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Biomedical subjects

C S Foster

Publications and source records attributed to C S Foster.

At least 415 records · Page 23Linked to original sources

Toxicity of intravitreous miconazole.

Miconazole nitrate is a broad-spectrum antimycotic agent with low systemic and ocular toxicity. Since this drug does not adequately penetrate the vitreous cavity by topical, subconjunctival, or intravenous routes, we determined whether it can be given intravitreously for fungal endophthalmitis. Retinal and lens toxicity studies were carried out in 40 rabbits and three owl monkeys. Results showed that both miconazole and its vehicle produced toxic damage to the retina and crystalline lens in concentrations of 100 micrograms or greater. Concentrations of 10 to 80 micrograms caused mild to moderate retinal necrosis in some rabbit eyes. In monkey eyes, these concentrations did not cause significant histopathologic or electroretinographic changes. We believe that clinical use of this drug in doses not to exceed 40 micrograms may be justified in desperate cases of fungal endophthalmitis.

Animals↗

Immunosuppression and selective inflammatory cell depletion. Studies on a guinea pig model of corneal ulceration after ocular alkali burning.

Total ocular-surface alkali burning was performed on guinea pigs to study the effects of generalized immunosuppression and selective inflammatory cell line modifications on corneal ulceration. Central stromal corneal ulceration developed in 86% (18/21) of control eyes three to seven days after alkali burning, whereas ulcers developed in only 16% (3/19) of the eyes of guinea pigs immunosuppressed with cyclophosphamide. Neutrophils, the preponderant inflammatory cells in ulcerating corneas, were conspicuously absent from the nonulcerating corneas. Selective neutrophil suppression by intravenous administration of a highly specific anti-guinea pig neutrophil serum also suppressed the development of corneal ulcerations in this model; in only 25% of the eyes so treated did ulcers develop after alkali burning. T lymphocyte or monocyte modifications with similar monospecific antisera had no effects on the rate of corneal ulceration. Neutrophil depletion after the onset of ulceration halted progression of the corneal ulcer.

Animals↗

Monoclonal antibodies to the human mammary gland. I. Distribution of determinants in non-neoplastic mammary and extra mammary tissues.

Mouse monoclonal antibodies have been raised to the human milk fat globule membrane. The distribution of the antigens detected by four of the antibodies has been examined in formalin-fixed paraffin-embedded human tissues by light microscopic immunocytochemistry. The four antibodies stain lactating breast and normal resting breast. Two exclusively stain the luminal membranes of breast epithelial cells. A third antibody stains in addition the lateral membranes of duct epithelial cells. The fourth antibody stains both epithelial and myoepithelial cells. None of the antibodies is breast specific, nor do they stain every epithelial cell within the breast. Instead, each antibody reveals a complex and heterogeneous distribution of staining throughout the normal tissues. Within the breast, the staining by a given antibody is usually segmental and conforms to secretory units and their associated ducts. Similarly heterogeneous patterns of staining are also observed in the extramammary normal tissues. Despite the apparent morphological identity between breast epithelial cells when examined by conventional light microscopy, the hitherto unrecognised "functional" heterogeneity, which has been revealed by the monoclonal antibodies could have importance in understanding the biology of the normal breast and the pathology of breast cancer.

Antibodies, Monoclonal↗

Monoclonal antibodies to the human mammary gland. II. Distribution of determinants in breast carcinomas.

A range of primary and metastatic human breast carcinomas has been examined with respect to the staining by four monoclonal antibodies which were raised to the human milk fat globule membrane. Within the normal breast the luminal epithelial cells expressing the antigens detected by the monoclonal antibodies were heterogeneous in their distribution. The heterogeneity was not only confined to single cells, but also to regions within the breast. The breast carcinomas also expressed the antigens in a variable manner. Morphological differentiation and functional differentiation, defined by the monoclonal antibodies, were not invariably coincident. Lymph node metastases gave similar results to the primary carcinomas. The monoclonal antibodies have revealed a heterogeneity, with respect to surface antigenic expression, within the normal and neoplastic breast epithelium. This cellular heterogeneity of breast carcinomas, may have significant prognostic and therapeutic implications in the management of primary breast cancer.

