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Biomedical subjects

C S Foster

Publications and source records attributed to C S Foster.

At least 253 records · Page 14Linked to original sources

Scleritis associated with rheumatoid arthritis and with other systemic immune-mediated diseases.

PURPOSE: Rheumatoid arthritis is the most common systemic immune-mediated condition associated with scleritis. The purpose of this study is to determine whether or not scleritis is more severe in patients with rheumatoid arthritis than in those without associated disease ("idiopathic scleritis"), or than in patients with other systemic immune-mediated diseases. METHODS: Patient characteristics, type of scleritis, and ocular complications of 32 patients with scleritis associated with rheumatoid arthritis were compared with those of 74 patients with idiopathic scleritis and with those of 50 patients with scleritis associated with other systemic immune-mediated diseases. RESULTS: Patients with scleritis associated with rheumatoid arthritis were older (mean age, 60.78; P = 0.0011) and more often had necrotizing scleritis (34%; P = 0.0001), decrease in vision (59%; P = 0.0001), and peripheral ulcerative keratitis (31%; P = 0.0001) than patients with idiopathic scleritis; by contrast, there was no statistical association with sex, bilaterality, anterior uveitis, glaucoma, or cataract. Patients with scleritis associated with rheumatoid arthritis were older (P = 0.0261) and more often had bilateral scleritis (53%; P = 0.0221) than patients with scleritis associated with other systemic immune-mediated diseases; however, there was no statistical association with type of scleritis, sex, decrease in vision, anterior uveitis, peripheral ulcerative keratitis, glaucoma, or cataract. CONCLUSIONS: Scleritis associated with rheumatoid arthritis is more severe than idiopathic scleritis but is as severe as scleritis associated with other immune-mediated diseases.

Adolescent↗

Differential expression of alternatively spliced fibronectin in normal and wounded rat corneal stroma versus epithelium.

PURPOSE: The polymerase chain reaction was used to examine fibronectin (FN) expression during corneal scrape wounding with specific attention to the presence, absence, or gross changes of alternatively spliced FN as differentially expressed in the corneal stroma versus the epithelium in normal and wounded tissue. METHODS: Specific FN cDNA sequences were synthesized from rat cornea with total RNA and were amplified using various sets of synthetic oligonucleotide primers. RESULTS: The authors observed the presence and sustained the expression of total FN, EIIIA, EIIIB, and V-region FN mRNA in normal and injured corneal stroma for up to 3 weeks after scrape wounding. In contrast, complementary overlying epithelial samples were virtually devoid of FN message. CONCLUSIONS: These data suggest that functionally different, alternatively spliced FN isoforms may be involved both in the maintenance of the normal cornea and in wound healing, and that their synthesis occurs in situ principally by the stroma rather than by the epithelium.

Alternative Splicing↗

Heat shock protein expression in human conjunctiva.

PURPOSE: To examine the distribution of human heat shock proteins (HSPs) HSP90, inducible HSP70 (iHSP70), constitutive and inducible HSP70 (cHSP70), HSP65, and human HSP27 in conjunctival biopsy specimens of ocular cicatricial pemphigoid (OCP), atopic keratoconjunctivitis, and healthy persons with cataract. METHODS: Using an immunoperoxidase technique, conjunctival biopsy specimens from ten patients with ocular cicatricial pemphigoid, ten patients with atopic keratoconjunctivitis and ten healthy persons undergoing cataract surgery were analyzed with a panel of monoclonal antibodies directed against human HSPs. RESULTS: Large amounts of HSP90 and HSP27, and lesser amounts of cHSP70, iHSP70, and HSP65 were present in atopic keratoconjunctivitis and normal epithelium; less of these proteins were seen in OCP conjunctival epithelium. In atopic keratoconjunctivitis and normal tissue the substantia propria contained a few HSP-positive cells, and the vascular endothelium was consistently negative for all of the HSPs. In sharp contrast, OCP stroma contained large numbers of cells staining for HSP27, HSP90, and iHSP70, and the vasculature was strongly positive, particularly for HSP90, cHSP70, and HSP27. CONCLUSION: These results indicate that normal and atopic keratoconjunctivitis epithelia express HSP90 and HSP27 and some form of HSP65 and HSP70. The differences between normal, atopic keratoconjunctivitis, and OCP stromal staining suggest an upregulated expression of HSP90, cHSP70, and HSP27 at the site of inflammation in OCP, the stroma, from cytokine release. The striking presence of HSP in the conjunctival vascular endothelium from OCP patients suggests a previously unappreciated role of the vasculature in OCP.

