Search PubMed⌕ Search

Biomedical subjects

D A Jabs

Publications and source records attributed to D A Jabs.

At least 55 records · Page 3Linked to original sources
PubMed1997

Role of T cells in the pathogenesis of autoimmune lacrimal gland disease in MRL/Mp-lpr/lpr mice.

PURPOSE: MRL/Mp-lpr/lpr mice (MRL/lpr) spontaneously develop an autoimmune disease, including lacrimal gland lesions, which are a model for Sjögren's syndrome. Target organ lesions in MRL/lpr mice are composed largely of CD4+ T cells, and treatment with monoclonal antibodies (mAb) against CD4 improves in the systemic autoimmune disease but not the lacrimal gland inflammation. In anti-CD4 mAb-treated MRL/lpr mice, the lacrimal gland lesions are composed largely of CD8+ T cells. The effects of depletion of: (1) all T cells; (2) both CD4+ and CD8+ T cells, and (3) only CD8+ T cells on the lacrimal gland disease were investigated. METHODS: MRL/lpr mice underwent neonatal thymectomy and were treated with weekly injections of 6 mg of anti-Thy 1 mAb from age one week until sacrifice at age five months. Control nonthymectomized mice underwent similar treatment with either saline or normal rat immunoglobulin (rIg) injections. In a second experiment, MRL/lpr mice were treated with weekly injections of either: (1) 2 mg anti-CD4 mAb and 5 mg anti-CD8; or (2) 5 mg anti-CD8 alone. Control mice underwent similar treatment with either saline or rIg injections. RESULTS: Combined treatment with neonatal thymectomy and anti-Thy 1 mAb was effective in reducing the lacrimal gland disease in both frequency (50% > or = grade 3 vs. 100% in controls, P < 0.002) and extent (median 0% of lacrimal gland area involved by inflammation vs. 14.8% in controls; P = 0.01). Combined anti-CD4 and anti-CD8 therapy also was effective in reducing the lacrimal gland disease in terms of frequency (25% grade 3 vs. 93% in controls; P = 0.002) and extent (median 0% of lacrimal gland involved by inflammation vs. 12.9% in controls; P = 0.0005). Treatment with anti-CD8 mAb therapy alone was ineffective. The systemic autoimmune disease was also improved by T cell depletion and by combined anti-CD4 and anti-CD8 mAb therapy but not by anti-CD8 mAb therapy alone. CONCLUSIONS: Suppression of both CD4+ and CD8+ T cells is required to suppress lacrimal gland inflammation in MRL/lpr mice.

Animals↗
PubMed1997

T cell subsets and cytomegalovirus retinitis in human immunodeficiency virus-infected patients.

A case-control study was done to investigate the relationship between T cell subsets and cytomegalovirus (CMV) retinitis in human immunodeficiency virus (HIV)-infected subjects with or without CMV retinitis and CD4+ cell counts of <0.050 x 10(9)/L. Cell surface markers on peripheral blood lymphocytes were evaluated using flow cytometry. Patients with CMV retinitis had significantly lower levels of CD8+ cells (median: 0.152 x 10(9)/L) compared with levels for controls (median: 0.296 x 10(9)/L, P < .001). Significant down-regulation of costimulatory molecule CD28+ and lymphocyte function-associated antigen-1 (LFA-1) expression was observed in patients versus controls (CD28+: 0.048 x 10(9)/L vs. 0.143 x 10(9)/L, P < .001; LFA-1: 0.238 x 10(9)/L vs. 0.400 x 10(9)/L, P < .001), but no significant differences were noted for NK cells. We propose that progressive loss of the CD3+ CD8+ cell subset and down-regulation of CD28 and LFA-1 accessory molecules are associated with an increased risk of CMV retinitis in HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1997

Viral resistance and CMV retinitis: design and methods of a prospective study. CRVR Research Groups. Cytomegalovirus Retinitis Viral Resistance Research Group.

A prospective study following a cohort of patients with newly diagnosed, previously untreated cytomegalovirus (CMV) retinitis is being conducted to study drug resistant CMV. Prior to initiation of treatment, patients undergo a baseline eye examination, fundus photography, and blood and urine culture for presence of CMV, and drug susceptibility testing against positive isolates. Patients are followed monthly with a detailed eye examination to diagnose progression of retinitis, and for fundus photography. Cultures are repeated at 1 and 3 months after enrollment, every 3 months thereafter, and at the time of treatment reinduction for the progression of retinitis. This study was designed to determine the prevalence and incidence of drug resistant CMV, as well as risk factors for the development of resistant CMV. It also will determine the correlation between clinical outcome, as measured both by eye examination and fundus photography, and viral resistance.

