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Biomedical subjects

Daniel M Miller

Publications and source records attributed to Daniel M Miller.

5 recordsLinked to original sources

Diagnostic testing of vitrectomy specimens.

PURPOSE: To assess the usefulness of diagnostic tests that are performed on vitrectomy specimens from patients with suspected lymphoma or infection. DESIGN: Noncomparative, retrospective, interventional case series. METHODS: Seventy-eight consecutive patients (84 eyes) underwent pars plana vitrectomy for diagnostic purposes. Vitrectomy with cytologic, cytofluorographic, or microbiologic analysis of vitreous samples was performed. The main outcome measures were the efficiency of diagnostic procedure and positive and negative predictive values (PPV and NPV). RESULTS: There were 28 patients (33 eyes) with suspected intraocular lymphoma and 50 patients (51 eyes) with suspected infection, which was subdivided into chronic endogenous endophthalmitis, atypical chorioretinitis, or chronic postoperative inflammation. Vitreous testing led to a diagnosis in 48 of 78 patients (61.5%); 14 patients with a final diagnosis of lymphoma/leukemia, and 34 patients with a final diagnosis of infection. When preoperative indication was compared with final clinical diagnosis, the efficiency of the diagnostic procedure of cytologic evaluation, flow cytometry, and bacterial/fungal culture was 67%, 79%, and 96%, respectively. For lymphoma, the PPV of cytologic evaluation was 100% and the NPV 60.9%. For infection, the PPV of bacterial/fungal culture was 100% and the NPV 94.9%. CD22+ B lymphocytes >or=20% of total cells on cytofluorographic analysis had a PPV of 88% for lymphoma. A cytofluorographic CD4:CD8 T-lymphocyte ratio >or=4 had a PPV of 70% for immunologically mediated uveitis. Surgical complications were rare and manageable. CONCLUSION: Diagnostic vitrectomy in selected patients with carefully planned testing is an effective means of supporting diagnoses in intraocular lymphoma, chronic intraocular infections, and atypical chorioretinitis. Flow cytometry quantitates the percentages and ratios of various cell types and is helpful in contrasting intraocular lymphoma with immunologically mediated uveitis.

Adult↗

Pars plana lensectomy and intraocular lens implantation in pediatric radiation-induced cataracts in retinoblastoma.

OBJECTIVE: To investigate visual outcomes, surgical complications, and tumor recurrence among children with retinoblastoma (RB) undergoing pars plana lensectomy, vitrectomy, and simultaneous intraocular lens insertion for radiation-related cataract secondary to external beam radiotherapy (EBRT). DESIGN: Retrospective, noncomparative, consecutive case series. METHODS: The medical records for all patients treated with pars plana lensectomy, vitrectomy, and posterior chamber intraocular lens implantation for radiation-induced cataract after EBRT for RB at a single institution between January 1, 1990, and December 31, 2000, were reviewed. PARTICIPANTS: The study included 16 eyes of 12 children with Reese-Ellsworth stage V RB. MAIN OUTCOME MEASURES: Visual acuity, surgical and postoperative complications, postoperative refraction, and tumor recurrence. RESULTS: The median age at diagnosis of RB was 6 months (range, 1-49 months). All patients received EBRT as primary treatment and experienced radiation-induced cataracts. The median interval from RB diagnosis to cataract surgery was 42 months (range, 28-95 months). Preoperative mean visual acuity was 20/400, with 12 of 16 eyes (75%) having macular tumor involvement. All patients underwent pars plana lensectomy, vitrectomy, and posterior chamber intraocular lens insertion. Vitreous samples were evaluated by cytopathologic examination, and no viable tumor cells were identified in any of the vitreous specimens. Postoperative complications included transient cystoid macular edema in 5 eyes (31%) and iridocyclitis in 3 eyes (19%). The mean follow-up after cataract surgery was 66 months (range, 30-94 months). Final visual acuity was 20/40 or better in 11 of 16 eyes (69%). No late intraocular recurrence, orbital tumors, or metastatic disease was noted in this study. CONCLUSIONS: Pars plana lensectomy, vitrectomy, and simultaneous intraocular lens implantation is an effective means of managing EBRT-induced cataracts in eyes with previously treated RB. There was no evidence of active tumor in eyes undergoing surgery at least 28 months after the diagnosis and commencement of therapy for RB, and no late intraocular, orbital, or metastatic tumors were detected. Visual acuity was limited by the presence of primary macular tumor pathologic features in a subset of patients, but final vision better than 20/400 may be achieved in these eyes.

