Biomedical subjects

Steven E Feldon

Publications and source records attributed to Steven E Feldon.

10 recordsLinked to original sources

PubMed2006

Development and validation of a computerized expert system for evaluation of automated visual fields from the Ischemic Optic Neuropathy Decompression Trial.

BACKGROUND: The objective of this report is to describe the methods used to develop and validate a computerized system to analyze Humphrey visual fields obtained from patients with non-arteritic anterior ischemic optic neuropathy (NAION) and enrolled in the Ischemic Optic Neuropathy Decompression Trial (IONDT). The IONDT was a multicenter study that included randomized and non-randomized patients with newly diagnosed NAION in the study eye. At baseline, randomized eyes had visual acuity of 20/64 or worse and non-randomized eyes had visual acuity of better than 20/64 or were associated with patients refusing randomization. Visual fields were measured before treatment using the Humphrey Field Analyzer with the 24-2 program, foveal threshold, and size III stimulus. METHODS: We used visual fields from 189 non-IONDT eyes with NAION to develop the computerized classification system. Six neuro-ophthalmologists ("expert panel") described definitions for visual field patterns defects using 19 visual fields representing a range of pattern defect types. The expert panel then used 120 visual fields, classified using these definitions, to refine the rules, generating revised definitions for 13 visual field pattern defects and 3 levels of severity. These definitions were incorporated into a rule-based computerized classification system run on Excel(R) software. The computerized classification system was used to categorize visual field defects for an additional 95 NAION visual fields, and the expert panel was asked to independently classify the new fields and subsequently whether they agreed with the computer classification. To account for test variability over time, we derived an adjustment factor from the pooled short term fluctuation. We examined change in defects with and without adjustment in visual fields of study participants who demonstrated a visual acuity decrease within 30 days of NAION onset (progressive NAION). RESULTS: Despite an agreed upon set of rules, there was not good agreement among the expert panel when their independent visual classifications were compared. A majority did concur with the computer classification for 91 of 95 visual fields. Remaining classification discrepancies could not be resolved without modifying existing definitions. Without using the adjustment factor, visual fields of 63.6% (14/22) patients with progressive NAION and no central defect, and all (7/7) patients with a paracentral defect, worsened within 30 days of NAION onset. After applying the adjustment factor, the visual fields of the same patients with no initial central defect and 5/7 of the patients with a paracentral defect were seen to worsen. CONCLUSION: The IONDT developed a rule-based computerized system that consistently defines pattern and severity of visual fields of NAION patients for use in a research setting.

Automation↗

PubMed2006

More than structural cells, fibroblasts create and orchestrate the tumor microenvironment.

The tumor microenvironment comprises many cell types including infiltrating immune cells such as lymphocytes, endothelial cells and a complex stroma consisting mainly of fibroblasts. Fibroblasts are heterogeneous and consist of Thy-1+ and Thy-1- subsets that define different biosynthetic and differentiation potential. They produce mediators linked to carcinogenesis and metastasis, including Cox-2 and PGE2, both of which are also increased in most cancers. This review will highlight the emerging role of the complex fibroblastic stroma in establishing a microenvironment supporting malignant transformation, tumor growth and attenuation of host anti-tumor immune responses.

Animals↗

PubMed2006

Activated human T lymphocytes express cyclooxygenase-2 and produce proadipogenic prostaglandins that drive human orbital fibroblast differentiation to adipocytes.

