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Biomedical subjects

Jay M Stewart

Publications and source records attributed to Jay M Stewart.

At least 19 recordsLinked to original sources
PubMed2026

Metagenomic Deep Sequencing Identifies Gene Mutations Associated with Chemotherapeutic Resistance in Vitreoretinal Lymphoma.

PURPOSE: To identify gene mutations associated with chemotherapeutic resistance in patients with vitreoretinal lymphoma (VRL) using metagenomic deep sequencing (MDS) of intraocular specimens. METHODS: Patients with VRL confirmed by cytopathology and immunohistochemistry, flow cytometry, and/or polymerase chain reaction for MYD88, were included. Intraocular specimens underwent MDS of the host genome. Gene mutations were identified and cross-referenced with the Catalogue of Somatic Mutations in Cancer database to determine associations with chemotherapeutic resistance. RESULTS: Forty-nine patients with VRL underwent MDS, with six specimens from four patients revealing eight gene mutations associated with chemotherapeutic resistance. Four specimens from three patients harbored mutations associated with methotrexate resistance, the mainstay of VRL treatment. In one patient, serial sampling from the initial vitrectomy and two subsequent recurrences revealed distinct resistance-associated mutations at each time point. Despite multi-agent therapy including rituximab, consolidation regimens, and lenalidomide, this patient ultimately succumbed to the disease, whereas the other three patients remained in long-term remission. CONCLUSIONS: Our findings demonstrated that specific gene mutations associated with chemotherapeutic resistance may be harbored by VRL. The detection of different resistance mutations at sequential time points in one patient may reflect clonal selection, treatment pressure, or variable detection sensitivity. The ability to easily sample ocular fluid and detect different mutations associated with tumor recurrence or persistence may provide insights into tumor pathogenesis and could inform prognosis and influence treatment decisions. These findings establish a foundation for developing targeted PCR assays for identified resistance genes, which could transform clinical practice in VRL.

Chemotherapeutic resistance-associated mutations↗
PubMed2006

A new model of experimental subretinal neovascularization in the rabbit.

Existing animal models of choroidal neovascularization (CNV) present several problems: they are hard to reproduce, they are inefficient, and the CNV created is not sustainable. The purpose of this study is to develop a highly efficient, reliable, sustainable rabbit model of CNV to facilitate the study of anti-angiogenic and anti-proliferative therapies for ocular diseases. Twenty-two pigmented rabbits were used in this study. Eleven rabbits received subretinal injections of either 10 microl of Matrigel with 500 ng of vascular endothelial growth factor (VEGF) or 20 microl of Matrigel with 750 ng of VEGF; eight rabbits received subretinal injections of either 10 or 20 microl of Matrigel only; three rabbits used as controls received subretinal injections of 20 microl phosphate-buffered saline (PBS) alone. Fundus photography, fluorescein angiography, optical coherence tomography, and histologic examinations were performed 1, 2, 4, and 9 weeks after injection. All experimental eyes showed angiographic leakage within this localized area 1 week after injection. The amount of leakage usually increased at weeks 2 and 4 and, in most cases, persisted at week 9. Control eyes demonstrated no leakage at any time point. Optical coherence tomography of treated eyes showed subretinal fluid and the presence of a lesion, possibly vascular or fibrotic, at the site of the leakage. Histologic analysis confirmed the presence of new subretinal blood vessels in the areas of Matrigel deposit. In conclusion, this novel method provides a highly reproducible, reliable, and sustainable rabbit model of experimental choroidal neovascularization. Such a model may prove useful for screening new anti-angiogenic therapies in a larger animal eye.

Animals↗
PubMed2006

Development, implantation, in vivo elution, and retrieval of a biocompatible, sustained release subretinal drug delivery system.

A biocompatible, sustained-release subretinal drug-delivery platform was developed to overcome the therapeutic accessibility limitations of current retinal disease treatments. The prototype implants were fabricated by coating nitinol, poly(methyl methacrylate) or chromic gut core filaments, with a drug-eluting polymer matrix. The polymer coatings are manufactured and coated by SurModics. The coating is a mixture of poly(butyl methacrylate) and poly(ethylene-co-vinyl acetate). The drug is either triamcinolone acetonide or sirolimus. The rods were successfully implanted into the subretinal space of 20/24 rabbits. Four rabbits were lost to early surgery from a dysfunctional infusion line and hemorrhage. No serious complications were observed during the 4-week follow-up period. Slight conjunctival redness was reported in all rabbits by 1-day follow-up, but the redness had subsided by the following week. Intraocular lens touch occurred in six rabbits during the implantations; of these, four had a lensectomy at the time of surgery, and the remaining two developed cataract. Corneal edema developed in three rabbits by 1-week follow-up, but subsided within 2 weeks. Initial observations of the implantation and elution characteristics revealed that the implants are well tolerated by the retinal tissue and that the implant can elute triamcinolone acetonide for a period of at least 4 weeks without eliciting an inflammatory response or complications. There were adverse clinical indications with the sirolimus-loaded implants at the delivered dose. Device retrieval required an uncomplicated surgical procedure, and revealed no associated or adherent tissue. Implant drug content analysis and opacity changes to the polymer matrix coating following retrieval demonstrated the sustained elution of the drug.