Cataract↗

The association of prior cytomegalovirus infection with neovascular age-related macular degeneration.

PURPOSE: To determine if prior exposure to pathogens associated with vascular disease, cytomegalovirus, Chlamydia pneumoniae, and Helicobacter pylori correlates with neovascular age-related macular degeneration (AMD). DESIGN: An experimental study. METHODS SETTING: Institutional. Bascom Palmer Eye Institute, October 2001 to December 2002. PATIENT POPULATION: 150 patients (47 neovascular amd, 36 dry amd, and 67 non-amd controls) were included in the study. exclusion criteria included hiv infection, malignancy, recent acute illness requiring hospitalization within 6 months, or immunosuppressive illness. PROCEDURE: Serum samples were obtained for analysis of cytomegalovirus, chlamydia pneumoniae, and helicobacter pylori igg antibody titers by elisa. MAIN OUTCOME MEASURE: Comparison of the distribution of igg titers between patients with wet amd, dry amd, and controls. RESULTS: The average cytomegalovirus IgG titer was higher in patients with wet AMD versus controls (p = 0.02, Student t-test, two-tailed) and patients with dry AMD (p = 0.06). Twenty-six (55%) of 47 subjects with wet AMD had high cytomegalovirus IgG titers compared with 14 (39%) of 36 patients with dry AMD (odds ratio [OR] = 2.23, 95% confidence interval [CI] = 0.77 to 6.44) and 23 (34%) of 67 control patients (OR = 2.49, 95% CI = 0.98 to 6.33). There was no major difference in the distribution of titers for Chlamydia pneumoniae IgG and Helicobacter pylori IgG in wet and dry AMD patients. Five of 47 patients with wet AMD (11%) had high antibody titers to all three pathogens, compared with only 1 of 36 patients with dry AMD (3%) (OR = 4.17, 95% CI = 0.46 to 37.36). CONCLUSIONS: There was a significant association of high cytomegalovirus IgG titer with neovascular AMD compared with dry AMD and control patients. Chronic infection with cytomegalovirus may be a novel risk factor for the progression from dry to neovascular AMD.

Aged↗

Human cytomegalovirus disrupts constitutive MHC class II expression.

CD8(+) and CD4(+) T lymphocytes are important in controlling human CMV (HCMV) infection, but the virus has evolved protean mechanisms to inhibit MHC-based Ag presentation and escape T lymphocyte immunosurveillance. Herein, the interaction of HCMV with the MHC class II Ag presentation pathway was investigated in cells stably transfected with class II transactivator. Flow cytometry experiments demonstrate that HCMV infection decreases cell-surface MHC class II expression. HCMV down-regulates MHC class II surface expression without a significant effect on class II RNA or steady-state protein levels. SDS-stability and confocal microscopy experiments demonstrate normal levels of steady-state peptide-loaded class II molecules in infected cells and that class II molecules reach late endosomal and HLA-DM positive peptide-loading compartments. However, MHC class II positive vesicles are retained in an abnormal perinuclear distribution. Finally, experiments with a mutant HCMV strain demonstrate that this novel mechanism of decreased MHC class II expression is not mediated by one of the known HCMV immunomodulatory genes. These defects in MHC class II expression combined with previously identified CMV strategies for decreasing MHC class I expression enables infected cells to evade T lymphocyte immunosurveillance.

Antigens, Differentiation, B-Lymphocyte↗