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D A Jabs

Publications and source records attributed to D A Jabs.

At least 37 records · Page 2Linked to original sources

Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel.

PURPOSE: To provide recommendations for the use of immunosuppressive drugs in the treatment of patients with ocular inflammatory disorders. PARTICIPANTS: A 12-person panel of physicians with expertise in ophthalmologic, pediatric, and rheumatologic disease, in research, and in the use of immunosuppressive drugs in patient care. EVIDENCE: Published clinical study results. Recommendations were rated according to the quality and strength of available evidence. PROCESS: The panel was convened in September of 1999 and met regularly through May 2000. Subgroups of the panel summarized and presented available information on specific topics to the full panel; recommendations and ratings were determined by group consensus. CONCLUSIONS: Although corticosteroids represent one of the mainstays in the management of patients with ocular inflammation, in many patients, the severity of the disease, the presence of corticosteroid side effects, or the requirement for doses of systemic corticosteroids highly likely to result in corticosteroid complications supports the rationale for immunosuppressive drugs (for example, antimetabolites, T-cell inhibitors, and alkylating agents) being used in the management of these patients. Because of the potential for side effects, treatment must be individualized and regular monitoring performed. With careful use of immunosuppressive drugs for treatment of ocular inflammatory disorders, many patients will benefit from them either with better control of the ocular inflammation or with a decrease in corticosteroid side effects.

Drug Therapy, Combination↗

Episcleritis and scleritis: clinical features and treatment results.

PURPOSE: To evaluate the clinical experience with episcleritis and scleritis at a tertiary care eye center. METHODS: Retrospective chart review. RESULTS: One hundred thirty-four patients with scleral inflammation were seen over a 12-year period. Thirty-seven patients had episcleritis, and 97 patients had scleritis. Ocular complications occurred in only 13.5% of patients with episcleritis but in 58.8% of patients with scleritis (P <.0001). No patient with episcleritis had a decrease in visual acuity, whereas 15.9% of patients with scleritis did. Only 16.7% of patients with episcleritis required more than topical corticosteroids for treatment, and these patients required oral nonsteroidal anti-inflammatory drugs. Conversely, 30.4% of patients with scleritis required nonsteroidal anti-inflammatory drugs, 31.9% oral prednisone, and 26.1% systemic immunosuppressive drugs (P <.0001). Necrotizing scleritis and posterior scleritis more often were associated with ocular complications, occurring in 91.7% and 85.7%, respectively, than were diffuse anterior scleritis and nodular anterior scleritis (P =.020). Patients with necrotizing scleritis and posterior scleritis were more likely to be treated with oral corticosteroids or immunosuppressive drugs (90% and 100%, respectively) than were patients with diffuse anterior scleritis and nodular anterior scleritis (56.4% and 21.4%, respectively, P =.002). CONCLUSIONS: Scleritis is a severe ocular inflammation, often associated with ocular complications, and nearly always treated with systemic medications. Nearly 60% of these patients will need oral corticosteroids or immunosuppressive drugs to control the disease.

Adolescent↗

Th1 versus Th2 immune responses in autoimmune lacrimal gland disease in MRL/Mp mice.

