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Biomedical subjects

S M Whitcup

Publications and source records attributed to S M Whitcup.

At least 91 records · Page 5Linked to original sources
PubMed1996

IL-12 inhibits endotoxin-induced inflammation in the eye.

Interleukin-12 (IL-12) is a heterodimeric cytokine that induces interferon (IFN)-gamma production and an increased generation of Th1 cells. Both IL-12 and IL-12 antagonists are being studied for the treatment of allergic reactions, autoimmune disease and malignancy. The goal of the present experiments was to examine the importance of IL-12 in endotoxin-induced ocular inflammation. The number of inflammatory cells infiltrating eyes with endotoxin-induced uveitis (EIU) was significantly increased in animals treated with intraperitoneal anti-IL-12 antibody when compared to control animals, but there was no difference in infiltrating inflammatory cells in the eyes of animals treated with IL-12 when compared to controls. In contrast, intraocular injection of IL-12 significantly inhibited the development of endotoxin-induced intraocular inflammation. The infiltrating inflammatory cells were reduced in the eyes of animals receiving intraocular IL-12 when compared to controls. Cytokine analysis of the aqueous humor obtained from eyes with EIU showed increased levels of IFN-gamma and decreased levels of IL-6 in eyes receiving intraocular IL-12. These data show that IL-12 has an inhibitory effect on endotoxin-induced inflammation in the eye and suggest that IL-12 can have an immunoregulatory function in some forms of inflammatory disease.

Animals↗
PubMed1996

Association of thyroid disease with retinitis pigmentosa and gyrate atrophy.

PURPOSE: To compare the prevalence of thyroid disease in patients with retinitis pigmentosa, in patients with gyrate atrophy of the choroid and retina, and in patients with no history of ocular disease. METHOD: Forty-four patients with retinitis pigmentosa, 34 patients with gyrate atrophy, and 30 normal control patients with no ocular disease were evaluated in a case-control study for the presence of thyroid disease. RESULTS: Thyroid disease was diagnosed in six of 44 patients with retinitis pigmentosa and seven of 34 patients with gyrate atrophy but in only one of 30 control patients. Compared with control patients, the odds ratio for the occurrence of thyroid disease was 6.2 for patients with retinitis pigmentosa and 12.7 for patients with gyrate atrophy. CONCLUSION: These data suggest an increased occurrence of thyroid disease in patients with retinitis pigmentosa and gyrate atrophy.

Adolescent↗
PubMed1996

A randomized, masked, cross-over trial of acetazolamide for cystoid macular edema in patients with uveitis.

PURPOSE: To study the effect of acetazolamide on cystoid macular edema in patients with uveitis. METHODS: Forty patients with chronic intermediate, posterior, or panuveitis associated cystoid macular edema were randomized into a masked, cross-over trial comparing acetazolamide versus placebo. Patients received an initial 4-week course of either acetazolamide or placebo (course A) followed by a 4-week washout period. They then received a 4-week course of the opposite study medication (course B). Primary endpoints included area of cystoid macular edema measured on late-phase views of fluorescein angiography and visual acuity. RESULTS: Thirty-seven patients completed the trial and were available for analysis; 17 (46%) were randomized to receive acetazolamide and 20 (54%) to receive placebo during course A. Acetazolamide resulted in a 0.5-disc area (25%) decrease in cystoid macular edema over that of placebo (P = 0.01; estimated treatment effect = -0.5 disc areas; 95% confidence interval, -0.9 to -0.1). However, there was no statistically significant effect of acetazolamide on visual acuity (P = 0.61; estimated treatment effect = 0.6 letters; 95% confidence interval, -2 to 3). CONCLUSIONS: A 4-week course of acetazolamide therapy results in a statistically significant but small decrease in cystoid macular edema in patients with chronic uveitis, and does not improve visual acuity. In contrast to previous studies in the literature, acetazolamide may have a more limited clinical benefit in patients with long-standing cystoid macular edema associated with chronic uveitis.

