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Biomedical subjects

S M Whitcup

Publications and source records attributed to S M Whitcup.

At least 37 records · Page 2Linked to original sources
PubMed2000

Recurrent intraocular inflammation in endotoxin-induced uveitis.

PURPOSE: Endotoxin-induced uveitis (EIU) in rats and mice peaks 24 hours after endotoxin injection and is commonly assumed to be a monophasic disease. This study examined intraocular inflammation at later time points to determine whether endotoxin injection can induce recurrent intraocular inflammation in strains of mice with high or moderate levels of susceptibility to EIU. METHODS: EIU was elicited in two mouse strains with high (C3H/HeN) and moderate (FVB/N) susceptibility, by means of intraperitoneal injections of Salmonella typhimurium endotoxin. Inflammatory cells in the anterior and posterior segments of the eye were counted by a masked observer on histologic sections of eyes from 1 to 17 days after endotoxin injection. RESULTS: A bimodal distribution of inflammatory cell infiltration was noted in eyes from C3H/HeN mice. As previously reported, inflammation peaked at 24 hours after endotoxin injection. However, a second, more pronounced peak of intraocular inflammation occurred approximately 5 days after endotoxin injection. FVB/N mice had a single peak of intraocular inflammation 4 days after injection. CONCLUSIONS: Endotoxin injection in C3H/HeN elicits recurrent intraocular inflammation. The previously unrecognized second peak of inflammation is more severe than the initial inflammatory disease. Studies on this second inflammatory peak may be useful in determining the pathogenesis of recurrent uveitis in humans.

Animals↗
PubMed2000

Utility-based estimates of the relative morbidity of visual impairment and angina.

PURPOSE: To quantify and compare the reduction in quality of life due to visual impairment and angina using patient preferences (utilities). METHODS: Using a standard time tradeoff method, we obtained utilities for current vision, monocular and binocular blindness, current angina, and moderate angina in 60 patients with both vision problems and angina pectoris who sought care at the National Eye Institute (NEI), National Naval Medical Center, or Barnes-Jewish Hospital. Patients were characterized clinically based on visual acuity and the Duke Activity Status Index (DASI). Patients also completed a seven-item version of the NEI Visual Functioning Questionnaire and the SF-36 Health Survey Questionnaire. RESULTS: Patients had a median visual acuity of 20/100 in the worst eye, 20/40 in the better eye, and a median DASI of 24.2 (0 = severe functional limitations due to anginal symptoms, 58.2 = no limitations). There was substantial variation in utilities among patients. The average utility for current vision (relative to ideal vision [= 1.0] and death [= 0.0]) was 0.82; the average utility for current angina (relative to no angina symptoms [= 1.0] and death [ = 0.0]) was 0.89. Among 26 patients with both visual impairment and recent anginal symptoms, the decrement in utility (on a scale ranging from ideal health [= 1.0] to death [= 0.0]) imposed by current visual impairment was greater than that imposed by current angina symptoms (0.146 versus 0.072, p=0.08, Wilcoxon signed rank test). The decrement in utility associated with binocular blindness was greater than the decrement associated with the symptoms of moderate angina (0.477 versus 0.039, p<0.0001). CONCLUSIONS: Clinical status is not a surrogate for patient preferences regarding vision impairment or angina. There is substantial variation in utilities within the study population for both experienced and theoretical impairment states which is not explained by variations in clinical status. Some states of visual impairment may pose a greater quality of life burden than anginal symptoms. Because patient preferences for vision vary greatly, individual assessment is warranted for consideration in therapeutic decision making.

Aged↗
PubMed2000

Apoptosis in cytomegalovirus retinitis associated with AIDS.