Aged↗

A 31P and 1H-NMR investigation in vitro of normal and abnormal human liver.

Spectral changes in human hepatic tumours and possible systemic effects of tumour on host liver were assessed by 31P and 1H in vitro NMR spectroscopy. The 1H and 31P spectra from liver tumour biopsies showed significant elevation in phosphoethanolamine, phosphocholine, taurine, citrate, alanine, lactate and glycine, and significant reduction in GPE (glycerophosphoethanolamine), GPC (glycerophosphocholine), creatine and threonine compared to histologically normal tissue. 31P-NMR spectra obtained from histologically normal tissue within tumour-bearing livers showed significant elevation in phosphoethanolamine and phosphocholine compared to data from liver biopsies from nontumour-bearing patients (pancreatitis). These results suggest that alterations in membrane metabolism in host liver can be detected by 31P-NMR.

Biopsy↗

Exacerbation of murine herpes simplex virus-mediated stromal keratitis by Th2 type T cells.

Corneal infection of susceptible mice with HSV-1 causes herpetic stromal keratitis (HSK), which serves as a model of human HSK. To study the properties of the T lymphocytes involved in HSK, susceptible mice were immunized with the synthetic peptide corresponding to the amino terminal of HSV-1-associated glycoprotein D (gD 5-23). A CD4+ long-term T cell line and a clone bearing V beta 8.2 TCR were derived from peptide-primed lymph node cells. These T cells recognize gD 5-23 peptide in the context of I-Ed and require CD4 and LFA-1 for Ag-specific proliferation. Significantly, a truncated peptide gD 15-23 induced vigorous proliferation, indicating that these 9 amino acids constitute an epitope recognized by these T cells. The gD-specific T cells produced IL-4 and used it as the autocrine growth factor and hence belong to the Th2 subtype. Adoptive transfer of gD-specific Th2 cells into susceptible mice increased both the onset and severity of HSK after corneal HSV-1 infection. Injection of gD-specific Th2 cells without HSV-1 infection failed to cause eye damage. In addition, an irrelevant Ag-specific Th2 clone failed to induce similar tissue damage when the corresponding Ag was applied to the eye. These data indicate that the T cell-mediated exacerbation of HSK in these studies is dependent on the specific recognition of gD after corneal HSV-1 infection. Finally, gD-specific Th2 cell transfer also rendered HSK-resistant mice susceptible for HSK, suggesting that the freedom from HSK in resistant mice may primarily be due to their inability to produce the pathogenic Th2 cells. The data collectively implicate an important role for Th2 cells in the induction of HSV-mediated keratitis in mice.

Amino Acid Sequence↗

Immunohistopathologic features and therapy of conjunctival lichen planus.

Lichen planus is an autoimmune disease that typically involves skin and the mucosa of the genitalia and mouth. Conjunctival involvement is rare, and the microscopic abnormalities of affected conjunctivae are not well characterized. We treated two patients with cicatrizing conjunctivitis and extraocular conjunctival lichen planus confirmed by biopsy. We found irregular, thickened basement membrane with reduplications similar to the findings in oral mucosa affected by lichen planus. The absence of basement membrane immunoreactants excluded ocular cicatricial pemphigoid. Results of laboratory tests for collagen vascular diseases including sarcoidosis and lupus were also negative. Treatment with 2% cyclosporine eyedrops controlled inflammation and stopped cicatrization in one patient who was followed up for 12 months. The other patient, in whom lichen planus was recently diagnosed, responded favorably to topical cyclosporine. Lichen planus should be included in the differential diagnosis of cicatrizing conjunctivitis and its immunohistopathologic features should be studied in conjunctival biopsies. Topical cyclosporine may be used successfully for conjunctival lichen planus.