Acetazolamide↗
PubMed1996

Primary retinal vasculitis. Systemic associations and diagnostic evaluation.

BACKGROUND: Inflammation of the retinal vasculature without an infectious etiology, systemic disease association, or concomitant ocular disease is termed primary retinal vasculitis, and can result in severe and permanent vision loss. Patients with primary retinal vasculitis usually are subjected to an extensive but unrewarding diagnostic evaluation. This study was undertaken to determine the value of such a diagnostic workup, and to determine whether systemic diseases develop in these patients during the course of their illness. METHODS: The clinical records of 25 patients seen between 1984 and 1994 with the referring diagnosis of primary retinal vasculitis were reviewed retrospectively. Recorded data included patient age, sex, race, medical history, medications, visual acuity, extent of retinal disease, and the results of their diagnostic evaluations. RESULTS: On presentation, none of the patients had an underlying systemic disease attributable as the cause of their retinal vasculitis. Review of systems was suggestive of an underlying systemic disease in 1 of 25 patients. Diagnostic evaluation in this patient showed a positive antinuclear antibody value and a double-stranded DNA, suggestive of systemic lupus erythematosus. Subsequently, systemic lupus erythematosus was diagnosed based on the development of other diagnostic criteria. The review of systems was not suggestive of an underlying systemic disease in 24 of 25 patients. False-positive diagnostic test results were obtained in 5 (20.8%) of these 24 patients. No underlying systemic disease associated with the patients' retinal vasculitis subsequently developed in any of these five patients (mean follow-up, 4 years). CONCLUSION: Few diagnostic tests should be ordered in patients with retinal vasculitis in the absence of a medical history suggestive of underlying systemic disease.

Adolescent↗
PubMed1996

Compound 48/80-induced conjunctivitis in the mouse: kinetics, susceptibility, and mechanism.

A mouse model of conjunctivitis has been developed by topical application of compound 48/80 (C48/80), an agent that triggers mast cell degranulation. We examined the responsiveness of C57BL/6, C3H/HeN, and ASW/J mouse strains to C48/80 stimulation, and of a mutant strain with mast cell depletion (WBB6F1/J and its sham control). Conjunctivae were collected and examined histopathologically at 15 min and 1,6,24,48 and 72 h after topical C48/80 administration. Conjunctival inflammation developed in all strains, although the severity varied. The conjunctivitis was characterized clinically by irritation, discharge, erythema, and chemosis. Pathology showed conjunctival infiltration with neutrophils, macrophages, CD4+ T lymphocytes, and a few eosinophils. Degranulation of mast cells and evacuation of goblet cells were also observed. Late-phase inflammatory reactions peaked 6-24 h after C48/80 administration and resolved by 48-72 h. WBB6F1/J mice had much less inflammation than their sham controls. In conclusion, topical C48/80 induced a conjunctival inflammatory response similar to allergen-induced conjunctivitis. The depletion of mast cells significantly reduced the inflammation. This model which consistently mimics the clinical signs and histopathological processes of allergic conjunctivitis in humans, is practical and reliable for the evaluation of new anti-allergic medications and for the investigation of conjunctival cellular responses in the allergic inflammatory cascade.

Animals↗
PubMed1996

Topical cyclosporine inhibits mast cell-mediated conjunctivitis.

