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Biomedical subjects

C S Foster

Publications and source records attributed to C S Foster.

At least 181 records · Page 10Linked to original sources

HLA typing in patients with ocular manifestations of Stevens-Johnson syndrome.

BACKGROUND: Stevens-Johnson syndrome (SJS) is an acute, self-limited, inflammatory disorder of the skin and mucous membranes. With ocular involvement, SJS has been associated with the class I human leukocyte antigen (HLA)-Bw44. This study examined HLA class II associations in patients with SJS with ocular involvement to help identify possible molecular genetic mechanisms underlying disease susceptibility/resistance. METHODS: Twenty-three white patients with ocular complications secondary to SJS had HLA class II typing performed using polymerase chain reaction-based molecular techniques. Genotype frequency was compared with results obtained from 175 control subjects. RESULTS: HLA-DQB1*0601 was present in four (17%) patients with SJS and in five (3%) control subjects (P < 0.05; relative risk = 7.2). There was no association with HLA-DQB1*0301, which previously has been been strongly associated with recurrent erythema multiforme. None of the class II antigens tested appeared to offer a protective effect against the development of disease. CONCLUSION: HLA-DQB1*0601 was found in a significantly disproportionate number of white patients with SJS and ocular complications. The presence of this allele may confer an increased risk for the development of SJS with ocular complications and provides further evidence for an underlying immunogenetic susceptibility to the development of this disease.

Adult↗

Systemic drug toxicity trends in immunosuppressive therapy of immune and inflammatory ocular disease.

PURPOSE: To compare the relative toxicities of six systemic immunosuppressive drugs and systemic corticosteroids used to treat patients with severe ocular inflammatory disease and to identify factors influencing their occurrence. METHODS: The authors reviewed the clinical records of 602 patients with ocular inflammatory disease treated with immunosuppressive drug therapy and/or systemic corticosteroids for adverse systemic effects while undergoing therapy. Proportional hazards regression analysis was performed to identify demographic and clinical factors that influence the occurrence of drug toxicity in these patients. RESULTS: Immunosuppressive drug treatment was more likely to result in discontinuation of therapy because of toxic side effects than was corticosteroid treatment. However, unlike many of the side effects of corticosteroid treatment, the side effects of immunosuppressive therapy were reversible with reduction in dosage or discontinuation of the drug. Gastrointestinal symptoms and hematologic abnormalities accounted for the majority of reported side effects of the immunosuppressive medications. Neuro-psychiatric and endocrine side effects were common in patients taking prednisone. In 17 patients treated with prednisone, pathologic fractures developed, which involved the hips and the spine. Female sex and age older than 60 years also were identified as factors associated with intolerance to drug therapy in the authors' study population. Race and type of systemic ocular disease were not significant factors influencing tolerance to drug therapy. CONCLUSION: These findings suggest that when properly administered and monitored for adverse effects, most immunosuppressive agents used in the current study have similar risk profiles with relatively few serious therapeutic mishaps and largely reversible side effects. In contrast, corticosteroids can result in permanent disabilities as a result of long-term treatment.

Adult↗

Changing patterns in uveitis of childhood.

BACKGROUND: Although uveitis is relatively uncommon in children, its diagnosis and management present a distinct clinical challenge for the physician. An improved knowledge of disease patterns and associated morbidity will help in the care of children with uveitis. METHODS: The authors reviewed the records of 130 patients with onset of uveitis at 16 years of age or younger. The etiology of uveitis, complications encountered, treatment administered, and visual results were analyzed. RESULTS: Uveitis associated with juvenile rheumatoid arthritis (JRA) was the largest group (41.5%) followed by idiopathic uveitis (21.5%) and pars planitis (15.3%). Twenty-six percent of the eyes had less than 20/200 visual acuity at the time of first referral. Patients with JRA had the highest rate of complications: cataract (71%), glaucoma (30%), band keratopathy (66%), and hypotony (19%). The most frequent complication of pars planitis was maculopathy (55%). Final visual acuity was less than 20/200 in 26% of eyes with JRA, 10.5% with pars planitis, and 14% with idiopathic uveitis. CONCLUSION: Uveitis beginning in childhood is a serious disease associated with sight-threatening complications. Juvenile rheumatoid arthritis-associated uveitis remains a leading cause of ocular morbidity in patients with childhood uveitis. Increased awareness by pediatricians, rheumatologists, and ophthalmologists of the seriousness of ocular complications of uveitis in childhood may lead to earlier diagnosis and more effective treatment regimens in the future.

Adolescent↗

Low-dose cyclosporin A therapy in treating chronic, noninfectious uveitis.