Animals↗
PubMed2006

Bacterial endophthalmitis after resident-performed cataract surgery.

PURPOSE: To determine if there is an increased rate of postoperative bacterial endophthalmitis after resident-performed cataract extraction relative to the reported rates of experienced surgeons. DESIGN: Retrospective, observational case series. METHODS: The operative reports of the resident-performed cataract surgeries at San Francisco General Hospital between 1983 and 2002 were reviewed. Cases of culture-positive bacterial endophthalmitis and vitreous loss were identified. RESULTS: Between 1983 and 2002, three cases (0.11%) of culture-positive bacterial endophthalmitis occurred after 2718 resident-performed cataract extractions. The overall vitreous loss rate was 6.7%. Two endophthalmitis cases were acute (Staphylococcus epidermidis, Streptococcus viridans), presenting within five days of surgeries complicated by vitreous loss, and one case was delayed-onset (Corynebacterium species) after Nd:YAG posterior capsulotomy after uncomplicated cataract extraction. CONCLUSIONS: Despite higher rates of vitreous loss, the rate of endophthalmitis following resident-performed cataract surgery remains comparable with the rates of more experienced surgeons.

Cataract Extraction↗
PubMed2006

Ciliary body edema.

Explore the source record for details and available documents.

Anterior Chamber↗
PubMed2005

Prevalence, clinical features, and causes of vision loss among patients with ocular toxocariasis.

BACKGROUND: To describe the prevalence, clinical features, and causes of vision loss among patients with ocular toxocariasis seen at a uveitis referral center. METHODS: A review was completed of the charts of patients with ocular toxocariasis who were examined between 1977 and 1996 at the Francis I. Proctor Foundation of the University of California at San Francisco. The prevalence of ocular toxocariasis among all uveitis patients seen at the center was determined. Demographic features, symptoms, and signs in all patients were evaluated. RESULTS: Ocular toxocariasis occurred in 22 (1.0%) of 2,185 uveitis patients. The mean patient age was 16.5 years. Inflammation was usually unilateral (90.9%). Toxocara uveitis presented as a granuloma in the peripheral retina in 50% of cases, as a granuloma in the macula in 25% of cases, and as a moderate to severe vitreous inflammation mimicking endophthalmitis in 25% cases. The primary causes of vision loss were vitritis (52.6%), cystoid macular edema (47.4%), and traction retinal detachment (36.8%). CONCLUSIONS: Ocular toxocariasis is an uncommon cause of uveitis that mainly affects younger patients. Inflammation is typically unilateral and presents as either a granuloma in the peripheral or posterior retina or a moderate to severe vitreous inflammation mimicking endophthalmitis.

Adolescent↗
PubMed2005

Sensitivity of bone marrow aspirates in the diagnosis of visceral leishmaniasis.

Bone marrow aspirates are believed to provide a safer but less sensitive method in the diagnosis of visceral leishmaniasis (VL) compared with splenic aspirates. We examined the effect of the number of fields and the time of observation on bone marrow smear sensitivity and compared it to our experience with spleen aspiration. Bone marrow smears of 98 patients and splenic aspirates from 120 patients were examined. Among 87 patients with VL, the sensitivity of bone marrow aspirates was 40.2%, 65.5%, 89.7%, 92%, and 95.4% at 1, 5, 20, 30, and 60 minutes, respectively. The sensitivity of spleen aspirate examination was 93% for 114 patients. One patient died of shock after spleen aspiration. A bone marrow smear is very sensitive if examined thoroughly, reaching a sensitivity similar to that of spleen aspirate. We propose that a bone marrow smear be established as the technique of choice for the parasitologic diagnosis of VL.

Adolescent↗
PubMed2004

The effect of cataract surgery on ocular levels of topical moxifloxacin.