PURPOSE: Allergic conjunctivitis is a common condition caused by a mast cell-mediated hypersensitivity reaction to immunoglobulin E-bound allergens. The purpose of this study was to investigate the effect of topical cyclosporine A on the development of mast cell-mediated conjunctivitis in mice. METHODS: Allergic conjunctivitis was induced in C57BL/6 mice by topical applications of compound 48/80, a mast cell degranulating agent. In two separate experiments, mice were treated with topical cyclosporine A (0.05%, 0.2%, or 0.4%), prednisolone acetate 1%, or phosphate-buffered saline. Twenty-four hours after compound 48/80 instillation, the number of neutrophils, eosinophils, lymphocytes, macrophages, and the number of preserved goblet cells and undegranulated mast cells in the conjunctiva were counted by a masked observer. RESULTS: In both experiments, treatment with all three doses of cyclosporine A resulted in a statistically significant reduction in the number of infiltrating neutrophils and eosinophils compared to saline-treated controls. There was no significant difference in the treatment effect of cyclosporine and prednisolone acetate. In addition, there was increased preservation of goblet cells in the cyclosporine A-treated animals. Immunohistochemical staining showed a reduction in infiltrating lymphocytes and a smaller reduction in infiltrating macrophages in animals treated with cyclosporine compared to saline-treated controls. CONCLUSIONS: Topical cyclosporine A was effective in inhibiting the development of mast cell-mediated allergic conjunctivitis in mice. This study suggests that topical cyclosporine A may be effective in treating allergic conjunctivitis in humans.

Administration, Topical↗
PubMed1995

32 cases of sympathetic ophthalmia. A retrospective study at the National Eye Institute, Bethesda, Md., from 1982 to 1992.

OBJECTIVE: To examine the relationship between visual outcome and the clinical management of patients with sympathetic ophthalmia. METHODS: Thirty-two patients with sympathetic ophthalmia who were seen at the National Eye Institute, Bethesda, Md, between 1982 and 1992, were retrospectively reviewed. RESULTS: There were equal numbers of males and females. Sympathetic ophthalmia occurred after trauma in 23 patients and surgery in nine patients. Sixteen of the 32 patients had a final visual acuity of 20/40 or better; 10 patients had a visual acuity worse than 20/200. Good visual outcome was associated with early and aggressive treatment with corticosteroids, sometimes in combination with other immunosuppressive agents. Poor visual acuity was associated with glaucoma, chorioretinal scars in the macula, and persistent uncontrolled inflammation. CONCLUSION: Prompt and aggressive use of antiinflammatory therapy can improve the visual outcome of patients with sympathetic ophthalmia.

Adolescent↗
PubMed1995

The relationship between visual acuity and functioning and well-being among diabetics.

Given the enormous recent interest in functional capabilities related to vision, the goal of this study was to examine the relationship of standard clinical measures of vision (e.g. Snellen acuity) to functioning and well-being. The association between Snellen visual acuity, Amsler grid distortion and presence of diabetic retinopathy with self-reported functioning and well-being (SF-36) were examined in a sample of 327 diabetics from the Medical Outcomes Study (MOS). There was little or no correlation between Snellen visual acuity, Amsler grid distortion or diabetic retinopathy and functioning and well-being (i.e. SF-36 scales). Maximum product-moment correlation was 0.15 with worst eye visual acuity, 0.13 with best eye visual acuity, 0.08 with presence of retinopathy, and 0.10 with Amsler grid distortion. Analysis of variance revealed that visual acuity (both best and worst eye) was statistically related only to the physical function scale; no other exam measure was related to any other SF-36 scale score. Snellen visual acuity, Amsler distortion and diabetic retinopathy correlate weakly with patient self-reported functioning and well-being. Thus, the information provided by functioning and well-being measures is complementary to that of standard clinical measures of visual ability.

Activities of Daily Living↗
PubMed1995

Interleukin-10 in the vitreous of patients with primary intraocular lymphoma.

PURPOSE: To find an accurate and simple method to diagnose primary intraocular lymphoma. METHODS: We prospectively analyzed concentrations of interleukin-10, interleukin-1, interleukin-2, interleukin-4, and interleukin-6 in vitrectomy specimens from three patients with primary intraocular lymphoma and five patients with uveitis by enzyme-linked immunosorbent assay. RESULTS: Interleukin-10 in the vitreous was detected in patients with primary intraocular lymphoma. Interleukin-10 levels correlated with clinical activity and the number of malignant cells. CONCLUSION: Concentrations of interleukin-10 in the vitreous may be a helpful clue to both clinicians and pathologists in diagnosing primary intraocular lymphoma.