Adult↗

Peripseudophakic membrane. Pathologic features.

A 70-yr-old woman underwent anterior segment reconstruction with repeated penetrating keratoplasty for visual rehabilitation. On removal of the failed keratoplasty button, the posterior chamber intraocular lens was found to be encased in a dense fibrous membrane that almost totally obliterated the anterior and posterior chambers of the eye. Anterior segment reconstruction included excision of the fibrous membrane, removal of the intraocular lens, iridoplasty, gonioplasty, anterior vitrectomy, and repeated penetrating keratoplasty. Recognition of fibrous tissue that extended through each of the four positioning holes of the optic of the lens implant and its transection was essential in avoiding complications during removal of the intraocular lens. Histopathologic and ultrastructural examination of the excised membrane revealed areas of metaplastic lens epithelium and fibrous scar tissue. This study, using immunofluorescence, is the first, to our knowledge, to characterize the specific collagenous components of a peripseudophakic membrane.

Aged↗

Multidrug resistance and behavioural phenotype of cancer cells.

Resistance to cytotoxic chemotherapy is a major obstacle preventing successful treatment of cancer, allowing dissemination of tumour metastases, and may be viewed as the ultimate cause of death in the majority of patients with a malignant disease. Although cytotoxic chemotherapy is classically employed to produce maximal killing of malignant cells, the therapeutic doses of individual drugs required to achieve this objective are, in general, highly toxic to non-neoplastic host tissues. However, there are several different aspects of cancer cell biology, distinct from their susceptibility to cytotoxicity, that might be exploited in order to alter the behavioral phenotypes of malignant neoplasms. Such features include regulation of cell proliferation, tumorigenicity and metastatic potential. Non-cytotoxic modulation of malignant cells may provide an alternative, and more effective, method of controlling the aggressive behaviour of cancer cells while exhibiting less iatrogenic morbidity and mortality than the therapeutic regimens presently employed.

Animals↗

Infectious scleritis: report of four cases.

While systemic autoimmune diseases are the main possibilities in the differential diagnosis of scleritis, other less common etiologies such as infections must also be considered. The authors report four cases of infectious scleritis to review predisposing factors, clinical characteristics, methods of diagnostic approach, and response to therapy. Two patients had primary scleritis and two patients had secondary scleritis following extension of primary corneal infection (corneoscleritis). Diagnoses included three local infections (one each with Staphylococcus. Acanthamoeba, and herpes simplex) and one systemic infection (Lyme disease). Stains, cultures, or immunologic studies from scleral, conjunctival, and/or corneal tissues, and serologic tests were used to make the diagnosis. Medical therapy, including antimicrobial agents, was instituted in all patients, and surgical procedures were additionally required in two patients (scleral grafting in one and two penetrating keratoplasties in another); the patient who required two penetrating keratoplasties had corneoscleritis and underwent eventual enucleation. Infectious agents should be considered in the differential diagnosis of scleritis.

Amebiasis↗

Systemic (serum) soluble interleukin-2 receptor levels in corneal transplant recipients.

Elevated soluble interleukin-2 receptor levels (sIL-2R), a measure of T cell activation, have been used as a serum marker for early rejection in solid organ transplant patients. In this preliminary study, we measured sequential sIL-2R levels of 53 otherwise immunologically normal corneal transplant recipients. Eleven of these transplants rejected; sIL-2R was significantly elevated during the acute rejection episode, compared to pre-rejection and post-rejection levels (p = 0.01). Five patients' sIL-2R rose one to nine months prior to rejection. These data indicate that sIL-2R levels may correlate with corneal graft rejection and may be predictive of impending rejection. A larger prospective study with many immunologically normal patients and careful monitoring of sIL-2R levels prior to and during the acute rejection episode will be necessary to determine the value of sIL-2R monitoring as a predictive tool for corneal graft rejection.