PURPOSE: To investigate the effect of cataract surgery on the concentration of moxifloxacin in aqueous and vitreous humor after topical application. DESIGN: Prospective laboratory intervention using a rabbit model. METHODS: Following topical administration of 0.5% moxifloxacin, 60 minutes before surgery and immediately post cataract surgery, aqueous and vitreous humor were sampled at 30, 60, and 120 minutes postsurgery. Moxifloxacin concentrations were determined by high-pressure liquid chromatography (HPLC). Mean tissue concentrations obtained in surgical eyes were compared with concentrations obtained in nonsurgical eyes. The potential effectiveness of moxifloxacin in providing prophylaxis against intracameral bacterial inoculation was investigated by comparing antibiotic concentrations to minimum inhibitory concentration (median MIC90) values for Staphylococcus aureus and Staphylococcus epidermidis. RESULTS: In surgical eyes, mean moxifloxacin concentrations in aqueous were 13.9, 16.2, and 12.2 microg/ml versus 25.3, 32.6, and 15.7 microg/ml in nonoperated eyes at 30, 60, and 120 minutes, respectively. No statistically significant differences were found between surgical and nonsurgical eyes. In surgical eyes, mean moxifloxacin concentrations in vitreous were 66.8, 66.6, and 400.2 ng/ml versus 43.1, 199.8, and 54.4 ng/ml in nonoperated eyes at 30, 60, and 120 minutes, respectively. These differences were not statistically significant. CONCLUSIONS: There were no statistically significant differences in the penetration of topical moxifloxacin in eyes undergoing cataract surgery compared with unoperated eyes. A multiple-drop schedule of moxifloxacin produced aqueous concentrations that were well above the MICs of even resistant strains of the most common organisms implicated in postcataract surgery endophthalmitis.

Administration, Topical↗
PubMed2003

Predictors of an unsatisfactory response to pentavalent antimony in the treatment of American visceral leishmaniasis.

Although treatment of visceral leishmaniasis with pentavalent antimony is usually successful, some patients require second-line drug therapy, most commonly with amphotericin B. To identify the clinical characteristics that predict an inadequate response to pentavalent antimony, a case-control study was undertaken in Teresina, Piaui, Brazil. Over a two-year period, there were 19 cases of VL in which the staff physicians of a hospital prescribed second-line therapy with amphotericin B after determining that treatment with pentavalent antimony had failed. The control group consisted of 97 patients that were successfully treated with pentavalent antimony. A chart review using univariate and multivariate analysis was performed. The cure rate was 90% with amphotericin B. The odds ratio for the prescription of amphotericin B was 10.2 for children less than one year old, compared with individuals aged over 10 years. Patients who presented coinfection had an OR of 7.1 while those on antibiotics had an OR of 2.8. These data support either undertaking a longer course of therapy with pentavalent antimony for children or using amphotericin B as a first-line agent for children and individuals with coinfections. It also suggests that chemoprophylaxis directed toward bacterial coinfection in small children with VL may be indicated.

Adolescent↗
PubMed2003

Infection after blepharoplasty with and without carbon dioxide laser resurfacing.

PURPOSE: To determine the rate of infection in patients who underwent blepharoplasty with and without carbon dioxide laser resurfacing. DESIGN: A retrospective, nonrandomized, consecutive case series. PARTICIPANTS: Eighteen hundred sixty-one patients who underwent upper or lower blepharoplasty, with or without carbon dioxide laser resurfacing. METHODS: Charts of patients who underwent blepharoplasty, with or without laser resurfacing, were analyzed for the presence of postoperative infection, method of treatment, and possible sequelae. MAIN OUTCOME MEASURES: The rate of infection (%) was determined for each group of patients. RESULTS: Infection occurred in 0.2% of patients who underwent blepharoplasty without laser resurfacing and 0.4% of patients who had adjunctive laser resurfacing. No permanent functional or cosmetic sequelae resulted from the episodes of infection. CONCLUSIONS: Infection after blepharoplasty without laser resurfacing is uncommon, indicating that topical antibiotic ointment prophylaxis is a sufficient postoperative regimen. The use of adjunctive laser resurfacing may increase the infection rate slightly.

Blepharoplasty↗
PubMed2002

Amniotic membrane graft in the surgical management of cryptophthalmos.

PURPOSE: To describe a case of cryptophthalmos in which an amniotic membrane graft was used in reconstruction of the upper eyelid and fornix. METHODS: The surgical history of a patient with partial cryptophthalmos is presented. RESULTS: Successful creation of a superior fornix in a case of partial cryptophthalmos was achieved only after an amniotic membrane graft was used. CONCLUSIONS: Amniotic membrane is a useful resource for fornix reconstruction in cryptophthalmos.

Amnion↗