PURPOSE: In MRL/Mp-lpr/lpr (MRL/lpr) and MRL/Mp-+/+ (MRL/+) mice, a T-cell-driven lacrimal gland inflammation spontaneously develops that is a model for Sjögren's syndrome. The lacrimal gland lesions in these mice were evaluated by immunohistochemistry for the relative contributions of T-helper (Th)1 versus Th2 immune responses. METHODS: Frozen sections of lacrimal glands from MRL/lpr and MRL/+ mice ages 1 through 5 months were stained with monoclonal antibodies to the cytokines interferon (IFN)-gamma and interleukin (IL)4 and to the cell surface costimulatory molecules B7-1 and B7-2, which are associated with Th1 and Th2 responses, respectively. RESULTS: The median proportion of cells staining for IL-4 ranged from 30% to 67% over time for MRL/lpr mice and from 30% to 55% for MRL/+ mice. The median proportion of cells staining for IFN-gamma ranged from 1% to 5% for MRL/lpr mice and from 0% to 3% for MRL/+ mice. The proportion of cells staining positively for IL-4 was significantly greater than for IFN-gamma in both MRL/lpr (mean difference, 33%; P = 0.0001) and MRL/+ mice (mean difference, 42%; P = 0.0002). The median proportion of cells staining positively for B7-2 ranged from 20% to 38% for MRL/lpr mice and from 16% to 34% for MRL/+ mice. The median proportion of cells staining for B7-1 ranged from 2% to 10% for MRL/lpr mice and from 2% to 5% for MRL/+ mice. The proportion of cells staining positively for B7-2 was significantly greater than for B7-1 for both MRL/lpr mice (mean difference, 15%; P = 0.001) and for MRL/+ mice (mean difference, 19%; P = 0.006). CONCLUSIONS: On the basis of immunohistochemistry for cytokines and costimulatory molecules, inflammatory lacrimal gland lesions in MRL/lpr and MRL/+ mice appear to be a largely Th2 phenomenon.

Animals↗

Pars planitis: clinical features and class II HLA associations.

OBJECTIVE: To describe a cohort of patients with pars planitis followed at a single tertiary care institution, determine the frequency of multiple sclerosis and/or optic neuritis in patients with this disorder, and calculate gene frequencies of human leukocyte antigen (HLA) class II alleles in these patients. DESIGN: Fifty-three patients with the diagnosis of pars planitis underwent clinical record review or telephone interview for follow-up or both; 32 of these underwent phlebotomy for analysis of HLA class II alleles. MAIN OUTCOME MEASURES: Outcomes included visual acuity, occurrence of multiple sclerosis and/or optic neuritis, and HLA class II gene frequencies. RESULTS: With a mean follow-up of 2 years, approximately 90% of patients maintained a visual acuity better than 20/40 in at least one eye. The most frequently encountered ophthalmic complications included cystoid macular edema, cataract, and epiretinal membrane formation. Of 37 patients with pars planitis who had medical or neurologic follow-up evaluations, 6 (16.2%) developed multiple sclerosis. The HLA-DR15 allele, coding for one of the two HLA-DR2 subtypes, was associated with pars planitis (odds ratio = 2.86, 95% confidence interval = 1.42-5.78, P = 0.004). CONCLUSIONS: A common immunogenetic predisposition to multiple sclerosis and pars planitis may be associated with the HLA-DR15 allele. This association may represent genetic linkage to the HLA-DR locus or a role for the HLA-DR15 gene product in the pathogenesis of both of these diseases.

Adolescent↗

Comparison of cytomegalovirus loads in plasma and leukocytes of patients with cytomegalovirus retinitis. The Cytomegalovirus Retinitis and Viral Resistance Study Group.

Cytomegalovirus (CMV) DNA loads in paired leukocyte and plasma samples from 199 patient visits by 66 patients with CMV retinitis were determined. Leukocyte CMV load determinations had a greater range of values (mean, 24,587 copies/10(6) leukocytes; maximum, 539, 000) than did plasma CMV load determinations (mean, 10,302 copies/ml; maximum, 386,000), and leukocyte viral loads were detectable in a greater proportion of patients at the time of diagnosis of CMV retinitis prior to initiation of anti-CMV therapy (82%) than were plasma viral loads (64%) (P = 0.0078). Agreement with CMV blood cultures was slightly better for plasma (kappa = 0. 68) than for leukocytes (kappa = 0.53), due to a greater proportion of patients with detectable viral loads in leukocytes having negative blood cultures.

Cytomegalovirus↗

Catheter complications in AIDS patients treated for cytomegalovirus retinitis.

PURPOSE: To describe the complications of central venous catheter use for intravenous therapy of cytomegalovirus (CMV) retinitis in patients with AIDS. METHODS: Retrospective review of 388 patients with AIDS and CMV retinitis treated with intravenous medications through an indwelling catheter. RESULTS: The catheter complication rate was 1.2 complications per person-year (0.33 complications per 100 catheter-days). Current injecting drug use increased the risk of infectious complications [hazard ratio (HR), 1.73; P=0.04] whereas former use did not (HR, 0.96; P=0.88). Subdermal port catheters increased the risk of bacteremia (HR, 1.78; P=0.05). Mortality for the first complication was 5.8%. Forty percent of patients required catheter removal, and 86.8% of these patients required reinsertion of another catheter. CONCLUSIONS: Catheter complications are a substantial problem in patients with CMV retinitis treated with daily intravenous therapy.