Enzyme-Linked Immunosorbent Assay↗
PubMed1995

Monoclonal antibodies against CD54 (ICAM-1) and CD11a (LFA-1) prevent and inhibit endotoxin-induced uveitis.

We studied the effect of monoclonal antibodies (mAbs) against CD54 (intercellular adhesion molecule-1; ICAM-1) and CD11a (lymphocyte function-associated antigen-1; LFA-1) on the prevention and treatment of endotoxin-induced uveitis (EIU). When treated at the time of endotoxin injection the mean number of inflammatory cells infiltrating the eye +/- S.E.M. on histologic sections was 469.2 +/- 51.9 for controls, 13.8 +/- 2.6 for rats receiving anti-ICAM-1 mAb (P < 0.0001), and 195.8 +/- 48.8 for rats receiving anti-LFA-1 mAb (P = 0.0003). When treated after the start of inflammatory disease, the mean number of infiltrating inflammatory cells +/- S.E.M. was 273.0 +/- 30.7 for controls, 6.4 +/- 1.7 for rats receiving anti-ICAM-1 mAb (P < 0.0001), and 54.2 +/- 7.6 for rats receiving anti-LFA-1 mAb (P < 0.0001). The mean number of cells per milliliter of aqueous humor +/- S.E.M. was 1867.6 +/- 321.8 for controls, 21.7 +/- 5.3 for rats receiving anti-ICAM-1 mAb (P < 0.0001), and 295.1 +/- 71.2 for rats receiving anti-LFA-1 mAb (P < 0.0001). MAbs against ICAM-1 and LFA-1 significantly inhibited the development of EIU and were effective in treating clinically evident ocular inflammatory disease.

Animals↗
PubMed1995

Endotoxin induced uveitis in the mouse: susceptibility and genetic control.

Endotoxin induced uveitis in the mouse provides a useful animal model for acute anterior uveitis in humans. We have investigated the susceptibility of endotoxin-induced uveitis among various mouse strains, and have examined the relationship between genetic background and the resultant inflammatory response to endotoxin. We studied ten strains with differing major histocompatibility-2 genes, lipopolysaccharide response gene, and strains with mast cell depletion and its sham control. Anterior uveitis was induced by injecting 300 micrograms of Salmonella typhimurium endotoxin into one hind footpad. Mice were then killed 8, 12, 16, 20, 24, 48 and 72 hr after endotoxin injection, and vertical sections of the eyes through the pupil-optic nerve axis were evaluated for ocular inflammation. C3H/HeN mice developed severe uveitis. In contrast, C3H/HeJ mice (lipopolysaccharide response gene-) did not develop uveitis even though it has the same genetic background and shares the same major histocompatibility-2 haplotype with C3H/HeN mice (lipopolysaccharide response gene+). The strain that was mast-cell deficient (W/Wv) developed minimal uveitis; however, W/+ mice, with mast cells, developed more inflammation at 48 and 72 hr after endotoxin injection. C3H.SW and FVB/N mice also developed severe uveitis, and BALB/C, CBA/J, and B10.A developed mild uveitis. In conclusion, there is a wide variation in the magnitude and susceptibility to endotoxin among mouse strains. Multiple factors appear to influence this variability, including non-histocompatibility-2 genetic background, the lipopolysaccharide response gene, and the presence of mast cells.

Animals↗
PubMed1995

Combined intravenous ganciclovir and foscarnet for children with recurrent cytomegalovirus retinitis.