Acute Disease↗

Ocular presentation of polyarteritis nodosa. Clinical course and management with steroid and cytotoxic therapy.

BACKGROUND: Polyarteritis nodosa is a necrotizing vasculitis affecting medium and small-sized arteries throughout the body, including ocular tissues. Untreated polyarteritis nodosa carries a very poor prognosis. Treatment with steroids increases the 5-year survival to 48%, whereas addition of cytotoxic immunosuppressive treatment improves the outcome dramatically. METHODS: The authors reviewed five cases of polyarteritis nodosa with a spectrum of ocular findings which preceded and contributed to its diagnosis. RESULTS: The ophthalmic manifestations of polyarteritis nodosa in these patients included scleritis, peripheral ulcerative keratitis, nongranulomatous uveitis, retinal vasculitis, pseudotumor of the orbit, and central retinal artery occlusion associated with temporal arteritis. In four patients, cytotoxic immunosuppressive therapy was begun promptly, and elimination of inflammation was achieved. CONCLUSIONS: The authors' presentation of these cases is intended to emphasize the fact that ocular inflammation can be the earliest presenting manifestation of polyarteritis nodosa and that its recognition may lead to the early institution of therapy, which can decrease morbidity and mortality in this disease.

Adult↗

An analysis of therapeutic decision for scleritis.

PURPOSE: To compare the long-term efficacy of different systemic therapeutic regimens for patients with noninfectious anterior scleritis to establish guidelines for institution of therapy. METHODS: Therapeutic failure of systemic nonsteroidal anti-inflammatory drugs (NSAIDs), systemic steroidal anti-inflammatory drugs, and systemic nonsteroidal immunosuppressive drugs was evaluated in 132 patients with noninfectious anterior scleritis (diffuse, nodular, or necrotizing types). RESULTS: In patients with diffuse scleritis, therapeutic failure for initial regimens occurred in 7% of patients treated with NSAIDs, in 16% of patients treated with steroids, and in 27% of patients treated with immunosuppressive drugs. In patients with nodular scleritis, therapeutic failure for initial regimens occurred in 9% of patients treated with NSAIDs, in 28% of patients treated with steroids, and in 25% of patients treated with immunosuppressive drugs. Addition or substitution of steroids or immunosuppressive drugs as second- or third-line therapies helped control the scleritis. In patients with necrotizing scleritis, therapeutic failure for initial regimens occurred in 100% of patients treated with NSAIDs, in 91% of patients treated with steroids, and in 26% of patients treated with immunosuppressive drugs. CONCLUSIONS: In patients with diffuse and nodular scleritis, NSAIDs should be the initial choice; in case of therapeutic failure, steroids should be added or substituted as second-line therapy, tapering and discontinuing them as soon as possible while maintaining remission with continued NSAIDs; in case of therapeutic failure, immunosuppressive drugs should be added or substituted as third-line therapy. In patients with necrotizing scleritis, immunosuppressive drugs should be the initial choice.

Adolescent↗

Atypical ocular atopy.