AIDS-Related Opportunistic Infections↗

Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel. International AIDS Society-USA.

OBJECTIVE: To provide recommendations for the treatment of acquired immunodeficiency syndrome-related cytomegalovirus (CMV) end-organ diseases, including retinitis, colitis, pneumonitis, and neurologic diseases. PARTICIPANTS: A 17-member panel of physicians with expertise in clinical and virological research and inpatient care in the field of CMV diseases. EVIDENCE: Available clinical and virological study results. Recommendations are rated according to the quality and strength of available evidence. Recommendations were limited to the treatment of CMV diseases; prophylaxis recommendations are not included. PROCESS: The panel was convened in February 1997 and met regularly through November 1997. Subgroups of the panel summarized and presented available information on specific topics to the full panel; recommendations and ratings were determined by group consensus. CONCLUSIONS: Although the epidemiological features of CMV diseases are changing in the setting of potent, combination antiretroviral therapy, continued attention must be paid to CMV diseases in patients infected with the human immunodeficiency virus to prevent irreversible endorgan dysfunction. The initial and maintenance treatment of CMV retinitis must be individualized based on the characteristics of the lesions, including location and extent, specific patient factors, and characteristics of available therapies among others. Management of relapse or refractory retinitis must be likewise individualized. Ophthalmologic screening for patients at high risk for retinitis or who have a prior diagnosis of extraretinal disease is recommended. Recommendations for gastrointestinal, pulmonary, and neurologic manifestations are included.

AIDS-Related Opportunistic Infections↗

Cytomegalovirus retinitis and viral resistance: 3. Culture results. CMV Retinitis and Viral Resistance Study Group.

PURPOSE: To evaluate the relationship between blood and urine cultures for cytomegalovirus and clinical outcomes in patients with cytomegalovirus retinitis. METHODS: Prospective epidemiologic study of 108 patients with newly diagnosed cytomegalovirus retinitis. Blood and urine were cultured for cytomegalovirus at diagnosis of retinitis, at 1 month and 3 months after diagnosis, and every 3 months thereafter. RESULTS: Of the patients, 80.6% were found to have either a positive blood culture or urine culture for cytomegalovirus at the time of diagnosis of retinitis, and a positive blood culture at diagnosis was associated with an increased mortality (odds ratio = 1.91, P = .012). Follow-up cultures were positive in approximately 20% of patients, and the rate was constant over time. The development of a positive blood or urine culture during follow-up correlated with the occurrence of cytomegalovirus retinitis in the contralateral eye in those patients with unilateral disease at diagnosis (odds ratio = 5.74, P = .001). CONCLUSIONS: Patients with cytomegalovirus retinitis and positive blood cultures for cytomegalovirus have a poorer prognosis.

AIDS-Related Opportunistic Infections↗

Discontinuing anticytomegalovirus therapy in patients with immune reconstitution after combination antiretroviral therapy.

PURPOSE: To describe our experience with discontinuation of anticytomegalovirus maintenance therapy in patients who have had immune reconstitution after initiation of highly active antiretroviral therapy. METHODS: Fifteen patients with treated cytomegalovirus retinitis, who had immune reconstitution after initiation of highly active retroviral therapy, had anticytomegalovirus maintenance therapy discontinued. Patients were followed closely for relapse of retinitis. RESULTS: Median nadir CD4+ T-cell count, before institution of highly active antiretroviral therapy, was 20 cells/microl. At the time of discontinuation of anticytomegalovirus therapy, median CD4+ T-cell count was 297 cells/microl. Patients were followed for a median of 8 months off anticytomegalovirus therapy (range, 3 to 16 months). The median CD4+ T-cell count at last follow-up was 267 cells/microl. No patient off anticytomegalovirus therapy relapsed. CONCLUSION: In selected patients with immune reconstitution after initiation of highly active antiretroviral therapy, anticytomegalovirus therapy may be safely discontinued, at least temporarily. Longer follow-up of these patients is needed to determine how long such therapy may be interrupted, and when anticytomegalovirus therapy should be reinstituted.

