.

Aminoacyltransferases↗
PubMed1998

Glutathione measurement in human plasma. Evaluation of sample collection, storage and derivatization conditions for analysis of dansyl derivatives by HPLC.

Literature values for human plasma GSH vary over 10-fold despite the use of apparently valid analytical procedures for GSH measurement. The purpose of this study was to develop a procedure to minimize error in sample collection, processing and storage that could contribute to such differences. HPLC with fluorescence detection of dansyl derivatives was used for quantification. The results show that collection of blood with a butterfly needle and syringe reduces overestimation due to limited hemolysis and that use of a preservation solution designed to inhibit autooxidation and enzymatic degradation allows quantitative recovery of both GSH and GSSG. Stability tests showed that non-derivatized samples were stable for at least 2 months at - 80 degrees while dansyl derivatives were stable in the dark at 0-4 degrees for 12 months. Results from 59 healthy individuals (20-43 years) provided a mean (+/-1 SD) GSH value of 2.09+/-1.14 micromolar.

Blood Specimen Collection↗
PubMed1998

Glutathione in human plasma: decline in association with aging, age-related macular degeneration, and diabetes.

Blood samples were analyzed for GSH and GSH redox state in 40 age-related macular degeneration (ARMD) patients (> 60 y), 33 non-ARMD diabetic patients (> 60 years), 27 similarly aged non-ARMD and nondiabetic individuals (> 60 years), and 19 younger individuals (< 60 years) without ARMD or diabetes. Results showed a significantly lower plasma GSH in older individuals (ARMD, diabetes, and controls) than in younger individuals (p < .01). Total GSH (GSHt) obtained following treatment with dithiothreitol was significantly lower only in diabetic cases (p < .05) but also approached significance for ARMD cases (p = .089). Estimation of redox potential indicated that the plasma GSH pool is considerably more oxidized in all of the older groups. Analyses of whole blood GSH showed that GSH was significantly lower in diabetic cases compared to the other groups, but did not reveal any difference associated with age or ARMD. In contrast, GSSG in whole blood was significantly higher in the older groups compared to the younger controls. The results suggest that in studies of age-related pathologies, oxidation of GSH may be a more important parameter than a decline in pool size, while in specific pathologies such as diabetes, both oxidation and a decline in pool size may be important.

Adult↗
PubMed1998

Inherited retinal arteriolar tortuosity with retinal hemorrhages.

BACKGROUND: Familial arteriolar tortuosity is an autosomal dominant disorder affecting the retinal arterioles. OBJECTIVES: To report a pedigree with this disorder and describe a systemic workup to determine whether this vascular abnormality is limited to the eye. RESULTS: A 58-year-old woman referred for retinal hemorrhages was found to have retinal arteriolar tortuosity of both eyes, especially in the macular area. Her 63-year-old brother had a history of retinal hemmorhages beginning at age 18 years and had similar fundoscopic examination findings. The proband had an extensive systemic workup, including magnetic resonance imaging, and cardiac and renal angiography, that failed to demonstrate any other sequelae of this inherited ocular syndrome. However, each member of the family expressing this phenotype did have hypertension. CONCLUSION: Inherited retinal arteriolar tortuosity is an autosomal dominant disorder limited to the eye, at least in this pedigree, within the sensitivity of the systemic workup we used.

Adult↗
PubMed1998

Management of submacular hemorrhage associated with retinal arterial macroaneurysms.

PURPOSE: Experience is reported with intraoperative pharmacologic lysis of recent submacular hemorrhage with tissue plasminogen activator followed by surgical drainage of the unclotted blood in patients with retinal arterial macroaneurysms. METHODS: Nine eyes (nine patients) with a recent (< or = 7 days old) submacular hemorrhage involving the center of the fovea secondary to retinal arterial macroaneurysm that were managed with recombinant tissue plasminogen activator-assisted subretinal hemorrhage evacuation, including subretinal injection of tissue plasminogen activator and removal of the liquefied blood. Patients were followed for a mean 18 +/- 7 months (range, 7 to 30 months). RESULTS: All nine eyes had improved final corrected visual acuity after surgery, and eight eyes (89%) attained a corrected visual acuity of 20/60 or better (mean, 20/40; range, 20/20 to 20/200). Final corrected visual acuity was limited to 20/200 in one eye. Two eyes developed a cataract that required surgery. CONCLUSIONS: Submacular surgery with tissue plasminogen activator-assisted thrombolysis achieved improved best-corrected visual acuity in eyes with recent submacular hemorrhage involving the center of the fovea associated with retinal arterial macroaneurysm.

