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Biomedical subjects

C S Foster

Publications and source records attributed to C S Foster.

At least 109 records · Page 6Linked to original sources

Medical treatment of macular edema in patients with uveitis.

PURPOSE: To determine the efficacy of medical treatment of cystoid macular edema (CME) in patients with uveitis. METHODS: Retrospective study of 40 patients (57 eyes) with uveitis and CME. Inclusion criteria were presence of CME with minimal and no macular pathology, or vascular disease which could account for CME. Patients who had undergone intraocular surgery or had visual acuity (VA) of > or = 20/40 were excluded. The diagnosis of CME was based on clinical and/or angiographic findings. Three treatment groups were defined: (1) transseptal injection of steroids (n=13 eyes); (2) systemic non steroidal anti-inflammatory drugs (NSAIDs) (n=11 eyes); both 1 and 2 (n=33 eyes). RESULTS: Overall, 79% of eyes improved 3 or more lines of Snellen VA after treatment: 51% improved 4 or more lines. The average number of lines improved was 3.8 for eyes treated with transseptal injections of steroids, 2.9 for eyes treated with NSAIDs, and 4 for eyes treated with both. For all 3 treatment groups between 60-70% of eyes improving 2 or more lines reached best VA only after a minimum of 6 months of follow up. CONCLUSIONS: CME, a vision threatening complication of uveitis, respond fairly well to medical treatment; however, the best VA is achieved after several months. The improvement in VA did not differ markedly among the three treatment groups.

Adolescent↗

Cytokine mRNA in BALB/c mouse corneas infected with herpes simplex virus.

PURPOSE: To investigate cytokine mRNA expression and the influence of acyclovir and tetrandrine on that expression in the corneas of mice infected with herpes simplex virus type 1 (HSV-1). METHODS: Male BALB/c mice were infected in the right cornea with HSV-1. The corneas were harvested from control normal mice and from untreated, acyclovir-treated and tetrandrine-treated mice 14 days after infection. The infected corneas of each group were divided into inflamed and uninflamed depending on clinical observation. After total mRNA extraction from the corneas, gene expression of interleukin 1 beta (IL-1 beta), IL-6, tumour necrosis factor alpha (TNF-alpha) and transforming growth factor (beta (TGF-beta) was analysed by reverse transcription polymerase chain reaction. RESULTS: No mRNA expression of the cytokines was found in normal corneas. IL-1 beta and TNF-alpha mRNA was seen in inflamed corneas, while mRNA expression of IL-6 and relatively weaker TGF-beta mRNA expression were found both in inflamed corneas and in infected but uninflamed corneas treated with acyclovir. TNF-alpha mRNA was present in the uninflamed corneas of tetrandrine-treated mice. No influence of either agent was found on TGF-beta gene expression. CONCLUSIONS: The results suggest that local IL-1 beta and TNF-alpha gene expression is required for corneal inflammation, whereas IL-6 and TGF-beta may exert antiviral and inflammation regulatory activities in HSV corneal infection.

Acyclovir↗

Ocular surface neoplasia masquerading as chronic blepharoconjunctivitis.

PURPOSE: To present the clinical characteristics and difficulties in the diagnosis of various ocular surface malignancies mimicking features of chronic blepharoconjunctivitis and to summarize the current therapeutic approach and prognosis of patients. METHODS: Six patients with slowly evolving signs of persistent inflammation underwent a conjunctival biopsy after a prolonged course of medical treatment. The medical records of the patients were reviewed. RESULTS: Histopathologic examination of the biopsy specimens revealed intraepithelial squamous neoplasia (one patient), invasive squamous cell carcinoma (one patient), sebaceous carcinoma (two patients), and conjunctival lymphoma (two patients). CONCLUSION: Although uncommon, ocular surface malignancies may involve the conjunctiva diffusely and present as chronic conjunctivitis. A high index of suspicion and an early histopathologic examination are essential to not delay diagnosis.

Adenocarcinoma, Sebaceous↗

Krill protease effects on wound healing after corneal alkali burn.