AIDS-Related Opportunistic Infections↗

Summary of the II International Symposium on Cytomegalovirus.

Human cytomegalovirus (HCMV) is a highly species-specific DNA virus belonging to the Betaherpesvirinae subfamily of the herpesviridae family. Like other herpesviruses, primary infection with HCMV is followed by persistence of the virus in a latent form. The sites of latency are still largely undefined, but they probably include bone marrow progenitor cells and peripheral blood monocytes. From these sites, the virus can reactivate, resulting in renewed shedding of the virus, or, in immunocompromized persons, development of disease. Humans are the only reservoir of HCMV and transmission occurs by person-to-person contact. Infection with HCMV is common. In most developed countries, HCMV seroprevalence steadily increases after infancy and 10-20% of children are infected before puberty. In adults, the prevalence of antibodies ranges from 40 to 100%. Although HCMV has a world-wide distribution, infection with HCMV is more common in the developing countries and in areas of low socioeconomic conditions, which is predominantly related to the closeness of contacts within these populations. Except for a mononucleosis-like illness in some persons, infection with HCMV rarely causes disease in immunocompetent individuals. However, HCMV can cause severe morbidity and mortality in congenitally infected newborns and immunocompromized patients, most notably transplant-recipients and HIV-infected persons. This article provides a review of the information presented at the Second International Symposium on Cytomegalovirus organized and convened by The Macrae Group (New York City, NY) in Acapulco, Mexico on 24-28 April 1998. During this symposium, the state-of-the-art knowledge on diagnosis, treatment and prophylaxis of HCMV infections were discussed, and, based on this information, attempts to highlight the future directions in basic and clinical research areas that need to be stimulated to facilitate advancement in prevention and treatment of CMV disease.

AIDS-Related Opportunistic Infections↗

Cytomegalovirus retinitis and viral resistance: ganciclovir resistance. CMV Retinitis and Viral Resistance Study Group.

Cytomegalovirus (CMV) retinitis is among the most common opportunistic infections in patients with AIDS and a substantial cause of visual loss. With long-term therapy, resistant CMV may develop. In a prospective study of 108 patients with CMV retinitis, 80.6% of patients were found to have either a positive blood culture or positive urine culture for CMV at the diagnosis of retinitis. At diagnosis of retinitis, 0.9% and 2.7% of patients had a ganciclovir-resistant blood culture isolate and urine culture isolate, respectively. Of 76 patients initially treated with ganciclovir, 11.4% had a resistant blood or urine culture isolate by 6 months of treatment and 27.5% by 9 months. The development of ganciclovir resistance during follow-up correlated with the occurrence of CMV retinitis in the contralateral eye (odds ratio = 9.06, P = .003).

AIDS-Related Opportunistic Infections↗

Incidence of foscarnet resistance and cidofovir resistance in patients treated for cytomegalovirus retinitis. The Cytomegalovirus Retinitis and Viral Resistance Study Group.

Cytomegalovirus (CMV) retinitis is a common opportunistic infection in patients with AIDS. With long-term therapy for CMV retinitis, resistant CMV may develop. In a prospective study of 122 patients with CMV retinitis, 2.4 and 0.8% of patients had foscarnet-resistant blood culture isolates (50% inhibitory concentration [IC50], >400 microM) and urine culture isolates, respectively, at diagnosis of CMV retinitis prior to treatment, whereas 4.1 and 6.6% had cidofovir-resistant (IC50, >2 microM) blood and urine culture isolates, respectively. Patients were treated according to best medical judgement. Of 44 foscarnet-treated patients, 26% had a resistant blood or urine culture isolate by 6 months of treatment and 37% had a resistant isolate by 9 months; of 13 cidofovir-treated patients, 29% had a resistant blood or urine culture isolate by 3 months of therapy. The probabilities of developing foscarnet resistance while on foscarnet and developing cidofovir resistance while on cidofovir were not significantly different from that for developing ganciclovir resistance while on ganciclovir (odds ratios, 1.87 [P = 0.19] and 2.28 [P = 0.15], respectively).