PURPOSE: Children with the acquired immune deficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis may not complain of symptoms despite the presence of advanced sight-threatening disease. Although little data exist regarding CMV retinitis in this population, the treatment of this disease may be difficult because of frequent, extensive recurrences after reduction of drug dose from induction to maintenance levels. The authors reported the results of the use of combined ganciclovir and foscarnet for treatment of recurrent CMV retinitis in three children with AIDS. METHODS: Three children with recurrent CMV retinitis were treated with combined ganciclovir and foscarnet administered intravenously. All patients initially received induction dosages of ganciclovir followed by maintenance therapy, at which time they experienced reactivation of their disease. The dosing regimen for induction with the combined therapy was foscarnet (60 mg/kg every 8 hours) and ganciclovir (5 mg/kg daily for 3 weeks). Maintenance with combined therapy consisted of foscarnet (90 mg/ kg daily) and ganciclovir (5 mg/kg daily). RESULTS: All patients showed complete healing of the retinitis during the first 3 weeks of combined therapy. Median survival after initiation of combined therapy was 15 weeks (range, 12-33 weeks). None of the children experienced reactivation of CMV retinitis during combined therapy with ganciclovir and foscarnet. Combined therapy was well tolerated in all patients without major side effects. No patient required discontinuation or interruption of either drug during combined therapy. CONCLUSION: Children with recurrent CMV retinitis may not report visual symptoms, which can delay therapeutic intervention. Therefore, recurrent disease in children should be treated aggressively to avoid potentially devastating visual loss. A combination of ganciclovir and foscarnet appears to be a safe and effective therapeutic option for treatment of recurrent CMV retinitis in children with AIDS. This approach causes no additional toxic reactions and may provide improved long-term control of recurrent CMV retinitis in children.

AIDS-Related Opportunistic Infections↗
PubMed1995

The diagnosis and management of uveitis.

The diagnosis and management of uveitis is complicated and challenging. The protean signs and symptoms seen in patients with uveitis may lead to a diagnostic dilemma. A carefully taken history with particular attention to demographic factors and meticulous physical examination are crucial to guiding diagnostic testing. Tailoring the diagnostic approach in patients with uveitis frequently yields useful data in contrast to blanketing every possible uveitic entity. It is also important to distinguish among various aetiologies, including infectious and neoplastic causes which may respond to specific therapy. Medical treatment of noninfectious uveitis must have clear objectives including reduction of inflammation, relief of symptoms and restoration of visual functioning. Familiarity with possible symptoms and signs of adverse drug reactions is essential early in the course of treatment so that their effects may be minimised. Appropriate therapy of presumed autoimmune uveitis is based on disease severity, presence or absence of bilateral disease and the health status of the patient.

Administration, Topical↗
PubMed1995

Effects of topical FK506 on endotoxin-induced uveitis (EIU) in the Lewis rat.

FK506 is a macrolide antibiotic and a potent immunosuppressant. To investigate the effect of topical FK506 on acute ocular inflammation, we evaluated its action on the development of endotoxin-induced uveitis (EIU). At two different concentrations of 0.05% and 0.3%, topical FK506 was applied to Lewis rats with EIU. In aqueous, the mean number of inflammatory cells per microliter +/- SEM was 2,389 +/- 1,277, 1,571 +/- 1,562, 898 +/- 882, and 69 +/- 152 for rats treated with vehicle alone, 0.05%, 0.3% FK506, and 1% prednisolone acetate. The median of histological grades was 2, 1.5, 0.8, and 0.5 for animals treated with these 4 different regimens respectively. Analysis of aqueous protein showed a small reduction in FK506-treated animals. Mean blood levels of FK506 were low in rats treated with topical FK506 (0.05%, 0.84 ng/ml; 0.3%, 2.0 ng/ml) suggesting that its therapeutic effect was not secondary to the systemic absorption of the drug. Although FK506 is not as effective as prednisolone, 0.3% FK506 produced significant decreases in the mean aqueous inflammatory cell number and histological inflammatory score as compared to control vehicle alone. We conclude that topical FK506 can suppress EIU in a dose-dependent fashion and may be an alternative medication for patients with anterior uveitis and contra-indication to topical steroid.

Administration, Topical↗
PubMed1994

Combined cyclosporine and corticosteroid therapy for sight-threatening uveitis in Behçet's disease.