PURPOSE: To determine the role of apoptosis in the pathogenesis of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. METHODS: Forty-three eyes from patients with cytomegalovirus retinitis treated before the introduction of highly active anti-retroviral therapy were examined by routine histopathology and in situ techniques to detect apoptosis (TUNEL assay). Apoptosis was graded on a scale from 0 to 3+ by quantitating the number of TUNEL positive cells per case using a standard grading procedure. Statistical analysis describing the association between apoptosis grade and the proportions of eyes with active CMV infection, with choroidal inflammation and treated with the sustained-release intravitreal ganciclovir implant was performed using the Armitage procedure. RESULTS: Apoptosis in both CMV infected and uninfected retinal cells was detected in 28 of 41 eyes (68%); 13 (45%) with active and 15 (55%) with inactive cytomegalovirus retinitis. The degree of apoptosis was mild (1+) in 14 eyes, moderate (2+) in 6 eyes and severe (3+) in 8 eyes. Apoptosis was not identified in two eyes without CMVR. An increase in apoptosis grade was positively associated with active CMVR (p = 0.014). There was no significant association between apoptosis and choroidal inflammation. The presence and the severity of apoptosis was less in eyes treated with the sustained-release intravitreal ganciclovir implant compared to those treated with systemic anti-viral therapy, however, the difference was not statistically significant. CONCLUSIONS: Apoptosis contributes to retinal cell loss in eyes with cytomegalovirus retinitis associated with AIDS but did not correlate with the progressive loss of retinal cell function in patients with treated, inactive CMVR.

AIDS-Related Opportunistic Infections↗
PubMed1999

Discontinuation of anticytomegalovirus therapy in patients with HIV infection and cytomegalovirus retinitis.

CONTEXT: Persons with cytomegalovirus (CMV) retinitis and acquired immunodeficiency syndrome (AIDS) have required lifelong anti-CMV therapy to prevent the progression of retinal disease and subsequent loss of vision. OBJECTIVE: To determine whether patients who were taking highly active antiretroviral therapy (HAART) and who had stable CMV retinitis could safely discontinue anti-CMV therapy without reactivation of their retinitis or increase in human immunodeficiency virus (HIV) viral load. DESIGN: Prospective nonrandomized interventional trial performed from July 1997 to August 1999. SETTING: Clinical Center of the National Institutes of Health, Bethesda, Md. PATIENTS: Fourteen patients with stable CMV retinitis and HIV infection and CD4+ cell counts higher than 0.1 5 x 10(9)/L and being treated with systemic anti-CMV medications and HAART. INTERVENTIONS: Discontinuation of specific anti-CMV therapy. MAIN OUTCOME MEASURES: Reactivation of CMV retinitis, development of extraocular CMV infection, detection of CMV in blood and urine, HIV burden, immunologic function, quality of life, morbidity, and mortality. RESULTS: Twelve (89.7%) of 14 patients had evidence of immune recovery uveitis before anti-CMV drugs were discontinued. No patient had reactivation of CMV retinitis or development of extraocular CMV disease during mean follow-up of 16.4 months (range, 8.3-22.0 months) without anti-CMV therapy. Human immunodeficiency viral load remained stable following cessation of anti-CMV medications. Blood and urine assays for CMV were briefly positive in 9 patients but did not predict reactivation of CMV disease. Worsening immune recovery uveitis was associated with a substantial (>3 lines) vision loss in 3 patients. CONCLUSIONS: Maintenance anti-CMV medications were safely stopped in those patients who had stable CMV retinitis and elevated CD4+ cell counts and who were taking HAART. The study demonstrates that immune recovery following potent antiretroviral therapy is effective in controlling a major opportunistic infection, even in patients with a history of severe immunosuppression.

AIDS-Related Opportunistic Infections↗
PubMed1999

Treatment of noninfectious intermediate and posterior uveitis with the humanized anti-Tac mAb: a phase I/II clinical trial.

To evaluate the safety and potential therapeutic activity of humanized anti-IL-2 receptor mAb (Daclizumab) therapy in the treatment of patients with severe, sight-threatening, intermediate and posterior noninfectious uveitis, a nonrandomized, open-label, pilot study was performed. Patients with uveitis were treated with a minimum of 20 mg of prednisone, cyclosporine, antimetabolites, or any combination of these agents were eligible. Patients were weaned off their systemic immunosuppressive agents according to a standardized schedule, while ultimately receiving Daclizumab infusions every 4 weeks. Anti-IL-2 receptor antibody therapy, given intravenously with intervals of up to 4 weeks in lieu of standard immunosuppressive therapy, appeared to prevent the expression of severe sight-threatening intraocular inflammatory disease in 8 of 10 patients treated over a 12-month period, with noted improvements in visual acuity. One patient met a primary endpoint with a loss of vision of 10 letters or more from baseline in one eye and another patient discontinued therapy because of evidence of increased ocular inflammation. All patients were able to tolerate the study medications without the need for dose reduction. We report effective long-term use of anti-IL-2 therapy for an autoimmune indication. These initial findings would suggest that anti-IL-2 receptor therapy may be an effective therapeutic approach for uveitis and, by implication, other disorders with a predominant Th1 profile.