PURPOSE: To describe the authors' approach to the management of patients with recalcitrant, chronic, endogenous uveitis using low-dose Cyclosporin A (CSA) alone or in combination with other immunosuppressive agents with attention to the anti-inflammatory efficacy, visual outcome, and side effects of therapy. METHODS: The authors reviewed the records of 50 patients (92 eyes) with uveitis of various etiologies who had been treated with low-dose CSA (2.5-5.0 mg/kg daily) alone or in combination with prednisone and/or azathioprine (1.5-2.0 mg/kg daily). The median follow-up on low-dose CSA was 16 months (range, 6-64 months). RESULTS: Inflammatory control was achieved in 68 (73.9%) eyes, while persistent inflammatory activity was observed in 14 (15.2%). Thirty-eight (41%) eyes improved two Snellen lines or more, 43 (47.0%) stabilized, and 11 (12.0%) lost two lines or more. The CSA was discontinued because of nephrotoxicity in three patients and in each of two with systemic hypertension and constitutional intolerance to the drug, respectively. Thirteen patients enjoy inflammatory remission with this regimen. CONCLUSION: Low-dose CSA used alone or in combination with other immunosuppressive agents is effective in achieving inflammatory control with a favorable visual outcome and provides a useful steroid-sparing strategy in the management of chronic endogenous uveitis. The CSA-associated toxicity may be reduced by initiating therapy at very low initial doses, with incremental dosage escalation to the desired target range.

Adult↗

External beam and intraluminal radiotherapy for locally advanced bile duct cancer: role and tolerability.

BACKGROUND AND PURPOSE: Cholangiocarcinoma is rare but carries a poor prognosis. Radiotherapy has been used either as an adjuvant treatment following surgical resection of tumour or for palliation. The purpose of this study was to assess the feasibility and morbidity of accelerated external beam radiotherapy with or without intraluminal radiotherapy in the treatment of locally advanced bile duct cancer. MATERIALS AND METHODS: Thirty eight patients were treated. Surgical procedures performed prior to radiotherapy were extended hepatectomy (3), hepaticojejunostomy with tumour resection (6), palliative biliary-enteric bypass (6), biopsy (4), Whipple's procedure (1), gastrojejunostomy (1) and cholecystectomy (1). Twenty patients received external beam radiotherapy (ERT). Six patients received one Phase of ERT and 12 received two Phases, separated by a 2-week gap. Dose per Phase was 22.5 Gy in 10 twice daily fractions. After 1989, dose per Phase was increased to 27.5 Gy. One patient received Phase I ERT (30.0 Gy) using conventional fractionation and one patient received an uninterrupted, conventionally fractionate course of treatment (50.0 Gy). Fourteen patients received both ERT and intraluminal radiotherapy (IRT) using iridium-192 (192Ir) wire passed through a percutaneous, transhepatic catheter (median dose, ERT 23.8 Gy + IRT 40.0 Gy). In addition, four patients received IRT alone (median dose 45.0 Gy at 1 cm radius). Patients were followed for at least 42 months. RESULTS: Median overall survival was 15 months. Overall survival for the whole group at 1,2 and 3 years was 59.6%, 32.5% and 16.2%. Thirty four patients died of disease. Radiotherapy caused acute toxicity in seven patients. According to RTOG/EORTC criteria toxicity was Grade 1 in four cases, Grade 2 in two cases and Grade 3 in one case. Two patients developed gastrointestinal bleeding as a late complication of radiotherapy. CONCLUSIONS: Accelerated external beam radiotherapy with or without intraluminal radiotherapy is feasible and associated with acceptable toxicity when used in the management of advance cholangiocarcinoma.

Bile Duct Neoplasms↗

Coexistence of pemphigus vulgaris and ocular cicatricial pemphigoid.

We describe the case of a patient with both pemphigus vulgaris limited to the oral cavity and ocular cicatricial pemphigoid. The diagnoses were established by means of histopathologic examination and direct and indirect immunofluorescence studies and confirmed by immunoblot analysis of serum. Treatment with dapsone resulted in a prolonged remission of the ocular cicatricial pemphigoid. The pemphigus vulgaris has remained localized to the oral cavity and has responded to sublesional corticosteroid injections.

Conjunctival Diseases↗

Histology and immunopathology of systemic lupus erythematosus affecting the conjunctiva.