Aged↗
PubMed1998

Macular hole surgery using thrombin-activated fibrinogen and selective removal of the internal limiting membrane.

PURPOSE: To evaluate a tissue sealant (autologous cryoprecipitate activated with bovine thrombin) as an adjuvant in macular hole surgery. METHODS: Sixty-nine patients with stage 2, 3, or 4 full-thickness macular hole were enrolled consecutively in a prospective pilot study. Anatomic closure of the macular holes with a single operation was the primary outcome. Fifty-eight patients had pre- and postoperative standardized measurements including best refracted visual acuity, reading speed, and contrast sensitivity. Group A patients (45) had primary macular holes; Group B patients (13) had recurrent macular holes or macular holes with "other" retinal pathology. Surgical technique was standardized and membrane dissections were optional. RESULTS: The anatomic closure rate was 80% with a minimum of 6 months follow-up. Mean improvement in visual acuity for Group A (2.9+/-0.4 lines) was significantly better than for Group B (0.8+/-0.5 lines; P = 0.008). Eyes that underwent internal limiting membrane (ILM) dissections had an anatomic closure rate of 96% (23/24), compared with 71% (32/45) in "non-ILM" cases (P = 0.034). Adverse reactions included sterile hypopyon (10%), intraretinal hemorrhage (9%), pigmentary hyperplasia (3%), and retinal detachment (3%). CONCLUSION: Tissue sealants should be evaluated as an adjuvant in macular hole surgery in a randomized clinical trial. Inflammatory reactions may occur in some patients. Internal limiting membrane dissection may improve anatomic closure rates without adversely affecting the visual acuity.

Adult↗
PubMed1997

A model for light toxicity of cultured human retinal pigment epithelium.

BACKGROUND: The effect of visible light on human retinal pigment epithelial (HRPE) cells has not been characterized under conditions that provide strict thermal control. METHODS: HRPE cells were isolated and grown to confluence. Cells were exposed to light in an incubator in which the cell temperature was controlled in response to a temperature sensor maintained in the tissue culture medium. Cells were exposed: (A) for 24, 36, and 48 h; and using a 24-h exposure followed by 24 h darkness; (B) at varying intensities of light using neutral density filters; (C) under a yellow filter; and (D) with a 12-h on-off cyclic light. RESULTS: (A) Light exposure of 36 and 48 h resulted in significant cytotoxicity, while the initial 24-h exposure did not induce subsequent cytotoxicity. (B) Light irradiance levels from 43 to 54 mW/cm2 were required to demonstrate cytotoxicity. (C) Use of a yellow filter did not eliminate the observed cytotoxicity. (D) Cyclic exposure did not result in significant cytotoxicity. CONCLUSION: This study establishes a model and basic parameters of light toxicity to HRPE cells in vitro using strict temperature control that may be used to evaluate photochemical injury to HRPE cells.

Adolescent↗
PubMed1997

Indocyanine green angiography-guided photocoagulation of choroidal neovascularization associated with retinal pigment epithelial detachment.