Adult↗
PubMed1999

Primary intraocular lymphoma with a low interleukin 10 to interleukin 6 ratio and heterogeneous IgH gene rearrangement.

Primary intraocular lymphoma is almost always a central nervous system B-cell non-Hodgkin lymphoma. Primary intraocular lymphoma is commonly diagnosed by demonstrating lymphoma cells in the vitreous or cerebrospinal fluid. An interleukin (IL) 10 to IL-6 ratio greater than 1.0 in these fluids and the detection of immunoglobulin gene rearrangement are useful adjuncts in the diagnosis of primary intraocular lymphoma. We report a case of primary intraocular lymphoma diagnosed by chorioretinal biopsy in which no malignant cells were identified in the vitreous and in which the IL-10 to IL-6 ratio was less than 1.0. The detection of IgH gene rearrangement heterogeneity in the tumor cells by polymerase chain reaction, a high tumor mitotic figure rate, and the rapid onset of multiple brain lesions suggest an aggressive malignant neoplasm.

Adult↗
PubMed1999

Blocking ICAM-1 (CD54) and LFA-1 (CD11a) inhibits experimental allergic conjunctivitis.

Cell adhesion molecules are critical for the homing and migration of leukocytes into inflamed tissues. We investigated the role of ICAM-1 and LFA-1 in a previously described experimental model of ragweed (Rw)-induced allergic conjunctivitis. SWR/J mice were treated intraperitoneally 6 and 1 h prior to topical challenge with Rw with injections of anti-ICAM-1 monoclonal antibody (mAb), anti-LFA-1 mAb, both anti-ICAM-1 and anti-LFA-mAbs, or rat IgG. Blocking ICAM-1 or LFA-1 reduced the clinical signs of allergic conjunctivitis. Treatment with anti-ICAM-1 or anti-LFA-1 mAbs also significantly inhibited cellular infiltration into the conjunctiva. The greatest inhibitory effect was achieved with the combination of antibodies against both cell adhesion molecules. Since antibodies against ICAM-1 and LFA-1 significantly inhibit the development of the clinical and histologic signs of allergic conjunctivitis, they may be useful for treating patients with ocular allergy.

Animals↗
PubMed1999

Subretinal fibrosis and choroidal neovascularization in Vogt-Koyanagi-Harada syndrome.

BACKGROUND: To describe clinical findings of subretinal fibrosis and choroidal neovascularization in patients with Vogt-Koyanagi-Harada (VKH) syndrome. METHODS: We retrospectively reviewed 75 medical records of patients with VKH seen at the National Eye Institute, Bethesda, Maryland between 1978 and 1996. Recorded data included age, gender, race, duration of disease, extraocular manifestations, best-corrected visual acuity, slit-lamp biomicroscopy, retinal examination, retinal photographs and fluorescein angiograms. We sought features that correlated with the visual outcome. RESULTS: Thirty of 75 (40%) patients developed subretinal fibrosis. Eleven patients (14.7%) had choroidal neovascularization. Presence of subretinal fibrosis was associated with a longer duration of the disease (42.6 vs 19.1 months, P = 0.07). Patients with subretinal fibrosis had worse visual acuity than those without subretinal fibrosis (26.2 vs 57.3 ETDRS letters read, P < 0.001) after adjusting for duration of disease (P = 0.021), degree of vitreous haze (P = 0.074), and use of immunosuppressive therapy (P = 0.008). CONCLUSIONS: Presence of subretinal fibrosis in patients with VKH is associated with a poor visual prognosis. The diagnosis of choroidal neovascularization and subretinal fibrosis presents a challenge in the management of this disease.

Adult↗
PubMed1999

Corneal endothelial deposits in children positive for human immunodeficiency virus receiving rifabutin prophylaxis for Mycobacterium avium complex bacteremia.