BACKGROUND: Atopic keratoconjunctivitis (AKC) is defined as a chronic keratoconjunctivitis associated with atopic dermatitis, but severe progressive keratoconjunctivitis as a sole manifestation of atopy also may occur. The authors report three patients with a longstanding history of chronic conjunctivitis with bilateral pannus formation. These patients denied any history of major atopy at the time of presentation. METHODS: All patients were evaluated for collagen vascular disease and for evidence of atopy. Conjunctival biopsy was obtained in each case and was analyzed by light microscopy and by immunohistochemical techniques. RESULTS: Systemic evaluation for collagen vascular disease was negative. Serum IgE levels were elevated in one patient. Conjunctival biopsy suggested atopy in all patients with characteristic histopathologic findings. Referral to an allergist showed wheal and flare reactions to multiple ubiquitous environmental allergens. Two patients then disclosed a history of atopic dermatitis and another confessed a history of asthma. Each patient responded well to environmental control of allergens, topical cromolyn sodium 4%, and systemic antihistamine therapy with subsequent resolution of the chronic conjunctivitis. The corneal complications were managed with pannus resection and postoperative mitomycin C drops in two patients. CONCLUSION: These patients suffered from the progressive blinding consequences of a chronic keratoconjunctivitis, which we believe is an atypical form of AKC. In this report, it is suggested that atopy should be considered in some cases of external ocular inflammation, even in the absence of the characteristic findings of systemic atopy. Conjunctival biopsy is a valuable diagnostic tool in such cases.

Adult↗

Long-term results of mucous membrane grafting in ocular cicatricial pemphigoid. Implications for patient selection and surgical considerations.

BACKGROUND: Buccal mucous membrane grafting was performed in 26 eyes of 20 patients with advanced ocular cicatricial pemphigoid. The disease causes abnormalities of the eyelid margin and conjunctiva, which results in mechanical damage to the cornea. The authors' short-term results showed that mucous membrane grafting was effective in reversing these abnormalities if the disease was first medically controlled by chemotherapy or was in remission. METHODS: At the end of 2 years of follow-up, the authors reviewed all records and photographs of these patients. RESULTS: Serious postoperative corneal complications developed in 16 eyes (61.5%), causing worsened visual acuity in 8. The postoperative complications were associated with severe keratoconjunctivitis sicca in 14 eyes (87.5%), progression of subepithelial conjunctival fibrosis and postoperative exacerbation of ocular cicatricial pemphigoid inflammatory activity in 8 eyes, and advanced ankyloblepharon in 7 eyes. The condition of one eye was unchanged. The beneficial effect of grafting was maintained in nine eyes. CONCLUSIONS: The authors' observations indicate that mucous membrane grafting should not be performed when patients have severe keratoconjunctivitis sicca, very advanced ocular cicatricial pemphigoid, or active conjunctival inflammation uncontrolled by immunosuppression. The authors suggest complete control of inflammation before surgery and perioperative treatment with systemic prednisone while maintaining any ongoing immunosuppressive chemotherapy. The selection of alternative surgical approaches is discussed.

Aged↗

Cataract extraction in patients with pars planitis.

BACKGROUND: The authors analyzed the results of cataract surgery performed on patients with pars planitis from January 1985 through August 1992. METHODS: One hundred twenty-six patients with pars planitis were evaluated and treated during this period. Cataracts that warranted surgery developed in 12 patients (18 eyes) from this tertiary referral population. These 12 patients were evaluated with respect to pars planitis duration, systemic disease association, treatment regimens, macular and disc pathology, and final visual result. RESULTS: The average final visual acuity of these 18 eyes was 20/38, and 83% of the patients achieved a final visual acuity better than or equal to 20/40. The factors that limited visual recovery to this level were primarily macular and optic nerve pathology (cystoid macular edema [CME], macular epiretinal membrane, and optic atrophy). Control of inflammation required regional steroids in all patients, systemic steroids in ten patients, and immunosuppression in four patients. Posterior chamber lens implantation accompanied the surgery in 14 eyes (10 patients). Recurrent episodes of inflammation in two patients (3 eyes) resulted in accumulation of deposits on the posterior chamber intraocular lens (IOL) surface. Deposits were removed by a YAG laser lens "polishing" session. CONCLUSION: Absolute control of inflammation in patients with pars planitis through a stepladder approach may reduce the incidence of cataract development, and can certainly improve visual rehabilitation after cataract extraction. Implantation of a posterior chamber lens can be well tolerated in selected cases.

