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Biomedical subjects

Janine A Smith

Publications and source records attributed to Janine A Smith.

At least 19 recordsLinked to original sources
PubMed2006

Hypergammaglobulinemia and corneal opacities in patients with human T-cell lymphotrophic virus type-1.

PURPOSE: To investigate the relationship between serum immunoglobulin levels and corneal opacities in a cohort of patients with human T-cell lymphotrophic virus type-1 (HTLV-1). DESIGN: Retrospective case series. METHODS: Complete ophthalmologic examination was performed on 44 patients with HTLV-1 infection (25 patients with adult T-cell leukemia/lymphoma [ATL], 18 patients with HTLV-1 that was associated myelopathy/tropical spastic paraparesis [HAM/TSP], and one patient who was asymptomatic). Corneal opacities were described by shape, size, color, and location. Serum immunoglobulin (Ig) levels (IgG, IgM, and IgA) were measured by nephelometry. RESULTS: Corneal opacities were identified in 15 of 25 patients (60%) with ATL and five of 18 patients (28%) with HAM/TSP. The prevalence of corneal opacities was associated statistically with elevated IgG level (P = .023) in patients with ATL, but not in patients with HAM/TSP (P > .99). CONCLUSION: Although the mechanism remains unclear, hypergammaglobulinemia is associated with the development of the corneal opacities in patients of African descent with ATL.

Corneal Opacity↗
PubMed2006

Microarray and protein analysis of human pterygium.

PURPOSE: Pterygium is a sunlight-related, ocular-surface lesion that can obscure vision. In order to identify specific genes that may play a role in pterygium pathogenesis, we analyzed the global gene expression profile of pterygium in relation to autologous conjunctiva. METHODS: Oligonucleotide microarray hybridization was used to compare the gene expression profile between human whole pterygium and autologous conjunctiva. Selected genes were further characterized by RT-PCR, western blot, and immunohistochemistry, and comparisons were made with limbal and corneal tissues. RESULTS: Thirty-four genes exhibited a 2 fold or greater difference in expression between human whole pterygium and autologous conjunctiva. Twenty-nine transcripts were increased and five transcripts were decreased in pterygium. Fibronectin, macrophage-inflammatory protein-4 (MIP-4), and lipocalin 2 (oncogene 24p3; NGAL) were increased 9, 5, and 2.4 fold, respectively, while Per1 and Ephrin-A1 were decreased 2 fold in pterygium. Western blots showed that fibronectin and MIP-4 were increased in pterygium compared to limbus, cornea, and conjunctiva. Immunohistochemical analysis showed fibronectin in the stroma; lipocalin 2 in the basal epithelial cells, basement membrane, and extracellular stroma; and MIP-4 in all areas of the pterygium. CONCLUSIONS: These data show both novel and previously identified extracellular-matrix-related, proinflammatory, angiogenic, fibrogenic, and oncogenic genes expressed in human pterygium. Comparisons of selected genes with limbal and corneal tissues gave results similar to comparisons between pterygium and normal conjunctiva. The increased expression of lipocalin 2, which activates matrix metalloproteinases (MMP), is consistent with our previous findings that MMP-9 and other MMPs are highly expressed in pterygium basal epithelium.

Acute-Phase Proteins↗
PubMed2006

Diagnosis and treatment of vasculitis of the central nervous system in a patient with systemic lupus erythematosus.

BACKGROUND: A 23-year-old white woman with a 3-year history of systemic lupus erythematosus and a 15-month history of lupus nephritis and retinal vasculitis was successfully treated with antibiotics for Pseudomonas aeruginosa pneumonia while on moderate doses of corticosteroids. Even though her pneumonia had improved, she developed acute changes in her mental status that rapidly progressed to encephalopathy with coma. INVESTIGATIONS: Physical examination, fundoscopic examination, laboratory tests for metabolic abnormalities, cerebrospinal fluid analysis, microbiology and serologic testing, electroencephalogram, tests for IgM and IgG anticardiolipin antibodies, neuroimaging including CT of the brain and T1-weighted MRI before and after gadolinium contrast, and flow-attenuated inversion recovery MRI. DIAGNOSIS: Vasculitis of the central nervous system associated with systemic lupus erythematosus. MANAGEMENT: Intravenous methylprednisolone 1,000 mg/day for 3 days, one dose of intravenous pulse cyclophosphamide 750 mg/m(2), intravenous immunoglobulin 400 mg/kg/day for 4 days, plasmapheresis on alternate days for five cycles, and prednisone 40 mg/day. She continued monthly doses of intravenous pulse cyclophosphamide and intravenous pulse methylprednisolone for 6 months, followed by maintenance infusions every 3 months over 2 years. Prednisone was tapered over 18 months. Cyclophosphamide was discontinued after 2 years because of poor bone-marrow tolerance, and was replaced with mycophenolate mofetil 3,000 mg/ day and ciclosporin 50 mg twice daily.