PURPOSE: To assess the potential ocular effects of prophylactic administration of rifabutin in children with symptomatic human immunodeficiency virus (HIV) infection and CD4 counts less than 50 cells per mm3. METHODS: Twenty-five children with HIV infection were enrolled in a phase I-II study of prophylactic administration of systemic rifabutin for prevention of disseminated Mycobacterium avium complex infection and monitored prospectively for the development of ocular complications secondary to HIV infection or drug toxicity. RESULTS: The dose of rifabutin ranged from 5.0 mg to 15.0 mg per kg, and the median ophthalmic follow-up was 24 months. During the study period, six of the children receiving rifabutin prophylaxis for M. avium complex developed unusual bilateral, initially peripheral, stellate, corneal endothelial deposits without associated uveitis. Review of serial corneal drawings and photographs showed an increase in the number of corneal deposits with continued administration of rifabutin. The duration of rifabutin treatment (P = .017) and follow-up (P = .0011) was significantly longer in patients who developed these corneal endothelial changes. CONCLUSION: Corneal endothelial deposits should be considered a potential side effect of rifabutin therapy. To date, these findings have not been sight threatening.

AIDS-Related Opportunistic Infections↗
PubMed1999

Cystoid macular edema after phacoemulsification: relationship to blood-aqueous barrier damage and visual acuity.

PURPOSE: To ascertain the incidence of cystoid macular edema (CME) after phacoemulsification and its relationship to blood-aqueous barrier damage and visual acuity. SETTING: A British teaching hospital. METHODS: A prospective trial was performed to document the incidence of CME after routine phacoemulsification with continuous curvilinear capsulorhexis. LogMAR visual acuity and laser flare were measured using the KOWA FC 1000 laser cell-flare meter preoperatively and 1, 14, 30, and 60 days postoperatively. At day 60, a standardized fluorescein angiogram was performed and graded by masked observers. RESULTS: The rate of angiographic CME on day 60 was 19%. Visual acuity at each visit was significantly worse in the CME group (P < .05). The flare and cell values at days 14, 30, and 60 were higher in the CME group at day 60; however, the difference was not statistically significance (P > .05). CONCLUSIONS: The incidence of CME after routine phacoemulsification was 19%. Patients with CME at day 60 had significantly worse visual acuity than those who did not from the first postoperative day throughout the follow-up. There was a trend for patients who had CME at day 60 to have more postoperative inflammation.

Aged↗
PubMed1999

Use of microdissection and molecular genetics in the pathologic diagnosis of retinoblastoma.

BACKGROUND/PURPOSE: Retinoblastoma results from mutations or loss of both alleles of the retinoblastoma gene. Although retinoblastoma is usually recognized clinically, some forms of the disease can elude diagnosis. The purpose of this study was to determine whether the use of molecular genetics to detect a loss of heterozygosity (LOH) in the retinoblastoma gene could assist the ocular pathologist in the diagnosis of this malignancy. METHODS: Deoxyribonucleic acid (DNA) was obtained from tumor cells microdissected from three ocular specimens from two patients with diffuse retinoblastoma. Polymerase chain reaction was used to detect two microsatellite markers (D13S153 and D13S118) of the retinoblastoma gene. Loss of heterozygosity was identified when one of the two polymorphic alleles was present in the DNA from normal tissue but absent or reduced in the DNA obtained from tumor cells. RESULTS: Loss of heterozygosity was identified in all three specimens from the two patients with diffuse retinoblastoma. In one patient, the diagnosis of retinoblastoma was based on identification of LOH from tumor cells obtained from vitrectomy. CONCLUSIONS: This study demonstrates that identification of LOH in retinoblastoma cells not only can contribute to our understanding of the molecular genetics of this tumor, but also can help the ocular pathologist in the diagnosis of atypical forms of the disease.

Adolescent↗
PubMed1999

Ocular manifestations of HIV infection.

Ophthalmic abnormalities are common in HIV-infected patients. Serious ophthalmic diseases often result from opportunistic infections and can cause blindness in the absence of prompt diagnosis and therapy. We review recent advances in the diagnosis and management of HIV-associated ocular disease, including cytomegalovirus retinitis, the leading cause of vision loss in HIV-infected patients. The widespread use of highly active antiretroviral therapy (HAART) over the past 3 years has reduced the morbidity and mortality associated with HIV infection. HAART has dramatically altered the incidence and natural history of many opportunistic infections, and we discuss the impact of HAART on ophthalmic disease.

AIDS-Related Opportunistic Infections↗