Behçet's disease is a multisystem disorder that may cause profound ocular inflammation and blindness. We reviewed 19 patients with severe ocular Behçet's disease treated with combined cyclosporine and corticosteroid therapy. Previous treatment with corticosteroids alone failed to control the uveitis in all patients. Ten patients were given cyclosporine therapy alone (mean dosage, 8.6 mg/kg of body weight per day), and nine patients were given lower dosages of cyclosporine (mean dosage, 6.2 mg/kg of body weight per day) in combination with prednisone (mean dosage, 29.4 mg per day). The mean follow-up on therapy was 51 months. After three months of therapy, a trend toward greater improvement in visual acuity was noted in patients treated with combined cyclosporine and prednisone compared to those receiving cyclosporine alone (17.8 letters vs 10.2 letters, P = .2379), but after one year little difference was observed in the improvement between the two groups (5.8 letters vs 3.3 letters, P = .7984). However, a trend toward greater renal toxicity was seen in patients treated with cyclosporine alone after both three months and one year of therapy. Because of either a suboptimal therapeutic response or adverse effects, all patients treated with cyclosporine alone at baseline had prednisone added to their regimen after a mean time of 23.5 months. Overall, visual acuity remained stable or improved in 28 of 37 eyes (75.7%) over the course of therapy. These data suggest that combined cyclosporine and prednisone therapy is an effective treatment for Behçet's uveitis and may be less toxic than therapy with cyclosporine alone. A prospective, randomized trial with a larger sample size is needed to provide definitive data.

Adolescent↗
PubMed1994

A clinicopathologic report of the retinal lesions associated with didanosine.

Didanosine, a purine analogue with antiretroviral activity, is used in the treatment of human immunodeficiency virus disease. Associated toxic effects of didanosine include pancreatitis, peripheral neuropathy, and retinopathy. The retinal lesions associated with didanosine therapy were studied in a 6-year-old girl with acquired immunodeficiency syndrome. Gross examination disclosed multiple well-circumscribed depigmented lesions in the midperipheral retina. Microscopic examination of these lesions showed multiple areas of retinal pigment epithelial (RPE) loss, some surrounded by areas of hypertrophy or hypopigmentation of the RPE. Partial loss of the choriocapillaris and neurosensory retina were also noted in areas of diseased RPE. Transmission electron microscopy showed numerous membranous lamellar inclusions and cytoplasmic bodies in the RPE cells. These data show that didanosine primarily affects the RPE and that the choriocapillaris and overlying neurosensory retina are also dystrophic in areas of RPE loss.

Child, Preschool↗
PubMed1994

Experimental melanin-protein-induced uveitis in the Lewis rat. Immunopathologic processes.

PURPOSE: To study the immunopathology of experimental melanin-protein-induced uveitis in the Lewis rat. METHODS: Rats were immunized with bovine ocular melanin protein. The kinetics of experimental melanin-protein-induced uveitis was studied by clinical examination and immunopathology. Cellular and humoral responses were evaluated by lymphocyte proliferation, delayed-type hypersensitivity, and agglutination. After clinical disease subsided, recurrent experimental uveitis was induced with a low-dose footpad injection of lipopolysaccharide. RESULTS: Experimental melanin-protein-induced uveitis was characterized by bilateral uveal infiltration mainly with lymphocytes and monocytes. Delayed-type hypersensitivity, lymphocyte proliferation, and agglutination to bovine ocular melanin protein were positive. Expressions of major histocompatibility complex class II and intercellular adhesion molecule-1 were observed before ocular infiltration. The predominantly infiltrating cells were CD4+ lymphocytes. Experimental melanin-protein-induced uveitis subsided within 1 month, spontaneously recurred within 1 week in approximately one quarter of the rats, and was inducible in most rats with 5 micrograms of lipopolysaccharide confirmed by histopathology. CONCLUSIONS: Experimental melanin-protein-induced uveitis is a T-cell-mediated autoimmune uveitis, resembling noninfectious recurrent iridocyclitis and choroiditis in humans.

Animals↗