Systemic lupus erythematosus (SLE) is an autoimmune disease occasionally involving the conjunctiva, sclera or cornea. The immunopathology of the active epibulbar lesions has not been studied in detail. Conjunctival biopsies from 11 SLE patients with active epibulbar lesions and from 12 age-matched individuals undergoing cataract surgery were analysed by light microscopy, immunofluorescence and immunoperoxidase techniques. SLE patients presented with scleritis (3 cases), peripheral ulcerative keratitis (5 cases) or progressive cicatrising conjunctivitis (5 cases). Histologically, SLE specimens showed moderate subepithelial and perivascular mononuclear cell infiltration or granuloma formation in the substantia propria, and squamous metaplasia; thrombosis was not seen. Immunoreactant deposition was present at the epithelial basement membrane in 4 of 5 cases with cicatrising conjunctivitis. Vascular immunodeposits wer detected in 4 cases. The epithelium showed increased T helper cells (CD4+), granulocytes and natural killer cells (CD67+), dendritic cells (CD1+), and an increase in HLA-DR expression compared with normal tissue. In the substantia propria, B cells (CD22+), macrophages (CD14+), dendritic cells, activated T cells (CD25+, CD3+), the T helper (CD4+)/T suppressor (CD8+) ratio and HLA-DR expression were all increased. These observations suggest that the rare epibulbar manifestations in SLE result from immune-complex-mediated reactions.

Adolescent↗

Mooren's ulcer.

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Corneal Ulcer↗

Cicatricial pemphigoid: diagnosis and treatment.

Cicatricial pemphigoid is a systemic autoimmune disease with both ocular and extraocular manifestations. Its effect on the eyes is characterized by chronic cicatrizing conjunctivitis and progressive conjunctival sub-epithelial fibrosis with resultant fornix foreshortening, symblepharon formation, trichiasis, meibomian, and lacrimal duct obstruction resulting in sicca syndrome, ocular surface keratinization, and eventually blindness. Extraocular manifestations include stricture formation of the esophagus, trachea, anus, or vagina. OCP is characterized by deposition of immunoreactants at the conjunctival basement membrane zone, initiating a type II hypersensitivity reaction. Demonstration of this deposition can be done using immunofluorescence or immunoperoxidase technique.

Autoimmune Diseases↗

Cataract surgery in patients with uveitis.

Until recently, cataract surgery in a patient with uveitis was regarded as a hazardous procedure that yielded unpredictable and often disappointing results. With an increasing number of ophthalmologists recognizing the consequences of chronic low-grade inflammation and therefore treating uveitis patients more aggressively, with a better selection of cases for surgery, and with better surgical techniques, more patients with a history of uveitis who need cataract surgery enjoy a successful outcome than ever before. Careful management and control of inflammation preoperatively and after surgery is critical to success. An in-the-bag posterior chamber lens implant can be part of the surgical plan in selected cases. The aims of the authors in this article are to emphasize the ideas of, intolerance to inflammation, a limited tolerance for steroids to minimize the incidence of cataract and irreversible damage of ocular structures essential to good vision, and strict criteria for selection and management of those patients with uveitis who need cataract surgery.

Cataract↗

Healing corneas express embryonic fibronectin isoforms in the epithelium, subepithelial stroma, and endothelium.

The cornea is a simple, nonvascularized structure, advantageous for studying the molecular components of epithelial and stromal wound repair. Fibronectin (Fn), of uncertain source and composition, accumulates in healing corneas. We postulated that local synthesis of Fn occurs, as exogenous plasma/tear-derived Fn, which lack the embryonic EIIIA and EIIIB segments, have no consistent beneficial effect on healing. Two contrasting corneal wounds were examined by in situ hybridization: a wound of the anterior stroma, basement membrane, and epithelium (anterior excimer laser keratectomy) and a superficial wound restricted to the epithelium that preserved the basement membrane (mechanical scrape). Both wounds heal without scarring. In normal corneas, only the endothelium had detectable Fn mRNA, containing the V and EIIIB domains, sporadically and at low levels. After anterior keratectomies, extensive expression of Fn mRNA occurred in a specific distribution that changed during the phases of healing. Before re-epithelialization (days 1 and 2) V+, EIIIA+, and EIIIB+ isoforms were diffusely found in stromal cells under and adjacent to the wound. After re-epithelialization (days 3 to 42) and reconstitution of laminin in the regenerating basement membrane zone, V+, EIIIA+, and EIIIB+ isoform synthesis was largely restricted to subepithelial stromal cells at the epithelial/stromal interface. In addition, the corneal epithelial cells focally expressed Fn mRNA. The endothelium showed increased levels of V+, EIIIA+, and EIIIB+ Fn mRNA in open and recently re-epithelialized wounds. At 12 weeks after keratectomy, Fn mRNA expression returned to control levels. In contrast, scrape wounds had only a modest increase of stromal and endothelial Fn mRNA (EIIIA+, EIIIB+, and V+) during the first 7 days and no evidence of epithelial Fn synthesis. Embryonic Fn isoforms are synthesized transiently by the cornea in response to even the most superficial wounds and are likely to be relevant to corneal healing and restoration of structure without scar formation.

Animals↗