PURPOSE: To study the effect of a novel protease in the development and progression of corneal ulceration secondary to alkali burning. METHODS: By using a 4N alkali burn model of corneal ulceration in rabbits, the effects and efficacy of topical application of a novel protease (PHM-101) capable of degrading metalloproteinases was studied for 28 days of treatment and 7 days off treatment for its effect on corneal ulceration and recurrent erosion. RESULTS: At day 28, both the protease- and placebo-treated groups had different numbers of eyes showing reepithelialization (nine (45%) of 20 and six (33%) of 18, respectively]. By day 35 the protease-treated group had significantly fewer recurrent epithelial defects [two (13%) of 15 vs. eight (61%) of 13; p = 0.02]. Similarly, at day 35 the protease-treated group showed significantly less corneal ulceration [two (13%) of 15 vs. six (46%) of 13; p = 0.02], and those ulcers were of a lesser severity (three units vs. 17.76 units). No difference was found in the degree of stromal edema or neovascularization, nor was there any difference in histopathologic characteristics of inflammatory cell infiltration and corneal scarring. CONCLUSION: We conclude that this novel protease is efficient in reducing recurrent corneal epithelial defects and stromal ulceration after alkali burning.

Alkalies↗

Scleral patch graft in the management of necrotizing scleritis.

NS is a rare but devastating consequence of certain connective tissue disorders, most commonly RA. The presence of NS mandates that patients be treated with at least one immunosuppressive chemotherapeutic drug. The cure rate is high in such instances after 1 year of freedom from any evidence of recurrent inflammation. Surgical treatment through tectonic scleral and peripheral corneal grafting is rarely (although sometimes) indicated, except in instances of NS that has advanced to the point of perforation of the globe. Various graft materials can be used, including fascia lata, periosteum, split-thickness dermis, Gore-Tex (synthetic), aortic tissue, and autologous or homologous sclera. Surgical treatment alone will not solve the problem for the patient. The physician also must control the underlying immunoregulatory dysfunction that has caused the destruction initially to protect the graft and, subsequently, the patient's eye.

Female↗

Diagnostic vitrectomy and uveitis.

When properly used, diagnostic vitrectomy can be an extremely helpful procedure for establishing the etiology of ocular inflammation. New instruments have enabled more expedient and safer surgery. Analytical assays continue to improve in quality and quantity as our understanding of ocular diseases grows. Though no single assay is completely sensitive, a combination of assays may improve the yield and accuracy of diagnostic vitreous biopsy (Table 5). Keeping abreast of these advances may aid ophthalmologists in obtaining earlier diagnosis and better outcomes for their patients.

Biomarkers↗

Secondary glaucoma in patients with uveitis.

PURPOSE: To evaluate the prevalence of secondary glaucoma (SG), clinical forms of uveitis more frequently associated with glaucoma, and describe the treatment and complications encountered in a cohort of patients with glaucoma and uveitis during a 10-year period. METHODS: The hospital records of patients with uveitis referred to the Immunology Service of the Massachusetts Eye and Ear Infirmary for a decade were reviewed for cases of SG. RESULTS: One hundred and twenty of the 1,254 patients (9.6%) with uveitis developed SG. SG was more frequent in anterior uveitis (67%) but was also associated with posterior uveitis (13%) and pars planitis (4%). Herpetic keratouveitis (22%), Fuchs' iridocyclitis (19%), juvenile rheumatoid arthritis-associated iridocyclitis (16%), syphilis (14%), and sarcoidosis (12%) were the leading types of uveitis associated with SG. Despite aggressive medical and surgical therapy, SG was associated with progressive visual field loss and optic nerve damage in 39 patients (33%). CONCLUSION: SG is an underappreciated, vision-threatening complication in patients with uveitis. Increased vigilance for emergence of this complicating problem during the care of patients with uveitis is warranted, and medical and surgical treatment for reducing IOP should be especially aggressive in these patients. We hypothesize that earlier, more aggressive treatment of uveitis will reduce the presence of glaucoma as an additional vision-robbing complication of uveitis.

Adolescent↗

Soluble P-selectin glycoprotein ligand 1 inhibits ocular inflammation in a murine model of allergy.