PURPOSE: To determine visual acuity outcome after indocyanine green angiography-guided laser photocoagulation of choroidal neovascularization associated with pigment epithelial detachment in eyes with age-related macular degeneration. METHODS: We retrospectively reviewed pretreatment and posttreatment visual acuity after laser photocoagulation to well-demarcated hyperfluorescent areas seen with indocyanine green angiography adjacent to or within pigment epithelial detachments in 20 eyes of 20 patients with age-related macular degeneration and suspected choroidal neovascularization. RESULTS: Visual acuity before and after laser photocoagulation was followed up for 3 to 24 months (median, 9 months). At 3 months after laser photocoagulation, visual acuity had improved 2 or more Snellen lines in two eyes (10%), worsened by 2 or more lines in 10 (50%), and remained unchanged in eight of 20 (40%). By 6 months after laser photocoagulation, visual acuity had improved by 2 or more lines in two eyes (12%), worsened by 2 or more lines in nine (53%), and remained unchanged in six of 17 (35%). At 9 months after laser photocoagulation, visual acuity had improved by 2 or more lines in one eye (9%), worsened by 2 or more lines in nine (82%), and remained unchanged in one of 11 (9%). CONCLUSIONS: Indocyanine green angiography-guided laser photocoagulation may temporarily stabilize visual acuity in some eyes with choroidal neovascularization associated with pigment epithelial detachments, but final visual acuity decreases with time.

Aged↗
PubMed1997

Retinal vein occlusion and transient monocular visual loss associated with hyperhomocystinemia.

PURPOSE: To report a 24-year-old man with bilateral central retinal vein occlusions who had preceding episodes of prolonged transient monocular visual loss during which ophthalmoscopic findings were not suggestive of vein occlusion. METHOD: Case report. RESULT: Extensive hematologic studies for causes of vein occlusion were unremarkable with the exception of increased plasma homocysteine in the patient and in his asymptomatic father. CONCLUSIONS: Impending vein occlusion should be considered in the differential diagnosis of transient monocular visual loss regardless of ophthalmoscopic appearance, and hyperhomocystinemia should be considered as a possible cause of retinal vein occlusion.

Adult↗
PubMed1997

A system for classifying mechanical injuries of the eye (globe). The Ocular Trauma Classification Group.

PURPOSE: To develop a classification system for mechanical injuries of the eye. METHODS: The Ocular Trauma Classification Group, a committee of 13 ophthalmologists from seven separate institutions, was organized to discuss the standardization of ocular trauma classification. To develop the classification system, the group reviewed trauma classification systems in ophthalmology and general medicine and, in detail, reports on the characteristics and outcomes of eye trauma, then established a classification system based on standard terminology and features of eye injuries at initial examination that have demonstrated prognostic significance. RESULTS: This system classifies both open-globe and closed-globe injuries according to four separate variables: type of injury, based on the mechanism of injury; grade of injury, defined by visual acuity in the injured eye at initial examination; pupil, defined as the presence or absence of a relative afferent pupillary defect in the injured eye; and zone of injury, based on the anteroposterior extent of the injury. This system is designed to be used by ophthalmologists and nonophthalmologists who care for patients or conduct research on ocular injuries. An ocular injury is classified during the initial examination or at the time of the primary surgical intervention and does not require extraordinary testing. CONCLUSIONS: This classification system will categorize ocular injuries at the time of initial examination. It is designed to promote the use of standard terminology and assessment, with applications to clinical management and research stud ies regarding eye injuries.

Adult↗
PubMed1996

Postoperative hypopyon after intravitreal bovine thrombin for macular hole surgery.

PURPOSE: We used intravitreal autologous fibrinogen with bovine thrombin for the surgical closure of macular holes in 60 cases. METHODS: Pars plana vitrectomy with separation of the posterior cortical vitreous was performed after air/fluid exchange. One to two drops each of autologous fibrinogen and bovine thrombin (20 to 80 U) were instilled in each patient. RESULTS: Five (8%) of 60 patients developed a hypopyon without unusual pain on the first postoperative day. Inflammation responded to frequent topical corticosteroids within 48 to 72 hours. CONCLUSION: Postvitrectomy hypopyon after the use of bovine thrombin may represent an immune reaction that must be differentiated from endophthalmitis. We recommend careful observation and frequent topical corticosteroids.

Adult↗
PubMed1996

Subfoveal choroidal neovascularization in punctate inner choroidopathy. Surgical management and pathologic findings.