Adult↗
PubMed2006

Inhibition of inflammatory cytokine production in human corneal cells by dexamethasone, but not cyclosporin.

PURPOSE: To evaluate the modulatory effects of anti-inflammatory agents, dexamethasone (Dex) and cyclosporin A (CsA), on the production of cytokines and chemokines by human corneal cells in vitro following stimulation by the pro-inflammatory cytokine after interleukin 1beta (IL-1beta). METHODS: A human corneal epithelial (HCE) cell line and human corneal fibroblasts (HCFs) were stimulated in culture with IL-1beta and treated with Dex or CsA. The gene expression for selected cytokines and chemokines was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). The secretion of cytokines and chemokines was measured by enzyme-linked immunosorbent assay. RESULTS: IL-1beta enhanced the mRNA and/or protein levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, and monocyte chemotactic protein (MCP)-1 in HCE and IL-6, IL-8, MCP-3, and regulated on T-cell activation expressed secreted (RANTES) in HCFs. Treatment with CsA did not inhibit cytokine production in either HCE or HCFs. In contrast, Dex treatment inhibited the IL-1beta-induced production of GM-CSF, IL-6, IL-8, MCP-3, and RANTES, but not MCP-1. CONCLUSION: These results show that Dex, but not CsA, has direct immunosuppressive effects on the resident corneal cells, HCE and HCFs. This suggests that the clinically observed immunosuppressive effects of topical CsA are mediated primarily through the immune cells.

Anti-Inflammatory Agents↗
PubMed2005

A randomized, placebo-controlled, double-masked clinical trial of etanercept for the treatment of uveitis associated with juvenile idiopathic arthritis.

OBJECTIVE: To investigate the safety and efficacy of etanercept in the treatment of uveitis associated with juvenile idiopathic arthritis (JIA). METHODS: Children who met the American College of Rheumatology diagnostic criteria for JIA with active uveitis, who had anterior chamber cells of >/=1+ or requiring topical corticosteroid >/=3 times daily, and who were on a stable regimen for arthritis treatment were eligible. Study participants received etanercept (0.4 mg/kg) or placebo administered subcutaneously twice weekly for 6 months. All participants received open-label etanercept for an additional 6 months. RESULTS: Five patients received placebo and 7 received etanercept. Three of the 7 patients treated with etanercept and 2 of the 5 placebo-treated patients were considered ophthalmic successes (P = 1.0). One patient in each treatment group was considered a treatment failure. Three of the 7 etanercept-treated and 2 of the 5 placebo-treated patients were neither successes nor failures by our definition. There were no serious adverse events for any patient during the entire study period. Reports of minor infections were comparable in each treatment group, 71% for etanercept and 60% for placebo (P = 0.58). CONCLUSION: In this small pilot study there was no apparent difference in the anterior segment inflammation between patients treated with etanercept and placebo. The stringent criteria used to measure ophthalmic success of treatment and the small patient population limit the implications of our findings.

Adolescent↗
PubMed2005

X-linked anhidrotic ectodermal dysplasia disruption yields a mouse model for ocular surface disease and resultant blindness.

X-linked anhidrotic/hypohidrotic ectodermal dysplasia (EDA) is caused by mutations in the (EDA) gene, which is required for the morphogenesis of ectoderm-derived tissues. Although EDA function in skin appendage development has been studied in Eda mutant "Tabby" mice, we have recently identified characteristic abnormalities in the ocular surface, an ectoderm-derived tissue. Histology of eyes of Tabby males revealed that 1) as previously reported, mice lacked meibomian glands; 2) >80% developed corneal lesions such as neovascularization, keratitis, ulceration, and keratinization identifiable from 9 weeks of age; and 3) > 80% showed ocular surface inflammation (blepharitis and conjunctivitis) when housed in a standard environment. Strikingly, both corneal defects and inflammation were prevented in Tabby mice bearing a transgene for the Eda-A1 isoform, but meibomian glands were restored little if at all. These findings suggest that intact ocular surface health is EDA dependent and that Tabby corneal abnormalities are not solely dependent on meibomian gland lipid secretion. Alternatively, susceptibility to inflammation and other phenotypes could result from failure of the usual EDA receptor to activate nuclear factor-kappaB transcription factors. This can be further tested in Tabby and Tabby-EDA transgenic mice, which provide unique models of severe ocular surface disease.