AIDS-Related Opportunistic Infections↗
PubMed1996

Cytomegalovirus retinitis and viral resistance. Prevalence of resistance at diagnosis, 1994. Cytomegalovirus Retinitis and Viral Resistance Study Group.

OBJECTIVE: To determine the prevalence of cytomegalovirus (CMV) isolates resistant to ganciclovir sodium or foscarnet sodium at the time of diagnosis of CMV retinitis, prior to the initiation of therapy. DESIGN: Prospective epidemiologic study. SETTING: An acquired immunodeficiency syndrome ophthalmology clinic. PATIENTS: Patients with acquired immunodeficiency syndrome and newly diagnosed CMV retinitis. INTERVENTION: Culturing blood and urine samples for CMV and testing of all positive isolates for sensitivity to ganciclovir and foscarnet. MAIN OUTCOME MEASURE: Prevalence of the following: blood culture isolates resistant to ganciclovir (inhibitory concentration 50% [IC50] > 5.5 mumol/L) or foscarnet (IC50 > 400 mumol/L) and urine culture isolates resistant to ganciclovir or foscarnet. RESULTS: Forty-nine patients were enrolled during a 13-month period. Forty-four patients had blood culture samples that could be evaluated; of these, 66% were positive (59% of patients). Thirty-four patients had urine cultures that were evaluable; of these, 82% were positive (57% of patients). Overall, 78% of patients had either a urine or blood culture sample positive for CMV. No blood culture isolates were resistant to ganciclovir, and only 1 urine culture isolate (2% of patients) was resistant to ganciclovir. Three percent of blood culture isolates and 4% of urine culture isolates (2% and 2% of patients, respectively) were resistant to foscarnet. Overall, 4% of patients had either a blood or urine culture isolate resistant to foscarnet. CONCLUSION: Resistance to ganciclovir or foscarnet at the time of diagnosis of CMV retinitis is uncommon.

AIDS-Related Opportunistic Infections↗
PubMed1996

Measuring visual function and quality of life in patients with cytomegalovirus retinitis. Development of a questionnaire. Studies of Ocular Complication of AIDS Research Group.

OBJECTIVE: To develop and test a brief questionnaire designed to assess visual symptoms, visual function in daily activities, and impact of treatment administration in patients with cytomegalovirus retinitis related to acquired immunodeficiency syndrome. DESIGN: Observational cross-sectional study. Patients were recruited in June and July 1992. SETTING: Seven university-based sites participating in the Studies of Ocular Complications of AIDS. PATIENTS: Twenty-six subjects enrolled in a randomized trial that compared foscarnet and ganciclovir for the treatment of cytomegalovirus retinitis. MAIN OUTCOME MEASURES AND ANALYSIS: Distributions of scores, reliability, and validity of newly developed scales to assess visual function, visual symptoms, and global vision. Spearman rank correlations with 95% confidence intervals were used to test hypothesized relationships between scale scores, visual acuity, visual field, and findings from visual examination. RESULTS: The final 18-item self-administered questionnaire required 5 minutes to complete. The new scales had high internal consistency (Cronbach alpha = .81 to .94). As hypothesized, patient-reported vision scores decreased with greater abnormalities found on ophthalmologic examination. Visual symptoms were most strongly related to findings in the worse eye. Visual function and global vision scores were moderately correlated with findings from visual testing and examination, and less strongly related to general health perceptions. Patients reported considerable impairment: 42% reported blurred vision; 40%, difficulty reading; 44%, difficulty driving; and 40%, that treatment interfered with social activities; 50% reported substantial trouble with their vision. CONCLUSIONS: The brief questionnaire developed to assess patient-reported visual function in cytomegalovirus retinitis appears reliable and valid as a measure of performance of vision-related activities, visual symptoms, and the impact of treatment administration. Further research is needed to test its utility as an outcome measure in longitudinal studies of cytomegalovirus retinitis.

AIDS-Related Opportunistic Infections↗
PubMed1996

Design of clinical trials for drug combinations: cytomegalovirus retinitis--foscarnet and ganciclovir. The CMV retinitis retreatment trial.

The Cytomegalovirus Retinitis Retreatment Trial was a multicenter clinical trial designed to evaluate three treatments for the treatment of relapsed CMV retinitis; (1) foscarnet; (2) 'high-dose' ganciclovir, and (3) combination foscarnet and ganciclovir. Two hundred seventy-nine patients were enrolled and randomly assigned to one of these three regimens. Patients were followed monthly for 6 months and every 3 months thereafter. Outcomes of interest included: (1) mortality; (2) retinitis progression; (3) change in retinal area affected by CMV; (4) loss of visual field; (5) loss of visual acuity; (6) quality of life; and (7) treatment side effects.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Clinical features and associated systemic diseases of HLA-B27 uveitis.