Adult↗

Pharmacoeconomic analysis of 3 treatment strategies for cytomegalovirus retinitis in patients with AIDS.

A decision-analytical simulation model was constructed to perform a pharmacoeconomic analysis of the following 3 treatment strategies for previously untreated cytomegalovirus (CMV) retinitis in patients with AIDS: (i) intravenous foscarnet (IVF) for induction and maintenance therapy; (ii) intravenous ganciclovir (IVG) for induction and maintenance therapy; and (iii) intravenous ganciclovir for induction therapy, followed by oral ganciclovir for maintenance therapy (IVG-ORG). Patients who experienced significant adverse effects during, or who failed, initial therapy were switched once to one of the other 2 treatments. The model was used to estimate the direct medical cost (from the perspective of a public payer), survival, and survival adjusted for disutility because of lost vision, for each strategy in the first year following treatment initiation. The expected first-year costs of treatment initiated with IVF, IVG and IVG-ORG were $US47,918, $US38,817 and $US32,036 (1994 values), respectively, while expected first-year survival was 41 weeks, 35 weeks and 35 weeks, respectively. The incremental cost per incremental year of survival using IVF was $US78,000 versus IVG and $US138,000 versus IVG-ORG before adjustment for lost vision, and $US93,000 versus IVG and $US166,000 versus IVG-ORG after adjustment for lost vision. About 23% of the cost of the IVG treatment strategy was attributable to treatment-related adverse events, compared with 14% of the cost of IVF and 16% of the cost of IVG-ORG. Because of the high failure rate with IVG-ORG, initial treatment with IVG-ORG frequently led to switching to another treatment. Only 27% of the costs associated with the IVG-ORG treatment strategy were in fact attributable to the cost of induction and maintenance therapy prior to a switch to alternative treatment. In this analysis, initial treatment with IVG-ORG was the least costly approach for treating CMV retinitis in patients with AIDS. Initial treatment with IVF resulted in slightly longer survival adjusted for vision-related quality of life. New treatments for AIDS may reduce the survival benefit of initial treatment with IVF.

Acquired Immunodeficiency Syndrome↗

Syphilitic uveitis in human immunodeficiency virus-infected patients.

OBJECTIVE: To document the incidence and clinical features of syphilitic uveitis in patients coinfected with human immunodeficiency virus (HIV). DESIGN: Retrospective chart review. SETTINGS: Single tertiary uveitis referral center. PATIENTS: The charts of HIV-infected patients with uveitis and a reactive fluorescent treponemal antibody absorption test seen between November 1983 and June 1995 were reviewed. RESULTS: Syphilis was the most common bacterial cause of uveitis in this group. Thirteen patients (0.6% of the 2085 HIV-positive patients seen in the clinic during the study period) were dually infected. Twelve patients were male. Six patients (46%) had previously been treated for syphilis, 4 with intramuscular penicillin G benzathine only. Four patients (31%) had isolated anterior uveitis, 3 patients (23%) had anterior and intermediate uveitis, and 5 patients (38%) had panuveitis. One patient (8%) presented with optic nerve and retinal atrophy. Eight patients were treated with intravenous penicillin, 3 with intravenous and intramuscular penicillin, and 1 with intravenous ceftriaxone sodium. Of the 12 patients for whom follow-up examinations were available after treatment, ocular inflammation decreased in 11 (92%) and visual acuity improved in 8 (67%). Rapid plasma reagin titers decreased a median of 64-fold compared with pretreatment levels, and all patients with reactive cerebrospinal fluid who underwent pretreatment and posttreatment lumbar punctures normalized following therapy with intravenous antibiotics. CONCLUSIONS: Syphilis is an uncommon cause of uveitis in HIV-infected patients. Anterior uveitis is the most common ocular manifestation, but panuveitis is more common than isolated anterior uveitis. Intravenous penicillin is effective therapy.

Adult↗

Cidofovir.

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Antiviral Agents↗