Animals↗
PubMed2005

Management of chronic pediatric uveitis.

PURPOSE OF REVIEW: The diagnosis and management of chronic pediatric uveitis can be particularly challenging, with an estimated 25-33% of childhood uveitis cases resulting in severe, life-long visual disability. This paper reviews the recent literature on the management of chronic pediatric uveitis. RECENT FINDINGS: This review highlights recent advances in the diagnosis and medical and surgical management of pediatric uveitis. Several systemic diseases associated with chronic uveitis in children are highlighted, including juvenile idiopathic arthritis, sarcoidosis and Behçet's disease. The treatment of primary ocular diseases associated with chronic pediatric uveitis such as intermediate uveitis and Fuchs' heterochromic iridocyclitis is discussed. The management of infectious causes of pediatric uveitis is not covered in this review. SUMMARY: Knowledge of the ocular complications of chronic pediatric uveitis can help to customize efficacious therapeutic regimens for each patient, maximize the visual potential and minimize complications of these diseases. In addition a close relation should be fostered between pediatricians, pediatric rheumatologists and ophthalmologists to effectively monitor these patients who have multiple medical, surgical and refractive needs. Finally, surgical intervention must be appropriately timed with expert perioperative management of immunosuppressive medications with pediatric concerns in mind.

Adolescent↗
PubMed2004

Comparison of the NEI-VFQ and OSDI questionnaires in patients with Sjögren's syndrome-related dry eye.

BACKGROUND: To examine the associations between vision-targeted health-related quality of life (VT-HRQ) and ocular surface parameters in patients with Sjögren's syndrome, a systemic autoimmune disease characterized by dry eye and dry mouth. METHODS: Forty-two patients fulfilling European / American diagnostic criteria for Sjögren's syndrome underwent Schirmer testing without anesthesia, ocular surface vital dye staining; and measurement of tear film breakup time (TBUT). Subjects were administered the Ocular Surface Disease Index (OSDI) and the 25-item National Eye Institute Vision Functioning Questionnaire (NEI-VFQ). Main outcome measures included ocular surface parameters, OSDI subscales describing ocular discomfort (OSDI-symptoms), vision-related function (OSDI-function), and environmental triggers, and NEI-VFQ subscales. RESULTS: Participants (aged 31-81 y; 95% female) all had moderate to severe dry eye. Associations of OSDI subscales with the ocular parameters were modest (Spearman r (rho) < 0.22) and not statistically significant. Associations of NEI-VFQ subscales with the ocular parameters reached borderline significance for the near vision subscale with TBUT (rho = 0.32, p =.05) and for the distance vision subscale with van Bijsterveld score (rho = 0.33, p =.04). The strongest associations of the two questionnaires were for: ocular pain and mental function with OSDI-symptoms (rho = 0.60 and 0.45, respectively); and general vision, ocular pain, mental function, role function, and driving with OSDI-function (rho = 0.60, 0.50, 0.61, 0.64, 0.57, and 0.67, respectively). CONCLUSIONS: Associations between conventional objective measures of dry eye and VT-HRQ were modest. The generic NEI-VFQ was similar to the disease-specific OSDI in its ability to measure the impact of Sjögren's syndrome-related dry eye on VT-HRQ.

Adult↗
PubMed2004

Pilot clinical trial of dehydroepiandrosterone (DHEA) versus placebo for Sjögren's syndrome.