PURPOSES: To evaluate submacular surgery for the management of subfoveal choroidal neovascularization in punctate inner choroidopathy, to describe the histopathology and ultrastructure of the excised subretinal tissue, and to propose a staging system that characterizes the development of choroidal neovascularization with associated subretinal fibrosis. METHODS: The authors reviewed the records of five patients (6 eyes) with punctate inner choroidopathy who underwent submacular surgery for subfoveal choroidal neovascularization. Surgical specimens were examined using light and transmission electron microscopy. RESULTS: Visual improvement was noted postoperatively in all six eyes, with follow-up ranging from 8 to 36 months (median, 14 months). Recurrences (6 in 4 eyes) were common. Five of the six recurrences required additional procedures: three were managed surgically, two with laser photocoagulation, and one with observation. "Bridging" of separate foci of choroidal neovascularization resulted in stellate or "dumbbell-shaped" areas of subretinal fibrosis in four of six eyes. Histopathologic evaluation of the excised tissue showed endothelial-lined vascular channels, retinal pigment epithelium, lymphocytes, plasma cells, fibrocytes, collagen fragments, and rarely, outer retinal elements. CONCLUSIONS: Subfoveal choroidal neovascularization in punctate inner choroidopathy may be managed with submacular surgery. Recurrences are common and may result in substantial loss of vision. Choroidal neovascular membranes with an accompanying fibrotic reaction are responsible for the stellate or dumbbell-shaped areas of subretinal fibrosis. No beneficial effect was demonstrated using corticosteroid treatment of the choroidal neovascularization.

Adult↗
PubMed1996

Ocular nail gun injuries.

PURPOSE: Penetrating ocular trauma resulting from nails can have disastrous visual consequences. Ocular nail gun injuries occur when a nail propelled at high velocity penetrates the globe. The authors report four consecutive patients with ocular injuries resulting from nail guns. METHODS: Four patients with ocular nail gun injuries are described: one with scleral penetrating injury, one with corneal penetrating injury, and two with perforating (through- and-through) injuries of the globe. RESULTS: Three of the four patients recovered good visual acuity after surgical intervention. CONCLUSION: Although dependent on the site of impact, the visual prognosis may be less severe than expected because the nail penetrates the eye at a high velocity such that there are less contusive forces. Adherence to safety precautions involving the use of nail guns as well as the obligatory use of safety glasses should reduce the incidence of these injuries.

Accidents, Occupational↗
PubMed1995

Variability in glutathione-dependent detoxication in vivo and its relevance to detoxication of chemical mixtures.

Glutathione (GSH) has multiple functions in detoxication and its depletion has been associated with an increased risk of chemical toxicity. Because GSH can be depleted by different agents, combinations of compounds in chemical mixtures are likely to enhance risk over that seen with individual chemicals. Our studies have focussed on factors affecting the status of GSH in humans. In addition, we have utilized animals models and cell culture systems to understand the role of GSH in protection against chemical injury. Results of these studies show that, while large variations in sulfur amino acid content occur in the human diet, these variations are not correlated simply with GSH levels in vivo as reflected in the blood plasma pool. However, plasma levels of GSH do vary with gender, age, race and dietary habits, and these factors could affect the risk of toxicity in individuals exposed to chemical mixtures. In animal studies, we found that extracellular pools of GSH, including the blood plasma, lung-lining fluid and small intestinal lumen can be very important in protection against chemically induced injury. These pools can function to detoxify chemicals extracellularly, supply GSH and its precursors to cells and protect the extracellular surface of the plasma membrane from damage. Finally, endogenous gene-activated mechanisms of cell death which produce the characteristic morphology of apoptosis are susceptible to thiol-disulfide redox regulation. Perturbations in GSH status induced by chemical mixtures could alter this regulation and lower the threshold for chemically induced cell death by apoptosis. Thus, in vivo GSH status could be an important determinant of toxicity from chemical mixtures and may be useful as a biomarker for such risk.

Animals↗