PURPOSE: To assess the anti-inflammatory modality of a soluble extracellular form of P-selectin glycoprotein ligand 1 (sPSGL-1) in a mouse model of ocular allergic response. METHODS: Potential anti-inflammatory effects of sPSGL-1 were investigated in SWR/J mice sensitized by topical application of short ragweed pollen to the nasal mucosa followed by a challenge of the ocular mucosa with the same allergen. Five experimental groups were included in these studies: A, mice neither sensitized nor challenged with pollen (control group 1); B, animals sensitized but not challenged (control group 2); C, animals not sensitized but challenged (control group 3); D, animals sensitized and challenged; and E, sensitized animals treated with sPSGL-1 before pollen challenge. All experimental groups were evaluated for gross morphologic ocular changes, and histologic assessments were made to determine the onset/progression of inflammatory reactions and to look for evidence of eosinophil infiltration. RESULTS: Mice sensitized and challenged with pollen developed clinical signs consistent with human allergic conjunctivitis. These signs correlate with histologic changes in the conjunctival epithelium and stroma (e.g., edema and extensive eosinophil infiltration). Moreover, the ocular changes also correlated with evidence of eosinophil degranulation. However, sensitized and challenged mice concurrently treated with sPSGL-1 displayed no inflammatory ocular changes associated with a ragweed-induced type-1 hypersensitivity reaction. The lack of ocular changes included the absence of histologic late-phase inflammatory changes of the conjunctiva and a 97% reduction in the induced eosinophil infiltrate. CONCLUSIONS: The antagonistic intervention of cell- cell interactions through the blockade of selectin-dependent leukocyte adhesion may offer novel therapeutic strategies to modulate inflammatory responses. The potent inhibitory effects on eosinophil recruitment and late-phase inflammation suggest a role for sPSGL-1 in the treatment of ocular allergic diseases.

Animals↗

The role of antibody to human beta4 integrin in conjunctival basement membrane separation: possible in vitro model for ocular cicatricial pemphigoid.

PURPOSE: To demonstrate the specific binding of autoantibodies present in the sera of patients with ocular cicatricial pemphigoid (OCP) to human beta4 integrin present in the normal human conjunctiva (NHC) and to study the role of OCP autoantibodies and antibody to human beta4 integrin in the pathogenesis of subepithelial lesion formation in OCP. METHODS: Indirect immunofluorescence assay and in vitro organ culture method using NHC were used. Sera and IgG fractions from 10 patients with OCP; immunoaffinity-purified OCP autoantibody; antibodies to human beta4, beta1, alpha6, and alpha5 integrins; and sera from patients with pemphigus vulgaris, bullous pemphigoid (BP), and chronic atopic and chronic ocular rosacea cicatrizing conjunctivitis; and normal human serum (NHS) were used. RESULTS: Nine of 10 OCP sera or IgG fractions, immunoaffinity-purified OCP autoantibody, antibodies to human beta4 and alpha6 integrins, and sera from patients with BP showed homogenous, smooth linear binding along the basement membrane zone (BMZ) of the NHC. NHS, antibodies to other integrins, and sera from patients with chronic cicatrizing conjunctivitis from other causes showed no such binding. When NHC was first absorbed with OCP sera and then reacted with anti-beta4 antibodies or vice versa, the intensity of the BMZ binding was dramatically reduced or completely eliminated, indicating that there were autoantibodies in OCP sera specific for the beta4 integrin. BMZ separation developed 48 to 72 hours after addition of total OCP sera, IgG fractions from OCP sera, immunoaffinity-purified autoantibodies from sera of patients with OCP, or anti-beta4 antibodies to the NHC cultures, but not after addition of normal control sera, sera from patients with chronic cicatrizing conjunctivitis from causes other than OCP, or sera from patients with OCP in clinical remission. CONCLUSION: Circulating anti-beta4 integrin antibody may have an important role in the pathogenesis of OCP.

Antigens, CD↗

Predictive factors in prostate cancer: current concepts from the 1999 College of American Pathologists Conference on Solid Tumor Prognostic Factors and the 1999 World Health Organization Second International Consultation on Prostate Cancer.

Many clinically important predictive factors in prostate cancer are derived from light microscopic examination of tissue specimens by the pathologist. Two separate international consensus conferences held in 1999 addressed the contemporary status of such prognostic factors, sponsored by the College of American Pathologists (CAP) and the World Health Organization (WHO). Both conferences concluded that the following factors are recommended for routine use based on evidence from multiple published trials: TNM stage, histological grade using the Gleason system, surgical margin status, and serum prostate-specific antigen concentration. The WHO conference additionally recommended use of WHO nuclear grade, location of cancer within the prostate, and pathological effects of treatment. Other factors were categorized as promising or of unproven utility, including a wide variety of histopathologic and genetic markers. Standards are needed for analysis and quantitation of methods of tissue analysis, particularly for immunohistochemical studies and genotypic studies. This report describes the recommendations and conclusions of these two conferences.