OBJECTIVE: To screen for potential efficacy and assess feasibility and safety of dehydroepiandrosterone (DHEA) as a treatment for Sjögren's syndrome (SS). METHODS: A 24-week randomized, double-blinded, pilot trial of oral DHEA (200 mg/day) versus placebo was conducted. The primary comparison was to a hypothesized 20% placebo response rate. If 14 consecutive subjects on DHEA did not respond, a Phase III trial would be considered futile. A placebo group of 14 subjects was planned to verify placebo response rate and estimate sample size required for a definitive trial. Response criteria required 20% improvement in at least 2 of 3 domains. Analysis of covariance was used to adjust for baseline differences and for stratified randomization. Outcome measures included visual analog scale questionnaires for dry eye and dry mouth symptoms, lissamine green ocular dye staining and Schirmer I tests, stimulated salivary flow, IgG, and erythrocyte sedimentation rate (ESR). RESULTS: Randomization resulted in 14 DHEA and 14 placebo group subjects. At baseline, mean +/- SD for DHEA versus placebo groups were Schirmer I tests 4.5 +/- 4.5 versus 5.4 +/- 6.1 mm/5 minutes; Van Bijsterveld score 5.3 +/- 2.1 versus 5.5 +/- 2.2; unstimulated saliva 0.03 +/- 0.05 versus 0.04 +/- 0.10 ml/minute; IgG 1,699 +/- 749 versus 1,712 +/- 621 g/dl; and ESR 40 +/- 31 versus 44 +/- 28 mm/hour. Apart from changes over the trial in dry mouth symptoms, no significant differences were noted between the DHEA and placebo groups for dry eye symptoms, objective measures of ocular dryness, stimulated salivary flow; IgG, or ESR. Four DHEA and one placebo group patient dropped out because of adverse effects. Although 7 subjects met response criteria in the DHEA group, 5 met the criteria in the placebo group, and there was no significant difference between groups. CONCLUSION: DHEA showed no evidence of efficacy in SS. Without evidence for efficacy, patients with SS should avoid using unregulated DHEA supplements, since long-term adverse consequences of exposure to this hormone are unknown.

Adjuvants, Immunologic↗
PubMed2004

Dry eye signs and symptoms in women with premature ovarian failure.

OBJECTIVE: To examine whether women with premature ovarian failure (POF) have abnormal findings in ocular surface or tear parameters and whether they report symptoms of ocular discomfort compared with age-matched controls. METHODS: Sixty-five patients with POF and 36 age-matched healthy controls were examined for signs and symptoms of dry eye. The Ocular Surface Disease Index questionnaire and the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) were administered to the participants. Assessments of ocular surface damage (Oxford and van Bijsterveld scores of vital dye staining) and tear status (Schirmer tests 1 [without anesthesia] and 2 [with anesthesia] and tear breakup time) were performed. RESULTS: Women with POF scored significantly worse than controls on all ocular surface damage parameters: Oxford score (3.2 vs 1.7; P =.001), conjunctival lissamine green (2.1 vs 1.3; P =.02), corneal fluorescein staining (1.2 vs 0.4; P =.005), and van Bijsterveld score (2.1 vs 1.3; P =.02). Further, the proportion of patients with POF meeting the dry eye diagnostic criterion of a van Bijsterveld score greater than or equal to 4 was significantly greater among women with POF than among controls (20% vs 3%; P =.02). The POF group also tended to have worse scores than controls on self-reported symptoms, as measured by the overall Ocular Surface Disease Index (12.5 vs 2.1; P<.001) and the overall NEI-VFQ (94 vs 98; P =.001) after adjustment for age and race. Schirmer test scores and tear breakup time did not differ. CONCLUSIONS: Women with POF were more likely to exhibit ocular surface damage and symptoms of dry eye than age-matched controls. They were not, however, more likely to have reduced tear production. To our knowledge, this association between ocular surface disease and POF has not been previously reported. These data provide further evidence of the multifaceted role of sex hormones in the health and disease of the ocular surface.

Adolescent↗
PubMed2004

Etanercept in Sjögren's syndrome: a twelve-week randomized, double-blind, placebo-controlled pilot clinical trial.

OBJECTIVE: To assess the safety and potential efficacy of etanercept in the treatment of Sjögren's syndrome (SS). METHODS: This pilot study was a 12-week randomized, double-blind, placebo-controlled trial of etanercept, with 14 subjects in each group. Patients received 25 mg of etanercept or placebo (vehicle) by twice-weekly subcutaneous injection. Patients met the American-European Consensus Group criteria for SS. The primary outcome required at least 20% improvement from baseline values for at least 2 of the following 3 domains: subjective or objective measures of dry mouth, subjective or objective measures of dry eyes, and IgG level or erythrocyte sedimentation rate (ESR). RESULTS: Of the 14 patients taking etanercept, 11 had primary SS and 3 had SS secondary to rheumatoid arthritis. Baseline measures did not differ between the 2 groups. Three etanercept-treated patients and 1 placebo-treated patient did not complete the trial. Five etanercept-treated patients and 3 placebo-treated patients showed improvement from baseline in the primary outcome variable at 12 weeks, but the difference was not statistically significant. There were no significant differences between the groups for changes in subjective measures of oral or ocular symptoms (by visual analog scale), the IgG level, Schirmer I test result, van Bijsterveld score, or salivary flow. At 12 weeks, the ESR had decreased in the etanercept group compared with baseline (P = 0.004); however, the mean reduction was only 18.6%. CONCLUSION: We found no evidence to suggest that treatment with etanercept at a dosage of 25 mg twice weekly for 12 weeks was clinically efficacious in SS. A larger trial will be necessary to definitively address the efficacy of etanercept in the treatment of SS.