Adult↗

Cataract development and cataract surgery in patients with juvenile rheumatoid arthritis-associated iridocyclitis.

PURPOSE: The authors used an aggressive stepladder, steroid-sparing, therapeutic algorithm in the care of patients with iridocyclitis associated with juvenile rheumatoid arthritis (JRA) to preserve vision, limit cataract formation, and improve probability of successful visual rehabilitation when cataract surgery became necessary. METHODS: The authors treated 60 patients with JRA-associated iridocyclitis with topical and regional corticosteroids, systemic nonsteroidal anti-inflammatory drugs, systemic steroids, and systemic immunosuppressive chemotherapy to achieve total quiescence of intraocular inflammation. Cataract surgery (phacoemulsification extracapsular cataract extraction) combined with pars plana vitrectomy was performed on those eyes with cataract sufficient to limit visual acuity to 20/200 or less, after maintenance of complete freedom from inflammation for at least 3 months. The incidence of cataract development and the visual outcome of cataract surgery were analyzed in those patients for whom a minimum follow-up of 1 year was available. RESULTS: Eventually, 10 of the 60 patients required systemic immunosuppressive chemotherapy in the stepladder therapeutic approach to achieve complete abolition of all active inflammation. Of 72 phakic eyes without cataract, significant cataract developed in 13 (18%) while under our care. The average postoperative stable visual acuity in this group was 20/40. Sixteen eyes of 12 additional patients had visually significant cataract at the time of our first evaluation of them. The average postoperative stable visual acuity in this group of patients after cataract surgery was 20/40. CONCLUSIONS: Iridocyclitis associated with JRA is an insidiously blinding disease, with 12% of individuals affected by this problem eventually blinded by the inflammatory consequences to the eye. A therapeutic philosophy of complete intolerance for active inflammation and limited tolerance for chronic steroid use may offer the most realistic hope for the next step in progress to prevent blindness in this patient population. The results of this study suggest that such a therapeutic attitude results in diminished cataract prevalence and decreased prevalence of vision-limiting retinal pathology, with resultant improved visual outcome of the cataract surgery which is eventually needed in a small proportion of the patients.

Adolescent↗

Altered phosphorylation status, phospholipid metabolism and gluconeogenesis in the host liver of rats with prostate cancer: a 31P magnetic resonance spectroscopy study.

31P magnetic resonance spectroscopy (MRS) in vivo and in vitro was used to study modulation of host liver (HL) metabolism in rats bearing the MAT-LyLu variant of the Dunning prostate tumour. Animals were inoculated either with 10(6) or 10(7) MAT-LyLu cells, or with saline to serve as controls. Carcass weight in tumour-bearing (TB) animals decreased despite similar food and water intake in both groups. Absence of metastatic tumour cells from HL of all TB animals was confirmed by histological examination. Twenty-one days after inoculation, 31P MRS showed a 2.5-fold increase in [Pi]/[ATP] ratios in HL in vivo (P < 0.001) which was confirmed by 31P MRS of liver extracts in vitro (P < 0.005). Phosphodiester to ATP ratios were significantly increased (P < 0.05) in HL in vivo, but absolute PDE levels were similar in both groups. Phosphomonoester to ATP ratios did not change, although absolute phosphomonoester levels in HL were reduced by -41% (not significant). In HL extracts in vitro, sharp reductions in the levels of glucose-6-phosphate (P < 0.05), fructose-6-phosphate (P = 0.05), phosphocholine (P < 0.001), glycerophosphocholine (P < 0.001), and glycerophosphoethanolamine (P < 0.001) were observed. Electron microscopy revealed increased amounts and altered distribution of rough endoplasmic reticulum in HL. These findings show that experimental prostate cancer significantly affects hepatic phosphorylation status, phospholipid metabolism, and gluconeogenesis in the host animal, and demonstrate the value of combined MRS in vivo and in vitro in monitoring HL metabolism in cancer.

Animals↗