The differentiation of preadipocyte fibroblasts to adipocytes is a crucial process to many disease states including obesity, cardiovascular, and autoimmune diseases. In Graves' disease, the orbit of the eye can become severely inflamed and infiltrated with T lymphocytes as part of the autoimmune process. The orbital fibroblasts convert to fat-like cells causing the eye to protrude, which is disfiguring and can lead to blindness. Recently, the transcription factor peroxisome proliferator activated receptor (PPAR)-gamma and its natural (15d-PGJ2) and synthetic (thiazolidinedione-type) PPAR-gamma agonists have been shown to be crucial to the in vitro differentiation of preadipocyte fibroblasts to adipocytes. We show herein several novel findings. First, that activated T lymphocytes from Graves' patients drive the differentiation of PPAR-gamma-expressing orbital fibroblasts to adipocytes. Second, this adipogenic differentiation is blocked by nonselective small molecule cyclooxygenase (Cox)-1/Cox-2 inhibitors and by Cox-2 selective inhibitors. Third, activated, but not naïve, human T cells highly express Cox-2 and synthesize prostaglandin D2 and related prostaglandins that are PPAR-gamma ligands. These provocative new findings provide evidence for how activated T lymphocytes, through production of PPAR-gamma ligands, profoundly influence human fibroblast differentiation to adipocytes. They also suggest the possibility that, in addition to the orbit, T lymphocytes influence the deposition of fat in other tissues.

Adipocytes↗

PubMed2005

Isolation and phenotypic characterization of lung fibroblasts.

Primary fibroblasts represent a heterogeneous population of cells that can be separated into subsets on the basis of cell surface markers such as Thy-1. Deriving fibroblasts initially involves obtaining tissue explants from tissues such as the lung, heart, cornea, skin, and orbit. The tissue is mechanically dissociated and cells are allowed to proliferate from the fragments. Following establishment of a primary culture of fibroblasts, it is necessary to characterize the new strain of cells to ensure their purity and fibroblastic phenotype using immunofluorescence and immunohistochemistry to detect the presence or absence of cell-specific surface markers. Characterizing the cells as expressing or lacking Thy-1 can also be performed by immunofluorescence in concert with microscopy or by flow cytometry using an anti-human Thy-1 antibody. In addition, fibroblasts may be sorted according to their expression of Thy-1 by fluorescence-activated cell sorting and/or magnetic beading; use of these techniques can yield greater than 99% purity. Once separated, the pure Thy-1 expressing or lacking fibroblast subsets can be propagated. These subsets can then be used for experimentation to determine functional differences between fibroblasts derived from normal and pathological tissue such as scarred lung.

Animals↗

PubMed2004

A novel ELISpot method for adherent cells.

The purpose of this study was to develop an enzyme-linked immunospot assay (ELISpot assay) that can be used with human adherent cells. While standard enzyme-linked immunosorbent assays (ELISAs) are available and widely used and ELISpot assays are used for nonadherent lymphocytes, no ELISpot assay has been developed for adherent cells. We used primary human fibroblasts from four different tissues (myometrium, lung, gingiva, and orbit), either unstimulated or interleukin (IL)-1beta-activated, to evaluate an ELISpot assay. Antibody pairs for IL-6 and IL-8 were used and results were compared to a standard ELISA. We found that we could reliably detect IL-6 and IL-8 spots with as few as 10 fibroblasts. Optimal cell numbers were 50 cells per well incubated for 8 h, although spots appeared as early as 2 h after incubation. Spots were absent when cells, primary, or secondary anti-cytokine antibodies were omitted from the protocol. Spot number and size can be ascertained using current automated ELISpot reader technology. The frequency of IL-6 and IL-8-producing human fibroblasts could also be determined. For example, 60% of the lung fibroblasts express IL-6, but IL-8 can be detected from only 40% of the cells. Approximately 80% of the human orbital fibroblasts make IL-6, whereas approximately 50% generate IL-8 following IL-1beta stimulation. These new findings show that fibroblasts from different human tissues display different frequencies of cytokine production and this further supports the concept of fibroblast diversity. The sensitivity of this new ELISpot assay is adequate for cytokine detection in just a few cells, unlike the standard ELISA. It should permit ascertaining the frequency of fibroblasts and other adherent cells that produce cytokines and, if desired, can be used in tandem with a standard ELISA to determine total cytokine produced. Moreover, the assay is suitable for normal human adherent cells that are often short-lived and difficult to cultivate.

Cell Adhesion↗

PubMed2004

Computerized expert system for evaluation of automated visual fields from the Ischemic Optic Neuropathy Decompression Trial: methods, baseline fields, and six-month longitudinal follow-up.