Arthritis, Rheumatoid↗
PubMed2003

Tarsal-conjunctival disease associated with Wegener's granulomatosis.

OBJECTIVE: To describe the clinical characteristics of tarsal-conjunctival disease in a cohort of patients with Wegener's granulomatosis (WG). DESIGN: Retrospective, case-controlled study. PARTICIPANTS: The medical records of 82 consecutive WG patients who underwent an eye examination between January 1996 and June 2002 at the National Institutes of Health were reviewed. METHODS: Details of the ophthalmic examination, results of medical therapy, and histopathologic analysis results were recorded. Tarsal-conjunctival disease was defined by (1). conjunctival hyperemia and granuloma formation, areas of necrosis, or active fibrovascular changes in the tarsus or conjunctiva, or (2). evidence of inactive fibrovascular scar. The association of tarsal-conjunctival disease with major organ system involvement was assessed using Bayesian methods. MAIN OUTCOME MEASURES: The occurrence and clinical characteristics of tarsal-conjunctival disease in a cohort of patients with WG and associations with major organ system involvement. RESULTS: Tarsal-conjunctival disease occurred in 13 of 82 patients (16%) with WG examined over a 6.5-year period. The palpebral surface of the upper lid was involved most commonly, showing conjunctival hyperemia in seven patients, granulomatous lesions in three patients, tarsal-conjunctival necrosis in four patients, active fibrovascular proliferation in six patients, and inactive fibrous scar tissue in seven patients. Histopathologic analysis of eyelid biopsy specimens showed granulomatous inflammation, focal necrosis, and areas of occlusive vasculitis in the tarsus and conjunctiva. In reviewing the patterns of organ involvement in patients with and without tarsal-conjunctival disease, the association of subglottic stenosis and nasolacrimal duct obstruction with tarsal-conjunctival disease showed a high probability of clinical significance. CONCLUSIONS: Tarsal-conjunctival disease, a previously uncommon finding in patients with WG, was characterized by inflammation of the palpebral conjunctiva and tarsus followed by a fibrovascular proliferation and scar formation. Because of the important association of tarsal-conjunctival disease with subglottic stenosis, which can progress and lead to laryngeal obstruction and respiratory failure, patients with tarsal-conjunctival disease should be referred to an otolaryngologist for evaluation.

Adult↗
PubMed2003

Grading of corneal and conjunctival staining in the context of other dry eye tests.

PURPOSE: To describe the Oxford Scheme for grading ocular surface staining in dry eye and to discuss optimization of stain detection using various dyes and filters. Also, to propose a sequence of testing for dry eye diagnosis. METHODS: The grading of corneal and conjunctival staining is described, using the Oxford Scheme, including biomicroscopy, optical filters, illumination conditions, and the characteristics of and instillation techniques used for, selected clinical dyes. RESULTS: A series of panels, labeled A-E, in order of increasing severity, reproducing the staining patterns encountered in dry eye, are used as a guide to grade the degree of staining seen in the patient. The amount of staining seen in each panel, represented by punctate dots, increases by 0.5 of the log of the number of dots between panels B to E. The use of the vital dyes fluorescein, lissamine green, and rose Bengal is described; fluorescein and lissamine green, used in conjunction with appropriate absorption filters, are recommended for use in clinical trials. The placement of staining in relation to the sequence of other diagnostic tests is discussed. CONCLUSIONS: The monitoring and assessment of corneal and conjunctival staining can be greatly enhanced by the use of a grading scale, controlled instillation of dyes, and standard evaluation techniques. This is of particular benefit in clinical trials, where ocular surface staining is commonly employed as an outcome measure

Coloring Agents↗