Antibodies, Monoclonal↗

T-cell subsets and Langerhans cells in normal and diseased conjunctiva.

To identify the infiltrating mononuclear cells in conjunctival lesions, we stained frozen tissue sections of conjunctiva with a series of monoclonal antibodies against T cells and T-cell subsets with an immunoperoxidase method. In vernal conjunctivitis and ocular pemphigoid, most lymphocytes reacted with the anti-T4 antibodies that define helper/inducer T cells (T4+); a minority reacted with the anti-T8 antibody that defines suppressor/cytotoxic T cells (T8+). However, T8+ cells predominated in a conjunctival specimen from a patient with chronic graft-vs-host disease. A few T8+ cells and rare T4+ cells were also found in normal conjunctiva. In some diseased conjunctivas, there was an increase in cells stained with anti-T6 antibody, which stains Langerhans cells in normal conjunctiva and skin. T lymphocyte subsets and Langerhans cells probably play an important role in the pathogenesis of inflammatory conjunctival lesions.

Antibodies, Monoclonal↗

Immunosuppressive therapy for progressive ocular cicatricial pemphigoid.

In a controlled, nonrandomized, longitudinal cohort study, we studied the efficacy of systemic immunosuppression in treatment of progressive cicatricial pemphigoid affecting the eyes. Twenty-six patients were studied; 18 received systemic immunosuppressive drugs, and eight received conventional therapy. Three patients who received cytotoxic agents withdrew from the study with intolerable gastrointestinal distress. Fourteen of the 15 patients who were immunosuppressed successfully for prolonged periods experienced a cessation of their episodic ocular inflammation and a halting of their progressive conjunctival cicatrization. They maintained vision at least as good as that present when disease activity was brought under control; in two patients vision improved. The one patient who was adequately immunosuppressed and successfully maintained in such a state for two years but who had progressive ocular surface pathology with eventual blindness had concomitant rheumatoid arthritis and severe sicca syndrome. The three patients who withdrew from immunosuppressive therapy and the eight concomitant controls all showed continued episodic conjunctival inflammation and conjunctival cicatrization with development of severe keratopathy and profound visual loss. Complications in this series included alopecia (100%), anemia (78%), gastrointestinal distress (22%), hemorrhagic cystitis (11.1%), and severe leukopenia (5.5%). These results support the notion that abnormal immunoregulatory mechanisms are involved in the progressive disease activity in cicatricial pemphigoid and that systemic immunosuppression may have an appropriate role in the treatment of this disease.

Adult↗

Ocular immune responses. I. Priming of A/J mice in the anterior chamber with azobenzenearsonate-derivatized cells induces second-order-like suppressor T cells.

We studied the cellular immune responses to ocular anterior chamber (AC) priming of mice. A/J mice primed subcutaneously with azobenzenearsonate-coupled spleen cells (ABA-SC) manifested delayed-type hypersensitivity (DTH) in the form of footpad swelling when challenged 5 days later with the diazonium salt of ABA. Mice inoculated with ABA-SC in the anterior chamber at the time of subcutaneous priming, however, were tolerant to ABA. Subconjunctival inoculation with ABA-SC did not tolerize; rather it primed for DTH. Antibodies against ABA were not detectable in significant amounts in mice made tolerant by AC inoculation. The AC-induced tolerance was shown to result from hapten-specific T cell-mediated suppression. Suppressor T cells (Ts) arising from AC priming suppressed the efferent limb of the immune response and did not bear detectable cross-reactive idiotype (CRI) surface receptors. In these phenotypic and functional respects, AC-induced Ts differed from first-order Ts (Ts1) that result from i.v. priming. The results are discussed with respect to immune privilege and the anterior chamber of the eye.

Animals↗

Infectious endophthalmitis. Review of 36 cases.