PURPOSE: To validate a computerized expert system evaluating visual fields in a prospective clinical trial, the Ischemic Optic Neuropathy Decompression Trial (IONDT). To identify the pattern and within-pattern severity of field defects for study eyes at baseline and 6-month follow-up. DESIGN: Humphrey visual field (HVF) change was used as the outcome measure for a prospective, randomized, multicenter trial to test the null hypothesis that optic nerve sheath decompression was ineffective in treating nonarteritic anterior ischemic optic neuropathy and to ascertain the natural history of the disease. METHODS: An expert panel established criteria for the type and severity of visual field defects. Using these criteria, a rule-based computerized expert system interpreted HVF from baseline and 6-month visits for patients randomized to surgery or careful follow-up and for patients who were not randomized. RESULTS: A computerized expert system was devised and validated. The system was then used to analyze HVFs. The pattern of defects found at baseline for patients randomized to surgery did not differ from that of patients randomized to careful follow-up. The most common pattern of defect was a superior and inferior arcuate with central scotoma for randomized eyes (19.2%) and a superior and inferior arcuate for nonrandomized eyes (30.6%). Field patterns at 6 months and baseline were not different. For randomized study eyes, the superior altitudinal defects improved (P = .03), as did the inferior altitudinal defects (P = .01). For nonrandomized study eyes, only the inferior altitudinal defects improved (P = .02). No treatment effect was noted. CONCLUSIONS: A novel rule-based expert system successfully interpreted visual field defects at baseline of eyes enrolled in the IONDT.

Aged↗

PubMed2003

The Eger Macular Stressometer: pilot study.

PURPOSE: To evaluate the sensitivity of the Eger Macular Stressometer (EMS) for early screening of age-related macular degeneration (AMD) in a clinical practice. We examined the null hypothesis that AMD eyes have EMS recovery times (RTs) that do not differ from eyes with cataract, diabetic retinopathy, or glaucoma. DESIGN: The design of this study was a nonrandomized clinical trial. METHODS: Ninety-two eyes from 92 patients with vision 20/80 or better, age 50 and older, of either gender, and any ethnic origin, were recruited into one of four groups: AMD (30 eyes), normal or mild cataract (30 eyes), diabetic retinopathy (16 eyes), and glaucoma (16 eyes). Recovery times were obtained with the EMS, according to manufacturer's instructions. RESULTS: The mean (SD) [median] RT for the AMD group was 11.8 (7.6) [9] seconds, the normal/cataract group 10.0 (4.3) [9] seconds, the diabetic retinopathy group 8.4 (3.0) [8] seconds, and glaucoma group 8.6 (2.4) [8] seconds. Recovery time did not appear to be related to group (P =.58), age (P =.50), visual acuity (P =.52), or sex (P =.23). CONCLUSIONS: We found EMS RT distributions did not differ between AMD, cataract, diabetic retinopathy, and glaucoma groups. The EMS in its current form is not a sensitive screening tool for AMD. Further testing is needed to examine EMS sensitivity with other macular diseases such as central serous choroidopathy and diabetic macular edema.

Aged↗

PubMed2003

Surgical quality assurance in the Ischemic Optic Neuropathy Decompression Trial (IONDT).

The purpose of this article is to report the methods and results of the surgical quality assurance program associated with the Ischemic Optic Neuropathy Decompression Trial (IONDT). A surgical quality assurance committee developed and implemented a quality assurance program for a randomized clinical trial requiring surgical intervention. A surgical technique questionnaire was administered at two times during the study course, and maintenance of surgeon certification required submission and approval of a masked videotape of an optic nerve sheath decompression surgery by each study surgeon. Surgical quality was assessed through completion of surgical report forms and standardized, masked review of operative notes. Rates of compliance and intra- and interreviewer agreement were assessed for each aspect of the program. Twenty-five of 32 surgeons (81%) successfully completed and maintained certification. Item agreement varied from 21-92% among reviewers of satisfactory videotapes and 22-89% on unsatisfactory videotapes. Intrarater agreement for videotape acceptability was 11 of 13 (85%), and for specific surgical steps, 147 of 182 (81%). Operative notes were submitted for 123 of 125 (98%) patients receiving surgery. Interrater agreement on individual items ranged from 73-100%. Classification of individual items was identical on first and second review for 1285 of 1344 (95.6%) items. Overall agreement for individual reviewers was 93.8-97.8%. We conclude that use of a small peer review committee, which developed and oversaw a quality assurance program, allowed for consistent certification and monitoring of surgical performance. This in turn increased the credibility of the IONDT results, which demonstrated no difference in outcome between operated and unoperated groups of patients.