PURPOSE: To delineate the clinical features, course, complications, and associated systemic diseases in patients with HLA-B27-associated uveitis. METHODS: We reviewed the records of 148 patients with HLA-B27-associated uveitis from two large uveitis practices. RESULTS: There were 127 (86%) white and 21 (14%) nonwhite patients, and a male-to-female ratio of 1.5:1. The median age at onset of uveitis was 32 years; eight patients (5%) had their first attack after age 55 years. Acute anterior uveitis was noted in 129 patients (87%), and nonacute inflammation was noted in 19 (13%). Ocular involvement was categorized as unilateral or unilateral alternating in 138 patients (93%), but ten patients (7%) had bilateral, concurrent disease. The median duration of an attack was six weeks, and the median number of recurrences for patients with more than 12 months of follow-up was three. Cataracts were associated with posterior synechiae (P = .03), increased intraocular pressure (P = .003), and cystoid macular edema (P = .04). An HLA-B27-associated systemic disorder was present in 83 patients (58%), 30 of whom were women, and it was diagnosed in 43 of the 83 patients as a result of the ophthalmologic consultation. Thirty-four (30%) of 112 patients had a family history of a spondyloarthropathy. CONCLUSIONS: Although HLA-B27-associated uveitis is usually described as a disease of young white men, women and nonwhites may also be affected. A subgroup of patients have severe disease and consequently more complications. Most patients have an associated systemic disease, including women, who appear to have more atypical spondyloarthropathies. The systemic diseases were frequently undiagnosed before the onset of the ocular disease and before the uveitis consultation.

Acute Disease↗
PubMed1996

Ophthalmic complications of HIV infection.

HIV retinopathy, a noninfectious microangiopathy, is the most common ocular manifestation of HIV infection. Opportunistic infections, neoplasms, neuro-ophthalmic lesions, and drug-induced lesions may also cause ocular problems. Opportunistic ocular infections, particularly CMV retinitis, are a major cause of morbidity in patients with AIDS. Because of the underlying chronic and progressive immune dysfunction, the ocular symptoms, signs, clinical course, and treatment are often atypical and severe, requiring protracted medical therapy.

AIDS-Related Opportunistic Infections↗
PubMed1996

Summary of the International Consensus Symposium on Advances in the Diagnosis, Treatment and Prophylaxis and Cytomegalovirus Infection.

CMV infection and CMV disease can be difficult to differentiate and the diagnosis is usually based on a compatible clinical picture and the results of a diagnostic test for CMV. The only exception to this rule is in HIV-infected patients where fundoscopy is sufficient to diagnose CMV retinitis. Of the current diagnostic tests, qualitative and quantitative PCR, branched DNA and Hybrid Capture, are the most promising. The pp65 antigenemia assay has the disadvantage of being more labor-intensive than the DNA based tests. Preliminary data show that a positive qualitative PCR in a HIV-infected patient has a predictive value for the development of CMV retinitis. However, of the patients positive by qualitative PCR, those with high viral loads in quantitative PCR were at the greatest risk of CMV disease. This might make it possible to identify with great certainty the patients who will go on to develop CMV retinitis, thereby decreasing the number of patients eligible for preemptive or prophylactic therapy and increasing the cost-benefit of this therapeutic measure. Quantitative test might also be useful in monitoring response to therapy, but randomized trials comparing the test are needed. Prophylactic antiviral agents should not be used in seronegative transplant recipients receiving organs from seronegative donors. In high-risk transplant recipients, ganciclovir should be used. CMV vaccines are useful for the protection of babies from CMV seronegative mothers against congenital CMV disease. It also may be useful in seronegative transplant recipients receiving a seropositive donor organ, although the benefit of chemo prophylaxis may surpass that of vaccine. HIV-infected patients with CMV retinitis who relapse under either ganciclovir or foscarnet benefit from subsequent combination therapy, rather than switching to the other drug. However, the cost is high in terms of quality of life. Intravitreal therapy for CMV retinitis is very efficacious, suggesting that drug delivery is a problem in systemic therapy. However, intravitreal therapy does not protect against the development of CMV retinitis in the contralateral eye or from CMV disease elsewhere. Therefore, systemic therapy should be added. CMV disease of the CNS should be diagnosed early and treated agressively, possible with combination therapy. A diagnosis of CMV disease should be based on a compatible clinical picture and the demonstration of CMV in CSF by DNA or antigen assays which are more sensitive than culture.

Animals↗
PubMed1996

Antiphospholipid antibodies and retinal vascular disease.