A three-year retrospective study of 36 cases of infectious endophthalmitis seen at a large referral eye center between 1977 and 1980 was conducted. The criterion for infectious endophthalmitis was the culture of microorganisms from aqueous or vitreous on at least two media. The most frequent pathogen was Staphylococcus epidermis; it was isolated from 18 (50%) of the cases. In cases of infectious endophthalmitis following recent cataract extraction, S. epidermidis was isolated from 10 to 17 eyes (58.8%). Complete loss of visual function occurred in 16 of the 36 eyes (44.4%); a visual acuity of 20/400 or better as recorded in 15 eyes (41.6%) and 20/100 or better in eight (22.2%). Fifty percent of the cases were treated with vitrectomy and intraocular antibiotics. Poor visual outcome was associated with gram-negative organisms or delay of vitrectomy more than 24 hours after the initial diagnosis. In cases of postoperative S. epidermidis endophthalmitis, the most favorable visual outcomes were associated with use of intraocular antibiotics and vitrectomy; 80% of cases so treated had a final visual acuity of 20/400 or better and 60% had a visual acuity of 20/100 or better.

Adult↗

Medroxyprogesterone on corneal ulceration. Its effects after alkali burns on rabbits.

The effect of medroxyprogesterone acetate treatment in preventing or retarding corneal ulceration after alkali burns was studied in rabbits in an attempt to correlate dose and response. The eyes were treated for 21 days with a 0.01% or 1% suspension administered topically four times a day or medroxyprogesterone acetate, 4 mg or 30 mg, given subconjunctivally on alternate days. None of these regimens was noticeably effective, although at times there was a trend toward retarding ulceration. Thus, it was not possible to confirm earlier reports of substantial efficacy of medroxyprogesterone. Corneal stroma with epithelial defects and/or ulcers persistently showed infiltration with neutrophils in the superficial stroma within the epithelial defect, implicating the tears as the source of the inflammatory cells.

Alkalies↗

Ocular toxicity of topical antifungal agents.

We studied, in a rabbit, the ocular toxicity of topical 1% solutions or suspensions of amphotericin B, flucytosine, miconazole nitrate, and ketoconazole. Flucytosine, miconazole, and ketoconazole did not retard the closure of 8.5-mm corneal epithelial defects; amphotericin B greatly retarded the closure of such defects. Amphotericin B produced dramatic pathologic changes in this model; these changes worsened with each day of therapy. Ketoconazole produced modest biomicroscopically and histologically detectable pathologic changes in the regenerating corneal epithelium; flucytosine and miconazole did not produce such changes.

Administration, Topical↗

Miconazole therapy for keratomycosis.

I treated seven patients with keratomycosis (four with Candida infections and three with Aspergillus infections) with topical and subconjunctival miconazole. Progressive corneal ulceration stopped in each case, and clinical evidence of corneal infection disappeared. Posttreatment visual acuities were at least as good as (and usually better than) pretreatment visual acuities. Superficial punctate keratitis was associated with prolonged (one to two weeks) hourly instillation of miconazole, but there was no evidence of serious ocular toxicity.

Adult↗

Penetrating keratoplasty for herpes simplex keratitis.

We conducted a retrospective longitudinal cohort study of 82 penetrating keratoplasties performed to treat herpes simplex keratitis. In 53 cases (65%) there was extensive corneal neovascularization or stromal ulceration and active intraocular inflammation, making the prognosis in these cases poor. Only 32 grafts (39%) were clear at the time of our analysis. Patients with active inflammation, active ulceration, perforation, or extensive neovascularization had particularly poor success rates. Conservative management of perforation before keratoplasty was highly successful (11 clear grafts in 13 eyes [85%]). Other categories with a good prognosis included disciform edema and scarred corneas in quiet eyes. We used a preliminary analysis of the data to build a model to predict the outcome of penetrating keratoplasty in herpes simplex keratitis. The model used preoperative ocular status and management technique as its terms. Testing of the model showed that there were significant differences in outcome between the groups in the sample.

Adult↗