Certification↗

PubMed2003

Sweep visual evoked potential evaluation of contrast sensitivity in Alzheimer's dementia.

PURPOSE: The purpose of this study was to evaluate primary afferent visual pathway function by objectively testing contrast sensitivity in persons with Alzheimer's dementia (AD), using a sweep visual evoked potential technique. METHODS: Twenty-five patients, 16 with AD and 9 elderly control (EC) subjects, were enrolled from the University of Southern California Rancho Los Amigos Medical Center. The patients with AD had clinical dementia ratings ranging from 0.5 to 3, corresponding to mild to moderate disease. All participants underwent refraction and screening for ophthalmic disease. Subjects were evaluated with the sweep visual evoked potential technique. Each trial consisted of logarithmically increasing contrast over a 10-second period. Subjects were evaluated monocularly at spatial frequencies of 1, 5, and 8 cyc/deg. Patients were not required to integrate and respond to stimuli. RESULTS: Mean contrast sensitivity thresholds were significantly higher in patients with AD than in EC subjects. The mean contrast sensitivities in the AD group were 4.0%, 9.6%, and 18.6%, at 1, 5, and 8 cyc/deg, respectively. The corresponding sensitivities in the EC group were 2.1%, 5.3%, and 11.4%, at 1, 5, and 8 cyc/deg, respectively. These threshold differences were significant at probabilities of 0.01, 0.05, and 0.07. There was no correlation between clinical dementia ratings and reduction of contrast sensitivity thresholds. Confounding factors such as age, gender, nuclear sclerosis, and visual acuity were evaluated. Visual acuity was the only factor significantly different between AD responders and AD nonresponders at 1 and 5 cyc/deg. CONCLUSIONS: These results suggest patients with AD have deficits in contrast sensitivity attributable to dysfunction of the primary afferent visual pathway.

Aged↗

PubMed2002

Correction of restricted extraocular muscle motility in surgical management of strabismus in graves' ophthalmopathy.

OBJECTIVE: To compare the success rates for strabismus surgery designed to correct limitation of duction with surgery designed to correct deviation in patients with Graves' ophthalmopathy. DESIGN: Retrospective nonrandomized comparative trial. PARTICIPANTS: One hundred thirty-seven patients with Graves' ophthalmopathy who had undergone at least one extraocular muscle surgery were divided into two groups: those whose first surgery occurred before June 1997 (control group) and those whose first surgery occurred in June 1997 or thereafter (case group). INTERVENTIONS: Extraocular muscle surgery primarily directed at either correcting deviation (control group) or correcting limitation of ductions (case group). MAIN OUTCOME MEASURES: Postoperative deviations in the primary position were measured in prism diopters 30 to 180 days after surgery. A postoperative deviation of less than 5 diopters was considered a successful surgical outcome. RESULTS: Patients undergoing strabismus surgery specifically designed to correct limitation of duction achieved a 74% success rate compared with a 44% success rate in the control group (P < 0.01). Furthermore, the rate of reoperation in this group was only 27% compared with 44% in the control group (P < 0.04). CONCLUSIONS: Compared with surgery aimed primarily at the correction of deviation, extraocular muscle surgery tailored to address restriction of ductions in patients with Graves' ophthalmopathy is associated with improved surgical success of initial realignment and with a lower rate of reoperation

Eye Movements↗