Apoptosis↗

The role of cytokines in experimental herpes simplex keratitis.

Experimental corneal infection with herpes simplex virus 1 (HSV-1) resulted in 11-21 days in herpes simplex keratitis (HSK) in C.A1-20 but not C.B-17 strain of BALB/c Igh-1-disparate mice. Formation of mRNAs of various pro-inflammatory cytokines was analyzed in corneas and draining lymph nodes (LNs) of HSK-susceptible C.A1-20 and HSK-resistant C.B-17 mice following HSV-1 corneal inoculation by reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analysis. Transcripts for interleukin (IL)-2 and interferon (IFN)-gamma were expressed in LNs of susceptible but not resistant mice. The level of IL-6 expression in the cornea correlated with the severity of keratitis in susceptible mice, being evident at days 4 and 14 after virus inoculation and thus showing a biphasic response. Resistant mice did not develop HSK and did not express IL-6. The IL-1beta and IL-4 gene transcription began early (day 7) in the corneas of resistant mice and then ceased, while in the corneas of susceptible mice, it began later (day 11). Taken together, these results indicate that IL-1beta, IL-4, IL-6, and IL-7 participate in the local inflammatory response in HSK.

Animals↗

Sodium channel protein expression enhances the invasiveness of rat and human prostate cancer cells.

Expression of Na+ channel protein was analysed in established cell lines of rat and human prostatic carcinoma origin by flow cytometry using a fluorescein-labelled polyclonal antibody. In many cell lines examined, the obtained frequency distribution profiles were bimodal and identified a subpopulation of cells which expressed high levels of Na+ channel protein. A significant positive correlation was demonstrated between the proportion of channel-expressing cells and the functional ability of individual cell lines to invade a basement membrane matrix in vitro. In addition, two transfectant cell lines containing rat prostate cancer genomic DNA were found to express significantly elevated levels of Na+ channel protein when compared with the original benign recipient cell line. Enhanced Na+ channel expression by two metastatic derivatives of these transfectant cells directly correlated with increased invasiveness in vitro. These studies strongly support the hypothesis that expression of Na+ channel protein and the metastatic behaviour of prostatic carcinoma cells are functionally related, either by endowing the membranes of these cells with specialised electrophysiological properties (e.g. enhancing their motility and/or secretory activities) and/or by perturbing endogenous mechanisms regulating ionic homeostasis within the cells.

Animals↗

Leukocyte adhesion molecule expression in scleritis.

OBJECTIVE: To analyze the expression and cellular distribution of intercellular adhesion molecule 1, E-selectin (endothelial leukocyte adhesion molecule), vascular cell adhesion molecule 1, very late antigen 4, and lymphocyte function associated antigen 1 (LFA-1) in diseased and normal human sclera. METHODS: Monoclonal antibodies to vascular cell adhesion molecule 1, very late antigen 4, intercellular adhesion molecule 1, LFA-1, and E-selectin were used to perform immunohistochemical staining on frozen sections of 16 cryopreserved human sclera specimens and 5 conjunctival specimens. RESULTS: The normal human sclera did not express any of the adhesion molecules. The expression of LFA-1 was dramatic in all the scleral and conjunctival specimens on the inflammatory cells. Intercellular adhesion molecule 1, the ligand for LFA-1, was expressed in 7 of 12 scleral specimens. Furthermore, the expression of LFA-1 and intercellular adhesion molecule 1 were focally present in areas of inflammatory infiltrate. E-selectin expression was detected on the vascular endothelial cells in 8 of 12 patients. There was variable expression of vascular cell adhesion molecule 1 and very late antigen 4 in the inflamed sclera and conjunctiva. CONCLUSIONS: Our results demonstrate the presence of LFA-1 in the sclera and in the conjunctiva of patients with scleritis. Variable expression of other leukocyte adhesion molecules was noted in the sclera and the conjunctiva of these patients.

Antibodies, Monoclonal↗