BACKGROUND: Antiphospholipid antibody retinopathy is a rare and poorly defined clinical entity in which the proper diagnosis has important ocular and systemic implications. The clinical course of five patients with antiphospholipid antibody retinopathy is described and the role of such antibodies in idiopathic retinal venous occlusive disease is investigated. METHODS: Five case reports are presented highlighting the presentation, course, therapy, associations and outcomes of patients with antiphospholipid antibody retinopathy. In addition, twenty additional patients presenting with idiopathic retinal venous occlusive disease were tested for the presence of antiphospholipid antibodies. RESULTS: All five patients with antiphospholipid antibody retinopathy had diffuse retinal vascular occlusion. All five patients presented with associated rheumatologic disease, including three with lupus or lupus-like disease. Antibodies to antiphospholipid were not detected in any of the twenty patients with idiopathic retinal venous occlusive disease. Prompt panretinal photocoagulation together with varying regimens of corticosteroids, immunosuppressives, or warfarin was partially successful in stabilizing the ocular and systemic disease. CONCLUSION: The diagnosis of antiphospholipid antibody retinopathy should be suspected in patients with diffuse retinal vaso-occlusion, particularly when characterized by involvement of both arteries and veins, neovascularization at presentation, and symptoms of symptoms of systemic rheumatologic disease. Antiphospholipid antibodies do not appear to play an important role in idiopathic retinal vein occlusions.

Adult↗
PubMed1996

Paradoxic effect of anti-CD4 therapy on lacrimal gland disease in MRL/Mp-lpr/lpr mice.

PURPOSE: MRL/Mp-lpr/lpr mice (MRL/lpr) spontaneously develop lacrimal gland inflammatory lesions and are a model for the human disease Sjögren's syndrome. Therapy with monoclonal antibodies (mAb) to CD4 ameliorates the autoimmune renal, vasculitic, and intraocular inflammatory lesions in MRL/lpr mice. The effect of anti-CD4 mAb therapy on lacrimal gland immunopathology was evaluated. METHODS: From 1 to 5 months of age, MRL/lpr mice were treated with weekly intraperitoneal injections of 2 mg anti-CD4 mAb, after which they were killed and their lacrimal glands were removed for histologic evaluation and immunocytochemistry. Control mice were administered weekly intraperitoneal injections of either saline or normal rat immunoglobulin. RESULTS: Anti-CD4 mAb treatment produced no reduction in lacrimal gland inflammation but did change its morphology. In control mice, there were multiple sharply delineated foci of inflammatory cells in the lacrimal gland, whereas in anti-CD4 mAb-treated mice, there was a more diffuse inflammation surrounding ill-defined foci that spread throughout the gland. Immunocytochemistry revealed that in control mice, lesions were composed predominantly of CD4+ T cells, but in anti-CD4 mAb-treated mice, CD8+ T cells predominated. CONCLUSIONS: Although anti-CD4 mAb therapy of MRL/lpr mice eliminated autoimmune renal disease, autoantibody formation, and ocular inflammatory disease, it had a paradoxic effect on lacrimal gland lesions. Lacrimal gland lesions in the anti-CD4 mAb-treated mice were not decreased, but they had a different morphology and a different immunocytochemical profile.

Animals↗
PubMed1996

Cyclosporine therapy suppresses ocular and lacrimal gland disease in MRL/Mp-lpr/lpr mice.

PURPOSE: MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop an autoimmune disease characterized by lymphoproliferation, vasculitis, glomerulonephritis, autoantibody production, and ocular and lacrimal gland inflammation. Lacrimal gland lesions in MRL/lpr mice are a model for the human disorder Sjögren's syndrome. The target organ lesions in MRL/lpr mice, including those in the eye and lacrimal gland, are composed largely of CD4+ T cells, with lesser numbers of CD8+ T cells and B cells. Cyclosporine therapy was evaluated for its effect on the autoimmune disease, particularly in the eye and lacrimal gland. METHODS: MRL/lpr mice were administered cyclosporine intraperitoneally at a dosage of 2 mg daily from age 1 to 5 months. Animals were killed at 5 months and evaluated for the presence of autoimmune disease. Control groups consisted of animals given daily injections with either saline or the cyclosporine diluent. RESULTS: Cyclosporine therapy was effective in reducing the ocular and lacrimal gland disease. Intraocular inflammation was present in 73% of control animals but in only 15% of cyclosporine-treated animals (P < 0.003). Multifocal lacrimal gland inflammatory infiltrates were present in 100% of controls but in only 23% of cyclosporine-treated animals (P < 0.0001). Mean percent area involved by lacrimal gland inflammation was reduced from 19.7% to 4.7% by cyclosporine therapy (P = 0.0003). Systemic autoimmune disease manifestations, including lymphoproliferation, vasculitis, glomerulonephritis, and serologic abnormalities, also were improved. CONCLUSIONS: Chronic cyclosporine therapy, started at an early age, is effective in controlling the autoimmune disease in MRL/lpr mice, including the ocular and lacrimal gland lesions.

Animals↗